Trial Outcomes & Findings for An Exploratory Study of Nesiritide in Participants With Acute Heart Failure (NCT NCT00490724)

Last Updated: 2014-02-03

Results Overview

Change in PCWP was unmeasurable, therefore it was complemented with PADP. PCWP was measured by pulmonary artery catheterization and provided an indirect measure of left atrial pressure.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

67 participants

Primary outcome timeframe

Baseline and 3 Hours

Results posted on

2014-02-03

Participant Flow

67 participants provided consent, out of these 61 participants were assigned to the study treatment.

Participant milestones

Participant milestones
Measure	Nesiritide (1+ 0.01) Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.
Period I STARTED	21	20	20
Period I COMPLETED	21	20	19
Period I NOT COMPLETED	0	0	1
Period II STARTED	21	20	19
Period II COMPLETED	18	19	16
Period II NOT COMPLETED	3	1	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Nesiritide (1+ 0.01) Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.
Period I Physician Decision	0	0	1
Period II Treatment Discontinuation	3	1	3

Baseline Characteristics

An Exploratory Study of Nesiritide in Participants With Acute Heart Failure

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nesiritide (1+ 0.01) n=19 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) n=20 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) n=17 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.	Total n=56 Participants Total of all reporting groups
Age, Continuous	71.1 Years STANDARD_DEVIATION 14.1 • n=5 Participants	67.5 Years STANDARD_DEVIATION 13.5 • n=7 Participants	64.9 Years STANDARD_DEVIATION 11.6 • n=5 Participants	67.9 Years STANDARD_DEVIATION 13.2 • n=4 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	6 Participants n=7 Participants	7 Participants n=5 Participants	21 Participants n=4 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	14 Participants n=7 Participants	10 Participants n=5 Participants	35 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and 3 Hours

Population: The per protocol set (PPS) included participants who met the eligibility criteria, received at least 1 dose of study medication and had one efficacy assessment after randomization except those who had significant protocol deviations.

Change in PCWP was unmeasurable, therefore it was complemented with PADP. PCWP was measured by pulmonary artery catheterization and provided an indirect measure of left atrial pressure.

Outcome measures

Outcome measures
Measure	Nesiritide (1+ 0.01) n=19 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) n=20 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) n=17 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP or Pulmonary Arterial Diastolic Pressure[PADP]) at 3 Hours Baseline	27.7 Millimeters of Mercury (mmHg) Standard Deviation 8.2	24.8 Millimeters of Mercury (mmHg) Standard Deviation 6.3	29.7 Millimeters of Mercury (mmHg) Standard Deviation 6.6
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP or Pulmonary Arterial Diastolic Pressure[PADP]) at 3 Hours Change at 3 hours	-6.7 Millimeters of Mercury (mmHg) Standard Deviation 5.8	-5.4 Millimeters of Mercury (mmHg) Standard Deviation 6.3	-6.2 Millimeters of Mercury (mmHg) Standard Deviation 6.8

SECONDARY outcome

Timeframe: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 15 and 24 Hour

Population: The PPS included participants who met the eligibility criteria, received at least 1 dose of study medication and had one efficacy assessment after randomization except those who had significant protocol deviations. Here, N=the participants evaluated for this measure and n=the participants evaluated for this measure at a particular time point.

The MRAP was a measured hemodynamic parameter. MRAP was measured using a Swan-Ganz catheter.

Outcome measures

Outcome measures
Measure	Nesiritide (1+ 0.01) n=19 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) n=18 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) n=16 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.
Change From Baseline in Mean Right Atrial Pressure (MRAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 15 and 24 Hour Baseline (n=19,18,16)	14.5 Millimeters of mercury Standard Deviation 9.0	10.3 Millimeters of mercury Standard Deviation 6.8	13.1 Millimeters of mercury Standard Deviation 6.2
Change From Baseline in Mean Right Atrial Pressure (MRAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 15 and 24 Hour Change at 0.25 hour (n=19,17,16)	-1.9 Millimeters of mercury Standard Deviation 3.4	-2.5 Millimeters of mercury Standard Deviation 3.0	-2.6 Millimeters of mercury Standard Deviation 2.4
Change From Baseline in Mean Right Atrial Pressure (MRAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 15 and 24 Hour Change at 0.5 hour (n=19,18,16)	-2.6 Millimeters of mercury Standard Deviation 4.0	-3.1 Millimeters of mercury Standard Deviation 3.2	-3.4 Millimeters of mercury Standard Deviation 2.7
Change From Baseline in Mean Right Atrial Pressure (MRAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 15 and 24 Hour Change at 1 hour (n=19,18,16)	-3.6 Millimeters of mercury Standard Deviation 3.5	-2.7 Millimeters of mercury Standard Deviation 3.4	3.6 Millimeters of mercury Standard Deviation 3.4
Change From Baseline in Mean Right Atrial Pressure (MRAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 15 and 24 Hour Change at 1.5 hour (n=19,18,16)	-3.8 Millimeters of mercury Standard Deviation 6.3	-3.4 Millimeters of mercury Standard Deviation 4.5	-3.8 Millimeters of mercury Standard Deviation 3.3
Change From Baseline in Mean Right Atrial Pressure (MRAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 15 and 24 Hour Change at 2 hour (n=19,18,16)	-4.3 Millimeters of mercury Standard Deviation 6.2	-2.8 Millimeters of mercury Standard Deviation 4.3	-3.4 Millimeters of mercury Standard Deviation 3.8
Change From Baseline in Mean Right Atrial Pressure (MRAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 15 and 24 Hour Change at 2.5 hour(n=19,18,16)	-4.2 Millimeters of mercury Standard Deviation 4.7	-2.5 Millimeters of mercury Standard Deviation 4.1	-3.2 Millimeters of mercury Standard Deviation 4.9
Change From Baseline in Mean Right Atrial Pressure (MRAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 15 and 24 Hour Change at 3 hour (n=19,18,16)	-4.4 Millimeters of mercury Standard Deviation 5.5	-2.5 Millimeters of mercury Standard Deviation 3.7	-2.9 Millimeters of mercury Standard Deviation 4.7
Change From Baseline in Mean Right Atrial Pressure (MRAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 15 and 24 Hour Change at 4 hour (n=19,17,16)	-4.9 Millimeters of mercury Standard Deviation 4.8	-2.0 Millimeters of mercury Standard Deviation 4.2	-2.9 Millimeters of mercury Standard Deviation 6.0
Change From Baseline in Mean Right Atrial Pressure (MRAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 15 and 24 Hour Change at 5 hour (n=18,17,16)	-5.0 Millimeters of mercury Standard Deviation 5.1	-3.0 Millimeters of mercury Standard Deviation 4.6	-2.9 Millimeters of mercury Standard Deviation 7.1
Change From Baseline in Mean Right Atrial Pressure (MRAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 15 and 24 Hour Change at 6 hour (n=18,17,16)	-5.1 Millimeters of mercury Standard Deviation 4.8	-3.3 Millimeters of mercury Standard Deviation 3.7	-3.1 Millimeters of mercury Standard Deviation 6.9
Change From Baseline in Mean Right Atrial Pressure (MRAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 15 and 24 Hour Change at 12 hour (n=17,17,16)	-5.9 Millimeters of mercury Standard Deviation 6.7	-3.4 Millimeters of mercury Standard Deviation 3.2	-4.3 Millimeters of mercury Standard Deviation 4.2
Change From Baseline in Mean Right Atrial Pressure (MRAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 15 and 24 Hour Change at 15 hour (n=2,1,0)	1.0 Millimeters of mercury Standard Deviation 2.8	-3.5 Millimeters of mercury Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	NA Millimeters of mercury Standard Deviation NA No participant was analyzed for this time point
Change From Baseline in Mean Right Atrial Pressure (MRAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 15 and 24 Hour Change at 24 hour (n=14,17,14)	-5.2 Millimeters of mercury Standard Deviation 4.6	-4.5 Millimeters of mercury Standard Deviation 4.7	-5.0 Millimeters of mercury Standard Deviation 5.3

SECONDARY outcome

Timeframe: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour

Population: The PPS included participants who met the eligibility criteria, received at least 1 dose of study medication and had one efficacy assessment after randomization except those who had significant protocol deviations. Here, n=the participants evaluated for this measure at a particular time point.

The PASP was a measured hemodynamic parameters. PASP was assessed by Swan-Ganz catheter.

Outcome measures

SECONDARY outcome

Timeframe: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour

Population: The PPS included participants who met the eligibility criteria, received at least 1 dose of study medication and had one efficacy assessment after randomization except those who had significant protocol deviations. Here, n=the participants evaluated for this measure at a particular time point.

The PADP was a measured hemodynamic parameter. Normal range of PADP is 8 to 15 millimeters of mercury (mmHg). PADP was assessed by Swan-Ganz catheter.

Outcome measures

SECONDARY outcome

Timeframe: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour

Population: The PPS included participants who met the eligibility criteria, received at least 1 dose of study medication and had one efficacy assessment after randomization except those who had significant protocol deviations. Here, n=the participants evaluated for this measure at a particular time point.

The MPAP was a measured hemodynamic parameter. MPAP was measured using a Swan-Ganz catheter.

Outcome measures

SECONDARY outcome

Timeframe: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour

The PCWP was a measured hemodynamic parameter. It was the blood pressure, recorded after wedging a catheter in a small pulmonary artery; believed to reflect the pressure in the pulmonary capillaries. It was measured by pulmonary artery catheterization and provided an indirect measure of left atrial pressure.

Outcome measures

SECONDARY outcome

Timeframe: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour

Population: The PPS included participants who met the eligibility criteria, received at least 1 dose of study medication and had one efficacy assessment after randomization except those who had significant protocol deviations. Here, n=the participants evaluated for this measure at a particular time point.

The CO was a measured cardiopulmonary hemodynamic parameter. It is the volume of blood expelled by the ventricles of the heart with each beat. It was calculated as the product of stroke volume (output of either ventricle per heartbeat) and the number of beats per minute. Cardiac output is commonly measured by the thermodilution technique.

Outcome measures

Outcome measures
Measure	Nesiritide (1+ 0.01) n=19 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) n=20 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) n=17 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.
Change From Baseline in Cardiac Output (CO) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Baseline (n=19,20,17)	4.4026 Liter per minute Standard Deviation 1.4463	3.9768 Liter per minute Standard Deviation 1.2767	4.0971 Liter per minute Standard Deviation 1.4259
Change From Baseline in Cardiac Output (CO) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 0.25 hour (n=19,19,17)	0.2947 Liter per minute Standard Deviation 0.7227	0.5686 Liter per minute Standard Deviation 0.7616	0.2912 Liter per minute Standard Deviation 0.9378
Change From Baseline in Cardiac Output (CO) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 0.5 hour (n=19,20,17)	0.3721 Liter per minute Standard Deviation 0.6143	0.8102 Liter per minute Standard Deviation 0.9328	1.4147 Liter per minute Standard Deviation 1.2028
Change From Baseline in Cardiac Output (CO) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 1 hour (n=19,20,17)	0.3668 Liter per minute Standard Deviation 0.9398	0.7838 Liter per minute Standard Deviation 0.7643	1.1382 Liter per minute Standard Deviation 0.6744
Change From Baseline in Cardiac Output (CO) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 1.5 hour (n=19,20,17)	0.2795 Liter per minute Standard Deviation 1.1145	0.5947 Liter per minute Standard Deviation 1.1077	0.7206 Liter per minute Standard Deviation 1.0939
Change From Baseline in Cardiac Output (CO) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 2 hour (n=19,20,17)	0.3026 Liter per minute Standard Deviation 1.3596	0.3497 Liter per minute Standard Deviation 1.0715	0.3500 Liter per minute Standard Deviation 0.7163
Change From Baseline in Cardiac Output (CO) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 2.5 hour (n=19,20,17)	-0.3105 Liter per minute Standard Deviation 1.1770	0.0292 Liter per minute Standard Deviation 0.6977	0.3029 Liter per minute Standard Deviation 0.9547
Change From Baseline in Cardiac Output (CO) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 3 hour (n=19,20,17)	0.0095 Liter per minute Standard Deviation 1.0695	0.1597 Liter per minute Standard Deviation 0.7112	-0.0265 Liter per minute Standard Deviation 0.8170
Change From Baseline in Cardiac Output (CO) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 4 hour (n=19,19,17)	-0.2742 Liter per minute Standard Deviation 0.9836	0.1435 Liter per minute Standard Deviation 0.7650	0.1912 Liter per minute Standard Deviation 0.5167
Change From Baseline in Cardiac Output (CO) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 5 hour (n=18,19,17)	-0.3356 Liter per minute Standard Deviation 1.2717	0.1472 Liter per minute Standard Deviation 0.6739	0.2676 Liter per minute Standard Deviation 0.9761
Change From Baseline in Cardiac Output (CO) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 6 hour (n=18,19,17)	-0.5706 Liter per minute Standard Deviation 1.4351	-0.1994 Liter per minute Standard Deviation 0.6581	0.1735 Liter per minute Standard Deviation 1.0341
Change From Baseline in Cardiac Output (CO) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 9 hour (n=0,1,0)	NA Liter per minute Standard Deviation NA No participant was analyzed for this time point	0.3500 Liter per minute Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	NA Liter per minute Standard Deviation NA No participant was analyzed for this time point
Change From Baseline in Cardiac Output (CO) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 12 hour (n=16,19,17)	-0.5453 Liter per minute Standard Deviation 0.8935	-0.3177 Liter per minute Standard Deviation 0.6534	0.2853 Liter per minute Standard Deviation 1.2070
Change From Baseline in Cardiac Output (CO) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 15 hour (n=2,1,0)	-0.4500 Liter per minute Standard Deviation 0.5657	0.3000 Liter per minute Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	NA Liter per minute Standard Deviation NA No participant was analyzed for this time point
Change From Baseline in Cardiac Output (CO) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 24 hour (n=14,19,15)	-0.1246 Liter per minute Standard Deviation 1.1352	-0.3108 Liter per minute Standard Deviation 0.8702	-0.3200 Liter per minute Standard Deviation 1.1894

SECONDARY outcome

Timeframe: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 Hour

Population: The PPS included participants who met the eligibility criteria, received at least 1 dose of study medication and had one efficacy assessment after randomization except those who had significant protocol deviations. Here, n=the participants evaluated for this measure at a particular time point.

The MBP was a calculated hemodynamic parameter and the calculation was done on the basis of the measured hemodynamic parameters. MBP was calculated as sum of diastolic blood pressure (DBP) and (0.33\*\[SBP-DBP\])

Outcome measures

SECONDARY outcome

Timeframe: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour

Population: The PPS included participants who met the eligibility criteria, received at least 1 dose of study medication and had one efficacy assessment after randomization except those who had significant protocol deviations. Here, n=the participants evaluated for this measure at a particular time point.

The CI was a calculated hemodynamic parameter and the calculation was done on the basis of the measured hemodynamic parameters. CI was calculated by dividing CO and body surface area.

Outcome measures

SECONDARY outcome

Timeframe: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour

The SV was a calculated hemodynamic parameter and the calculation was done on the basis of the measured hemodynamic parameters. Stroke volume is the volume of blood ejected from a ventricle at each beat of the heart, equal to the difference between the end-diastolic volume and the end-systolic volume. SV was calculated by dividing CO and heart rate (HR).

Outcome measures

Outcome measures
Measure	Nesiritide (1+ 0.01) n=17 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) n=19 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) n=17 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.
Change From Baseline in Stroke Volume (SV) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 24 hour (n=13,18,15)	2.333 milliliter (ml) Standard Deviation 16.239	-1.421 milliliter (ml) Standard Deviation 14.266	0.448 milliliter (ml) Standard Deviation 11.288
Change From Baseline in Stroke Volume (SV) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Baseline (n=17,19,17)	48.368 milliliter (ml) Standard Deviation 18.272	49.126 milliliter (ml) Standard Deviation 22.030	41.545 milliliter (ml) Standard Deviation 12.290
Change From Baseline in Stroke Volume (SV) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 0.25 hour (n=17,19,17)	4.122 milliliter (ml) Standard Deviation 9.604	3.305 milliliter (ml) Standard Deviation 7.556	3.517 milliliter (ml) Standard Deviation 8.589
Change From Baseline in Stroke Volume (SV) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 0.5 hour (n=17,19,17)	6.348 milliliter (ml) Standard Deviation 8.940	6.887 milliliter (ml) Standard Deviation 11.497	15.121 milliliter (ml) Standard Deviation 13.429
Change From Baseline in Stroke Volume (SV) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 1 hour (n=17,19,17)	6.295 milliliter (ml) Standard Deviation 9.587	8.442 milliliter (ml) Standard Deviation 8.368	13.039 milliliter (ml) Standard Deviation 7.426
Change From Baseline in Stroke Volume (SV) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 1.5 hour (n=17,19,17)	4.666 milliliter (ml) Standard Deviation 11.659	7.722 milliliter (ml) Standard Deviation 12.452	8.293 milliliter (ml) Standard Deviation 9.497
Change From Baseline in Stroke Volume (SV) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 2 hour (n=17,19,17)	6.003 milliliter (ml) Standard Deviation 14.727	6.877 milliliter (ml) Standard Deviation 15.550	6.119 milliliter (ml) Standard Deviation 8.270
Change From Baseline in Stroke Volume (SV) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 2.5 hour (n=17,19,17)	0.133 milliliter (ml) Standard Deviation 12.357	1.768 milliliter (ml) Standard Deviation 11.073	5.490 milliliter (ml) Standard Deviation 9.857
Change From Baseline in Stroke Volume (SV) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 3 hour (n=17,19,17)	4.744 milliliter (ml) Standard Deviation 12.370	2.865 milliliter (ml) Standard Deviation 8.973	2.909 milliliter (ml) Standard Deviation 8.238
Change From Baseline in Stroke Volume (SV) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 4 hour (n=17,18,17)	1.477 milliliter (ml) Standard Deviation 10.205	2.888 milliliter (ml) Standard Deviation 9.530	5.053 milliliter (ml) Standard Deviation 5.633
Change From Baseline in Stroke Volume (SV) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 5 hour (n=16,18,17)	0.909 milliliter (ml) Standard Deviation 16.362	4.339 milliliter (ml) Standard Deviation 8.641	6.802 milliliter (ml) Standard Deviation 9.925
Change From Baseline in Stroke Volume (SV) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 6 hour (n=16,18,17)	-0.391 milliliter (ml) Standard Deviation 15.734	2.685 milliliter (ml) Standard Deviation 13.448	5.544 milliliter (ml) Standard Deviation 9.810
Change From Baseline in Stroke Volume (SV) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 9 hour (n=0,1,0)	NA milliliter (ml) Standard Deviation NA No participant was analyzed for this time point	8.792 milliliter (ml) Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	NA milliliter (ml) Standard Deviation NA No participant was analyzed for this time point
Change From Baseline in Stroke Volume (SV) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 12 hour (n=15,18,17)	1.254 milliliter (ml) Standard Deviation 13.051	-1.357 milliliter (ml) Standard Deviation 12.043	9.123 milliliter (ml) Standard Deviation 12.779
Change From Baseline in Stroke Volume (SV) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 15 hour (n=2,1,0)	-5.022 milliliter (ml) Standard Deviation 1.839	-0.955 milliliter (ml) Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	NA milliliter (ml) Standard Deviation NA No participant was analyzed for this time point

SECONDARY outcome

Timeframe: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour

The SVI was a calculated hemodynamic parameter and the calculation was done on the basis of the measured hemodynamic parameters. Stroke volume is the volume of blood ejected from a ventricle at each beat of the heart, equal to the difference between the end-diastolic volume and the end-systolic volume. The stroke volume index is a method of relating the stroke volume to the size of the person by dividing the stroke volume by the body surface area (BSA).

Outcome measures

SECONDARY outcome

Timeframe: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12 and 24 Hour

The SVR was a calculated hemodynamic parameter and the calculation was done on the basis of the measured hemodynamic parameters. SVR was calculated by dividing (80\*\[MBP-MRAP\]) and CO.

Outcome measures

Outcome measures
Measure	Nesiritide (1+ 0.01) n=19 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) n=18 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) n=16 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.
Change From Baseline in Systemic Vascular Resistance (SVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12 and 24 Hour Baseline (n=19,18,16)	1935.318 dyne*second per centimeter^5 Standard Deviation 687.715	2170.633 dyne*second per centimeter^5 Standard Deviation 896.353	2062.369 dyne*second per centimeter^5 Standard Deviation 894.394
Change From Baseline in Systemic Vascular Resistance (SVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12 and 24 Hour Change at 0.25 hour (n=19,17,16)	-261.453 dyne*second per centimeter^5 Standard Deviation 301.208	-366.981 dyne*second per centimeter^5 Standard Deviation 340.678	-384.379 dyne*second per centimeter^5 Standard Deviation 651.980
Change From Baseline in Systemic Vascular Resistance (SVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12 and 24 Hour Change at 0.5 hour (n=19,18,16)	-229.968 dyne*second per centimeter^5 Standard Deviation 250.083	-453.601 dyne*second per centimeter^5 Standard Deviation 505.637	-686.497 dyne*second per centimeter^5 Standard Deviation 784.338
Change From Baseline in Systemic Vascular Resistance (SVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12 and 24 Hour Change at 1 hour (n=19,18,16)	-265.611 dyne*second per centimeter^5 Standard Deviation 419.843	-456.113 dyne*second per centimeter^5 Standard Deviation 496.625	-611.673 dyne*second per centimeter^5 Standard Deviation 640.704
Change From Baseline in Systemic Vascular Resistance (SVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12 and 24 Hour Change at 1.5 hour (n=19,18,16)	-170.120 dyne*second per centimeter^5 Standard Deviation 551.743	-328.746 dyne*second per centimeter^5 Standard Deviation 299.522	-370.457 dyne*second per centimeter^5 Standard Deviation 458.264
Change From Baseline in Systemic Vascular Resistance (SVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12 and 24 Hour Change at 2 hour (n=19,18,16)	-121.127 dyne*second per centimeter^5 Standard Deviation 652.720	-308.987 dyne*second per centimeter^5 Standard Deviation 378.774	-316.466 dyne*second per centimeter^5 Standard Deviation 580.484
Change From Baseline in Systemic Vascular Resistance (SVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12 and 24 Hour Change at 2.5 hour (n=19,18,16)	49.262 dyne*second per centimeter^5 Standard Deviation 797.660	-292.112 dyne*second per centimeter^5 Standard Deviation 422.397	-220.959 dyne*second per centimeter^5 Standard Deviation 357.619
Change From Baseline in Systemic Vascular Resistance (SVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12 and 24 Hour Change at 3 hour (n=19,18,16)	-81.183 dyne*second per centimeter^5 Standard Deviation 487.205	-297.880 dyne*second per centimeter^5 Standard Deviation 375.627	-219.786 dyne*second per centimeter^5 Standard Deviation 545.724
Change From Baseline in Systemic Vascular Resistance (SVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12 and 24 Hour Change at 4 hour (n=19,17,16)	-18.367 dyne*second per centimeter^5 Standard Deviation 467.058	-339.457 dyne*second per centimeter^5 Standard Deviation 663.324	-184.293 dyne*second per centimeter^5 Standard Deviation 396.692
Change From Baseline in Systemic Vascular Resistance (SVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12 and 24 Hour Change at 5 hour (n=18,17,16)	40.462 dyne*second per centimeter^5 Standard Deviation 592.227	-254.269 dyne*second per centimeter^5 Standard Deviation 425.412	-211.770 dyne*second per centimeter^5 Standard Deviation 375.316
Change From Baseline in Systemic Vascular Resistance (SVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12 and 24 Hour Change at 6 hour (n=18,17,16)	0.026 dyne*second per centimeter^5 Standard Deviation 562.942	-68.635 dyne*second per centimeter^5 Standard Deviation 508.949	-189.116 dyne*second per centimeter^5 Standard Deviation 493.764
Change From Baseline in Systemic Vascular Resistance (SVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12 and 24 Hour Change at 12 hour (n=16,17,16)	157.757 dyne*second per centimeter^5 Standard Deviation 743.728	-26.925 dyne*second per centimeter^5 Standard Deviation 513.032	-327.763 dyne*second per centimeter^5 Standard Deviation 648.264
Change From Baseline in Systemic Vascular Resistance (SVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12 and 24 Hour Change at 24 hour (n=14,17,14)	-88.612 dyne*second per centimeter^5 Standard Deviation 390.796	68.641 dyne*second per centimeter^5 Standard Deviation 921.094	-56.456 dyne*second per centimeter^5 Standard Deviation 477.960

SECONDARY outcome

Timeframe: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour

The PVR (force that opposes the flow of blood through a vascular bed) was a calculated hemodynamic parameter and the calculation was done on the basis of the measured hemodynamic parameters. PVR was calculated by dividing (80\*\[MPAP-PCWP\]) and CO.

Outcome measures

SECONDARY outcome

Timeframe: Baseline, 1 h and 24 h

Assessment of Dyspnea (difficult or labored breathing) was done using Borg scale. It is a 10-point scale where following scores stands for severity of dyspnea: 0=no breathlessness at all; 0.5=very very slight (just noticeable); 1=very slight; 2=slight; 3=moderate; 4=somewhat severe; 5=severe; 7=very severe breathlessness; 9=very very severe (almost maximum) and 10=maximum.

Outcome measures

Outcome measures
Measure	Nesiritide (1+ 0.01) n=17 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) n=20 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) n=17 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 5; at 1 hour:Score 3	0 Participants	0 Participants	1 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 0; at 1 hour:Score 0	1 Participants	2 Participants	4 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 0.5; at 1 hour:Score 1	0 Participants	1 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 1; at 1 hour:Score 0	1 Participants	1 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 1; at 1 hour:Score 1	0 Participants	1 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 8; at 24 hour:Score 1	2 Participants	0 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 1; at 1 hour:Score 2	0 Participants	2 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 2; at 1 hour:Score 0	0 Participants	1 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 2; at 1 hour:Score 0.5	0 Participants	1 Participants	1 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 2; at 1 hour:Score 1	1 Participants	1 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 2; at 1 hour:Score 2	2 Participants	0 Participants	2 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 3; at 1 hour:Score 1	0 Participants	1 Participants	1 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 3; at 1 hour:Score 2	2 Participants	2 Participants	3 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 3; at 1 hour:Score 3	1 Participants	0 Participants	2 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 4; at 1 hour:Score 3	1 Participants	1 Participants	1 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 4; at 1 hour:Score 4	1 Participants	1 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 5; at 1 hour:Score 4	0 Participants	1 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 5; at 1 hour:Score 5	0 Participants	1 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 6; at 1 hour:Score 1	0 Participants	1 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 6; at 1 hour:Score 3	0 Participants	0 Participants	1 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 7; at 1 hour:Score 0	0 Participants	0 Participants	1 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 7; at 1 hour:Score 2	1 Participants	0 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 7; at 1 hour:Score 3	1 Participants	1 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 7; at 1 hour:Score 7	1 Participants	0 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 8; at 1 hour:Score 3	2 Participants	0 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 9; at 1 hour:Score 3	1 Participants	0 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 9; at 1 hour:Score 4	1 Participants	0 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 10; at 1 hour:Score 4	0 Participants	1 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 0; at 24 hour:Score 0	1 Participants	2 Participants	2 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 0; at 24 hour:Score 1	0 Participants	0 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 0.5; at 24 hour:Score 1	0 Participants	1 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 1; at 24 hour:Score 0	1 Participants	1 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 1; at 24 hour:Score 1	0 Participants	3 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 2; at 24 hour:Score 0	0 Participants	1 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 2; at 24 hour:Score 0.5	1 Participants	0 Participants	1 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 2; at 24 hour:Score 1	0 Participants	1 Participants	1 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 2; at 24 hour:Score 2	1 Participants	1 Participants	1 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 3; at 24 hour:Score 0	1 Participants	0 Participants	3 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 3; at 24 hour:Score 0.5	1 Participants	0 Participants	2 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 3; at 24 hour:Score 1	2 Participants	1 Participants	1 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 3; at 24 hour:Score 2	0 Participants	1 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 4; at 24 hour:Score 0	1 Participants	0 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 4; at 24 hour:Score 0.5	0 Participants	1 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 4; at 24 hour:Score 1	0 Participants	1 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 4; at 24 hour:Score 3	0 Participants	0 Participants	1 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 5; at 24 hour:Score 0	0 Participants	1 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 5; at 24 hour:Score 1	0 Participants	0 Participants	1 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 5; at 24 hour:Score 2	0 Participants	1 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 6; at 24 hour:Score 0	0 Participants	1 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 6; at 24 hour:Score 3	0 Participants	0 Participants	1 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 7; at 24 hour:Score 0	0 Participants	1 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 7; at 24 hour:Score 1	1 Participants	0 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 7; at 24 hour:Score 3	1 Participants	0 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score Baseline:Score 7; at 24 hour:Score 4	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 3, 6 and 24 hour

Assessment of Dyspnea was done using Likert scale. It is a 7-point scale where following scores stands for severity of dyspnea: 1=markedly better; 2=moderately better; 3=minimally better; 4=no change; 5=minimally worse; 6=moderately worse and 7= markedly worse

Outcome measures

Outcome measures
Measure	Nesiritide (1+ 0.01) n=13 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) n=15 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) n=17 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.
Number of Participants With Dyspnea Symptoms Assessed by Likert Scale Score At 3 hour: Score 1	5 Participants	4 Participants	6 Participants
Number of Participants With Dyspnea Symptoms Assessed by Likert Scale Score At 3 hour: Score 2	2 Participants	4 Participants	2 Participants
Number of Participants With Dyspnea Symptoms Assessed by Likert Scale Score At 3 hour: Score 3	3 Participants	3 Participants	3 Participants
Number of Participants With Dyspnea Symptoms Assessed by Likert Scale Score At 3 hour: Score 4	3 Participants	4 Participants	5 Participants
Number of Participants With Dyspnea Symptoms Assessed by Likert Scale Score At 3 hour: Score 5	0 Participants	0 Participants	1 Participants
Number of Participants With Dyspnea Symptoms Assessed by Likert Scale Score At 6 hour: Score 1	6 Participants	6 Participants	4 Participants
Number of Participants With Dyspnea Symptoms Assessed by Likert Scale Score At 6 hour: Score 2	3 Participants	2 Participants	5 Participants
Number of Participants With Dyspnea Symptoms Assessed by Likert Scale Score At 6 hour: Score 3	1 Participants	4 Participants	5 Participants
Number of Participants With Dyspnea Symptoms Assessed by Likert Scale Score At 6 hour: Score 4	2 Participants	2 Participants	3 Participants
Number of Participants With Dyspnea Symptoms Assessed by Likert Scale Score At 24 hour: Score 1	4 Participants	7 Participants	8 Participants
Number of Participants With Dyspnea Symptoms Assessed by Likert Scale Score At 24 hour: Score 2	3 Participants	4 Participants	0 Participants
Number of Participants With Dyspnea Symptoms Assessed by Likert Scale Score At 24 hour: Score 3	1 Participants	1 Participants	4 Participants
Number of Participants With Dyspnea Symptoms Assessed by Likert Scale Score At 24 hour: Score 4	2 Participants	2 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline, 1 and 24 hour

Assessment of dyspnea was done by measuring percentage of participants showing presence or absence of orthopnea (it is the sensation of breathlessness in the recumbent position, relieved by sitting or standing) symptoms

Outcome measures

Outcome measures
Measure	Nesiritide (1+ 0.01) n=18 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) n=20 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) n=17 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.
Number of Participants With Orthopnea Baseline: 'Yes'; at 1 hour 'Yes'	6 Participants	4 Participants	4 Participants
Number of Participants With Orthopnea Baseline: 'Yes'; at 1 hour 'No'	7 Participants	7 Participants	1 Participants
Number of Participants With Orthopnea Baseline: 'No'; at 1 hour 'No'	5 Participants	9 Participants	12 Participants
Number of Participants With Orthopnea Baseline: 'Yes'; at 24 hour 'Yes'	1 Participants	2 Participants	1 Participants
Number of Participants With Orthopnea Baseline: 'Yes'; at 24 hour 'No'	7 Participants	8 Participants	4 Participants
Number of Participants With Orthopnea Baseline: 'No'; at 24 hour 'No'	6 Participants	9 Participants	10 Participants

SECONDARY outcome

Timeframe: Baseline,1 and 24 hour

Population: The PPS were the residual participants having a significant protocol deviation influencing the efficacy assessment, obtained by subtracting from the FAS population. Here, N=the participants evaluated for this measure and n=the participants evaluated for this measure at a particular time point.

Assessment of dyspnea was done by measuring number of participants showing presence or absence of oxygen therapy.

Outcome measures

Outcome measures
Measure	Nesiritide (1+ 0.01) n=18 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) n=20 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) n=17 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.
Number of Participants With Oxygen Therapy Baseline: 'Yes';at 1 hour 'Yes'(n=18,20,17	16 Participants	20 Participants	17 Participants
Number of Participants With Oxygen Therapy Baseline: 'No';at 1 hour 'No'(n=18,20,17)	2 Participants	0 Participants	0 Participants
Number of Participants With Oxygen Therapy Baseline: 'Yes';at 24 hour 'Yes'(n=14,19,15)	12 Participants	19 Participants	15 Participants
Number of Participants With Oxygen Therapy Baseline:'No';at 24 hour 'No'(n=14,19,15)	2 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, 1, 2, 3, 6, 9, 12, 15 and 24 hour

Population: The PPS were the residual participants having a significant protocol deviation influencing the efficacy assessment, obtained by subtracting from the FAS population. Here,n=the participants evaluated for this measure at a particular time point.

Assessment of dyspnea was done by measuring SpO2 via pulse oximetry, by making the participant lye quietly in the post anesthesia care unit (PACU) and breathing room air (RA)

Outcome measures

Outcome measures
Measure	Nesiritide (1+ 0.01) n=19 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) n=20 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) n=17 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.
Assessment of Dyspnea Using Percutaneous Arterial Oxygen Saturation (SpO2) Baseline (n=19,20,17)	96.5 Percentage of SpO2 Standard Deviation 2.9	96.4 Percentage of SpO2 Standard Deviation 2.3	96.9 Percentage of SpO2 Standard Deviation 2.0
Assessment of Dyspnea Using Percutaneous Arterial Oxygen Saturation (SpO2) At 1 hour (n=18,20,17)	96.6 Percentage of SpO2 Standard Deviation 2.2	96.6 Percentage of SpO2 Standard Deviation 2.2	96.4 Percentage of SpO2 Standard Deviation 5.2
Assessment of Dyspnea Using Percutaneous Arterial Oxygen Saturation (SpO2) At 2 hour (n=19,20,17)	96.8 Percentage of SpO2 Standard Deviation 2.3	96.8 Percentage of SpO2 Standard Deviation 2.4	97.7 Percentage of SpO2 Standard Deviation 1.4
Assessment of Dyspnea Using Percutaneous Arterial Oxygen Saturation (SpO2) At 3 hour (n=19,20,17)	96.7 Percentage of SpO2 Standard Deviation 2.7	96.9 Percentage of SpO2 Standard Deviation 2.6	98.4 Percentage of SpO2 Standard Deviation 0.9
Assessment of Dyspnea Using Percutaneous Arterial Oxygen Saturation (SpO2) At 6 hour (n=13,15,17)	97.6 Percentage of SpO2 Standard Deviation 1.8	97.3 Percentage of SpO2 Standard Deviation 1.9	97.5 Percentage of SpO2 Standard Deviation 1.5
Assessment of Dyspnea Using Percutaneous Arterial Oxygen Saturation (SpO2) At 9 hour (n=0,1,0)	NA Percentage of SpO2 Standard Deviation NA No participant was analyzed for this time point	100.0 Percentage of SpO2 Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	NA Percentage of SpO2 Standard Deviation NA No participant was analyzed for this time point
Assessment of Dyspnea Using Percutaneous Arterial Oxygen Saturation (SpO2) At 15 hour (n=2,1,0)	94.5 Percentage of SpO2 Standard Deviation 3.5	99.0 Percentage of SpO2 Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	NA Percentage of SpO2 Standard Deviation NA No participant was analyzed for this time point
Assessment of Dyspnea Using Percutaneous Arterial Oxygen Saturation (SpO2) At 24 hour (n=14,19,15)	97.1 Percentage of SpO2 Standard Deviation 1.8	97.1 Percentage of SpO2 Standard Deviation 1.8	98.1 Percentage of SpO2 Standard Deviation 1.8

SECONDARY outcome

Timeframe: Baseline, 1, 2, 3, 6, 9, 15 and 24 hour

Population: The PPS included participants who met the eligibility criteria, received at least 1 dose of study medication and had one efficacy assessment after randomization except those who had significant protocol deviations. Here, n=the participants evaluated for this measure at a particular time point.

Assessment of dyspnea was done by measuring respiratory rate which is the number of times an organism breathes with the lungs (respiration) per unit time, usually per minute

Outcome measures

Outcome measures
Measure	Nesiritide (1+ 0.01) n=19 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) n=20 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) n=17 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.
Assessment of Dyspnea Using Respiratory Rate Baseline (n= 19,20,17)	24.7 Breaths Per Minute (BrPM) Standard Deviation 7.8	25.6 Breaths Per Minute (BrPM) Standard Deviation 6.5	23.8 Breaths Per Minute (BrPM) Standard Deviation 7.8
Assessment of Dyspnea Using Respiratory Rate At 1 hour (n= 18,20,17)	24.0 Breaths Per Minute (BrPM) Standard Deviation 8.3	23.0 Breaths Per Minute (BrPM) Standard Deviation 3.9	22.6 Breaths Per Minute (BrPM) Standard Deviation 6.5
Assessment of Dyspnea Using Respiratory Rate At 2 hour (n= 19,20,17)	23.2 Breaths Per Minute (BrPM) Standard Deviation 7.7	22.1 Breaths Per Minute (BrPM) Standard Deviation 4.1	21.2 Breaths Per Minute (BrPM) Standard Deviation 6.2
Assessment of Dyspnea Using Respiratory Rate At 3 hour (n= 19,20,17)	22.7 Breaths Per Minute (BrPM) Standard Deviation 7.1	22.9 Breaths Per Minute (BrPM) Standard Deviation 5.1	20.4 Breaths Per Minute (BrPM) Standard Deviation 6.7
Assessment of Dyspnea Using Respiratory Rate At 6 hour (n= 13,15,17)	21.2 Breaths Per Minute (BrPM) Standard Deviation 3.7	21.8 Breaths Per Minute (BrPM) Standard Deviation 4.9	20.5 Breaths Per Minute (BrPM) Standard Deviation 4.9
Assessment of Dyspnea Using Respiratory Rate At 9 hour (n= 0,1,0)	NA Breaths Per Minute (BrPM) Standard Deviation NA No participant was analyzed for this time point	22.0 Breaths Per Minute (BrPM) Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	NA Breaths Per Minute (BrPM) Standard Deviation NA No participant was analyzed for this time point
Assessment of Dyspnea Using Respiratory Rate At 15 hour (n=2,1,0)	22.0 Breaths Per Minute (BrPM) Standard Deviation 7.1	33.0 Breaths Per Minute (BrPM) Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	NA Breaths Per Minute (BrPM) Standard Deviation NA No participant was analyzed for this time point
Assessment of Dyspnea Using Respiratory Rate At 24 hour (n= 14,18,17)	19.4 Breaths Per Minute (BrPM) Standard Deviation 3.9	20.8 Breaths Per Minute (BrPM) Standard Deviation 5.0	21.4 Breaths Per Minute (BrPM) Standard Deviation 4.3

SECONDARY outcome

Timeframe: Baseline, 3 and 24 hour

Population: The PPS included participants who met the eligibility criteria, received at least 1 dose of study medication and had one efficacy assessment after randomization except those who had significant protocol deviations. Here, n=the participants evaluated for this measure at a particular time point.

The urinary volume was measured because nesiritide has a diuretic effect. Measurement of hour urine was done in the observation period and treatment period. 1-hour urine before treatment initiation was measured in the observation period. In the treatment period, 1-hour urine for period 1 and 3-hour urine for period 2 was measured. Urinary volume was recorded for participants without urethral catheterization having spontaneous micturition when needed.

Outcome measures

Outcome measures
Measure	Nesiritide (1+ 0.01) n=19 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) n=20 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) n=17 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.
Urinary Volume Baseline (n=15,19,15)	83.9 Millliter Standard Deviation 69.5	67.0 Millliter Standard Deviation 36.1	79.7 Millliter Standard Deviation 110.6
Urinary Volume At 3 hour (n=19,20,17)	539.9 Millliter Standard Deviation 333.5	423.6 Millliter Standard Deviation 289.4	545.1 Millliter Standard Deviation 643.6
Urinary Volume At 24 hour (n=19,20,17)	1976.3 Millliter Standard Deviation 1296.0	2296.9 Millliter Standard Deviation 1278.7	2233.6 Millliter Standard Deviation 1569.6

Adverse Events

Nesiritide (1+ 0.01)

Serious events: 3 serious events

Other events: 18 other events

Deaths: 0 deaths

Nesiritide (2+0.005)

Serious events: 3 serious events

Other events: 16 other events

Deaths: 0 deaths

Nesiritide (2+0.01)

Serious events: 4 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Nesiritide (1+ 0.01) n=21 participants at risk Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) n=20 participants at risk Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) n=19 participants at risk Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.
Cardiac disorders Cardiac failure	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	10.5% 2/19 • Baseline up to 30 days
Renal and urinary disorders Renal failure acute	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Infections and infestations Infection	0.00% 0/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Vascular disorders Cerebral infarction	0.00% 0/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Vascular disorders Cerebral artery embolism	0.00% 0/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
Infections and infestations Sepsis	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Hepatobiliary disorders Bile duct stone	0.00% 0/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days

Other adverse events

Other adverse events
Measure	Nesiritide (1+ 0.01) n=21 participants at risk Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) n=20 participants at risk Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) n=19 participants at risk Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.
Infections and infestations Infection	0.00% 0/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	10.5% 2/19 • Baseline up to 30 days
Infections and infestations Cystitis	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Infections and infestations Endocarditis	0.00% 0/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Infections and infestations Gastroenteritis	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Infections and infestations Nasopharyngitis	0.00% 0/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
Infections and infestations Pharyngitis	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Infections and infestations Urinary tract infection	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Infections and infestations Enteritis infectious	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Blood and lymphatic system disorders Anaemia	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Blood and lymphatic system disorders Disseminated intravascular coagulation	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Metabolism and nutrition disorders Dehydration	0.00% 0/21 • Baseline up to 30 days	15.0% 3/20 • Baseline up to 30 days	10.5% 2/19 • Baseline up to 30 days
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	10.5% 2/19 • Baseline up to 30 days
Metabolism and nutrition disorders Hypoproteinaemia	0.00% 0/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
Metabolism and nutrition disorders Hyperuricaemia	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Metabolism and nutrition disorders Hyperamylasaemia	0.00% 0/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Psychiatric disorders Insomnia	14.3% 3/21 • Baseline up to 30 days	10.0% 2/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
Psychiatric disorders Mental disorder due to a general medical condition	4.8% 1/21 • Baseline up to 30 days	10.0% 2/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
Psychiatric disorders Delirium	4.8% 1/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Psychiatric disorders Restlessness	4.8% 1/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Psychiatric disorders Anxiety disorder	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Nervous system disorders Cholinergic syndrome	0.00% 0/21 • Baseline up to 30 days	10.0% 2/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Cardiac disorders Cardiac failure	9.5% 2/21 • Baseline up to 30 days	15.0% 3/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Cardiac disorders Ventricular extrasystoles	0.00% 0/21 • Baseline up to 30 days	10.0% 2/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Cardiac disorders Ventricular tachycardia	0.00% 0/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	10.5% 2/19 • Baseline up to 30 days
Cardiac disorders Cardiac failure chronic	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Cardiac disorders Supraventricular extrasystoles	0.00% 0/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Vascular disorders Hypotension	14.3% 3/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	10.5% 2/19 • Baseline up to 30 days
Vascular disorders Peripheral circulatory failure	0.00% 0/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Gastrointestinal disorders Nausea	9.5% 2/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Gastrointestinal disorders Constipation	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
Gastrointestinal disorders Diarrhoea	4.8% 1/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Gastrointestinal disorders Vomiting	0.00% 0/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
Gastrointestinal disorders Glossoptosis	0.00% 0/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
Hepatobiliary disorders Hepatic function abnormal	4.8% 1/21 • Baseline up to 30 days	15.0% 3/20 • Baseline up to 30 days	10.5% 2/19 • Baseline up to 30 days
Hepatobiliary disorders Hepatic congestion	0.00% 0/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Skin and subcutaneous tissue disorders Eczema	0.00% 0/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
Skin and subcutaneous tissue disorders Dermatitis atopic	0.00% 0/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Skin and subcutaneous tissue disorders Drug eruption	0.00% 0/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Skin and subcutaneous tissue disorders Skin erosion	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Musculoskeletal and connective tissue disorders Back pain	9.5% 2/21 • Baseline up to 30 days	10.0% 2/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Musculoskeletal and connective tissue disorders Arthralgia	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Musculoskeletal and connective tissue disorders Neck pain	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Musculoskeletal and connective tissue disorders Osteoporotic fracture	0.00% 0/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.00% 0/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Renal and urinary disorders Renal impairment	0.00% 0/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
Renal and urinary disorders Haematuria	0.00% 0/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
Renal and urinary disorders Polyuria	0.00% 0/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
Renal and urinary disorders Proteinuria	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Renal and urinary disorders Renal failure acute	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Renal and urinary disorders Urinary retention	0.00% 0/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
General disorders Catheter site haemorrhage	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
General disorders Chest discomfort	0.00% 0/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
General disorders Pain	0.00% 0/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
General disorders Pyrexia	0.00% 0/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
General disorders Catheter site pain	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
General disorders Infusion site phlebitis	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
General disorders Vessel puncture site haemorrhage	0.00% 0/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
General disorders Vessel puncture site haematoma	0.00% 0/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
Investigations Platelet count decreased	9.5% 2/21 • Baseline up to 30 days	10.0% 2/20 • Baseline up to 30 days	10.5% 2/19 • Baseline up to 30 days
Investigations Blood urine present	9.5% 2/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	10.5% 2/19 • Baseline up to 30 days
Investigations Blood urea increased	4.8% 1/21 • Baseline up to 30 days	15.0% 3/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Investigations Blood potassium increased	0.00% 0/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
Investigations Blood uric acid increased	0.00% 0/21 • Baseline up to 30 days	10.0% 2/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Investigations Eosinophil count increased	0.00% 0/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
Investigations Basophil count increased	0.00% 0/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
Investigations Blood albumin decreased	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Investigations Blood bilirubin increased	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Investigations Blood creatine phosphokinase increased	0.00% 0/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Investigations Blood creatinine increased	0.00% 0/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
Investigations Blood potassium decreased	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Investigations Blood triglycerides increased	0.00% 0/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Investigations Laboratory test abnormal	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Investigations Protein total decreased	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Investigations Pulmonary arterial wedge pressure increased	0.00% 0/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Investigations Red blood cell count decreased	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Investigations Platelet count increased	0.00% 0/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	5.3% 1/19 • Baseline up to 30 days
Investigations Protein urine present	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Investigations Blood alkaline phosphatase increased	4.8% 1/21 • Baseline up to 30 days	0.00% 0/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days
Injury, poisoning and procedural complications Fall	14.3% 3/21 • Baseline up to 30 days	5.0% 1/20 • Baseline up to 30 days	0.00% 0/19 • Baseline up to 30 days

Additional Information

Manager

Clinical Science Initiative Dept. Janssen Pharmaceutical K.K./ Tokyo Japan

Phone: +81.3.4411.5653

Results disclosure agreements

Principal investigator is a sponsor employee The disclosure restriction on PI is that the Sponsor can review results communications prior to public release and can embargo communications regarding results for a period as the Sponsor requires.
Publication restrictions are in place

Restriction type: OTHER

Measure	Nesiritide (1+ 0.01) n=19 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) n=20 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) n=17 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.
Change From Baseline in Pulmonary Arterial Systolic Pressure (PASP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Baseline (n=19,20,17)	55.9 Millimeters of mercury Standard Deviation 16.5	51.3 Millimeters of mercury Standard Deviation 11.1	59.8 Millimeters of mercury Standard Deviation 12.0
Change From Baseline in Pulmonary Arterial Systolic Pressure (PASP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 0.25 hour (n=19,19,17)	-3.6 Millimeters of mercury Standard Deviation 6.2	-8.2 Millimeters of mercury Standard Deviation 7.9	-4.2 Millimeters of mercury Standard Deviation 5.2
Change From Baseline in Pulmonary Arterial Systolic Pressure (PASP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 0.5 hour (n=19,20,17)	-5.3 Millimeters of mercury Standard Deviation 7.6	-8.7 Millimeters of mercury Standard Deviation 9.5	-5.5 Millimeters of mercury Standard Deviation 4.8
Change From Baseline in Pulmonary Arterial Systolic Pressure (PASP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 1 hour (n=19,20,17)	-7.0 Millimeters of mercury Standard Deviation 8.8	-8.7 Millimeters of mercury Standard Deviation 9.5	-7.4 Millimeters of mercury Standard Deviation 5.7
Change From Baseline in Pulmonary Arterial Systolic Pressure (PASP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 1.5 hour (n=19,20,17)	-6.2 Millimeters of mercury Standard Deviation 9.1	-7.6 Millimeters of mercury Standard Deviation 8.0	-8.8 Millimeters of mercury Standard Deviation 6.6
Change From Baseline in Pulmonary Arterial Systolic Pressure (PASP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 2 hour (n=19,20,17)	-7.2 Millimeters of mercury Standard Deviation 8.6	-6.8 Millimeters of mercury Standard Deviation 9.1	-7.0 Millimeters of mercury Standard Deviation 6.3
Change From Baseline in Pulmonary Arterial Systolic Pressure (PASP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 2.5 hour (n=19,20,17)	-7.0 Millimeters of mercury Standard Deviation 9.8	-5.9 Millimeters of mercury Standard Deviation 7.4	-6.6 Millimeters of mercury Standard Deviation 6.9
Change From Baseline in Pulmonary Arterial Systolic Pressure (PASP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 3 hour (n=19,20,17)	-9.4 Millimeters of mercury Standard Deviation 10.5	-6.1 Millimeters of mercury Standard Deviation 8.9	-6.4 Millimeters of mercury Standard Deviation 7.8
Change From Baseline in Pulmonary Arterial Systolic Pressure (PASP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 4 hour (n=19,19,17)	-10.2 Millimeters of mercury Standard Deviation 12.2	-5.7 Millimeters of mercury Standard Deviation 9.2	-7.5 Millimeters of mercury Standard Deviation 6.9
Change From Baseline in Pulmonary Arterial Systolic Pressure (PASP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 5 hour (n=18,19,17)	-10.0 Millimeters of mercury Standard Deviation 12.6	-6.8 Millimeters of mercury Standard Deviation 9.5	-8.2 Millimeters of mercury Standard Deviation 6.0
Change From Baseline in Pulmonary Arterial Systolic Pressure (PASP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 6 hour (n=18,19,17)	-9.9 Millimeters of mercury Standard Deviation 12.1	-6.1 Millimeters of mercury Standard Deviation 9.7	-10.1 Millimeters of mercury Standard Deviation 7.7
Change From Baseline in Pulmonary Arterial Systolic Pressure (PASP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 9 hour (n=0,1,0)	NA Millimeters of mercury Standard Deviation NA No participant was analyzed for this time point	13.0 Millimeters of mercury Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	NA Millimeters of mercury Standard Deviation NA No participant was analyzed for this time point
Change From Baseline in Pulmonary Arterial Systolic Pressure (PASP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 12 hour (n=17,19,17)	-11.3 Millimeters of mercury Standard Deviation 12.9	-9.1 Millimeters of mercury Standard Deviation 10.4	-12.7 Millimeters of mercury Standard Deviation 7.7
Change From Baseline in Pulmonary Arterial Systolic Pressure (PASP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 15 hour (n=2,1,0)	6.0 Millimeters of mercury Standard Deviation 4.9	6.0 Millimeters of mercury Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	NA Millimeters of mercury Standard Deviation NA No participant was analyzed for this time point
Change From Baseline in Pulmonary Arterial Systolic Pressure (PASP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 24 hour (n=14,19,15)	-9.3 Millimeters of mercury Standard Deviation 10.5	-10.4 Millimeters of mercury Standard Deviation 11.9	-12.2 Millimeters of mercury Standard Deviation 7.6

Measure	Nesiritide (1+ 0.01) n=19 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) n=20 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) n=17 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.
Change From Baseline in Pulmonary Arterial Diastolic Pressure (PADP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 12 hour (n=17,19,17)	-6.8 Millimeters of mercury Standard Deviation 8.3	-5.6 Millimeters of mercury Standard Deviation 5.2	-8.9 Millimeters of mercury Standard Deviation 7.6
Change From Baseline in Pulmonary Arterial Diastolic Pressure (PADP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 15 hour (n=2,1,0)	3.5 Millimeters of mercury Standard Deviation 4.9	3.5 Millimeters of mercury Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	NA Millimeters of mercury Standard Deviation NA No participant was analyzed for this time point
Change From Baseline in Pulmonary Arterial Diastolic Pressure (PADP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Baseline (n=19,20,17)	26.5 Millimeters of mercury Standard Deviation 8.4	24.2 Millimeters of mercury Standard Deviation 7.4	30.1 Millimeters of mercury Standard Deviation 8.0
Change From Baseline in Pulmonary Arterial Diastolic Pressure (PADP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 0.25 hour (n=19,19,17)	-1.6 Millimeters of mercury Standard Deviation 3.1	-6.1 Millimeters of mercury Standard Deviation 4.6	-4.6 Millimeters of mercury Standard Deviation 3.3
Change From Baseline in Pulmonary Arterial Diastolic Pressure (PADP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 0.5 hour (n=19,20,17)	-2.8 Millimeters of mercury Standard Deviation 4.0	-6.9 Millimeters of mercury Standard Deviation 5.6	-6.6 Millimeters of mercury Standard Deviation 4.3
Change From Baseline in Pulmonary Arterial Diastolic Pressure (PADP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 1 hour (n=19,20,17)	-4.0 Millimeters of mercury Standard Deviation 6.0	-5.7 Millimeters of mercury Standard Deviation 6.1	-7.0 Millimeters of mercury Standard Deviation 4.4
Change From Baseline in Pulmonary Arterial Diastolic Pressure (PADP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 1.5 hour (n=19,20,17)	-3.2 Millimeters of mercury Standard Deviation 6.5	-5.6 Millimeters of mercury Standard Deviation 5.5	-6.9 Millimeters of mercury Standard Deviation 4.3
Change From Baseline in Pulmonary Arterial Diastolic Pressure (PADP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 2 hour (n=19,20,17)	-4.6 Millimeters of mercury Standard Deviation 6.4	-5.4 Millimeters of mercury Standard Deviation 5.3	-5.6 Millimeters of mercury Standard Deviation 5.3
Change From Baseline in Pulmonary Arterial Diastolic Pressure (PADP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 2.5 (n=19,20,17)	-3.5 Millimeters of mercury Standard Deviation 6.9	-3.6 Millimeters of mercury Standard Deviation 4.8	-6.2 Millimeters of mercury Standard Deviation 5.9
Change From Baseline in Pulmonary Arterial Diastolic Pressure (PADP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 3 hour (n=19,20,17)	-4.7 Millimeters of mercury Standard Deviation 6.7	-3.6 Millimeters of mercury Standard Deviation 5.3	-5.9 Millimeters of mercury Standard Deviation 6.0
Change From Baseline in Pulmonary Arterial Diastolic Pressure (PADP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 4 hour (n=19,19,17)	-6.7 Millimeters of mercury Standard Deviation 7.1	-4.4 Millimeters of mercury Standard Deviation 5.6	-6.5 Millimeters of mercury Standard Deviation 5.6
Change From Baseline in Pulmonary Arterial Diastolic Pressure (PADP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 5 hour (n=18,19,17)	-6.3 Millimeters of mercury Standard Deviation 7.5	-4.5 Millimeters of mercury Standard Deviation 5.4	-6.5 Millimeters of mercury Standard Deviation 5.2
Change From Baseline in Pulmonary Arterial Diastolic Pressure (PADP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 6 hour (n=18,19,17)	-6.7 Millimeters of mercury Standard Deviation 6.9	-4.1 Millimeters of mercury Standard Deviation 5.6	-8.0 Millimeters of mercury Standard Deviation 5.8
Change From Baseline in Pulmonary Arterial Diastolic Pressure (PADP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 9 hour (n=0,1,0)	NA Millimeters of mercury Standard Deviation NA No participant was analyzed for this time point	14.0 Millimeters of mercury Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	NA Millimeters of mercury Standard Deviation NA No participant was analyzed for this time point
Change From Baseline in Pulmonary Arterial Diastolic Pressure (PADP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 24 hour (n=14,19,15)	-5.7 Millimeters of mercury Standard Deviation 5.9	-6.0 Millimeters of mercury Standard Deviation 6.4	-8.0 Millimeters of mercury Standard Deviation 6.4

Measure	Nesiritide (1+ 0.01) n=19 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) n=20 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) n=17 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.
Change From Baseline in Mean Pulmonary Arterial Pressure (MPAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Baseline (n=19,20,17)	38.2 Millimeters of mercury Standard Deviation 10.8	34.5 Millimeters of mercury Standard Deviation 8.5	42.6 Millimeters of mercury Standard Deviation 7.8
Change From Baseline in Mean Pulmonary Arterial Pressure (MPAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 0.25 hour (n=19,19,17)	-2.3 Millimeters of mercury Standard Deviation 3.8	-7.0 Millimeters of mercury Standard Deviation 5.5	-4.9 Millimeters of mercury Standard Deviation 4.6
Change From Baseline in Mean Pulmonary Arterial Pressure (MPAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 0.5 hour (n=19,20,17)	-3.2 Millimeters of mercury Standard Deviation 5.0	-7.6 Millimeters of mercury Standard Deviation 7.2	-5.5 Millimeters of mercury Standard Deviation 4.4
Change From Baseline in Mean Pulmonary Arterial Pressure (MPAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 1 hour (n=19,20,17)	-5.0 Millimeters of mercury Standard Deviation 5.9	-6.7 Millimeters of mercury Standard Deviation 7.4	-7.8 Millimeters of mercury Standard Deviation 5.4
Change From Baseline in Mean Pulmonary Arterial Pressure (MPAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 1.5 hour (n=19,20,17)	-4.8 Millimeters of mercury Standard Deviation 7.4	-6.7 Millimeters of mercury Standard Deviation 6.6	-7.8 Millimeters of mercury Standard Deviation 5.8
Change From Baseline in Mean Pulmonary Arterial Pressure (MPAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 2 hour (n=19,20,17)	-5.3 Millimeters of mercury Standard Deviation 7.0	-5.7 Millimeters of mercury Standard Deviation 7.1	-6.4 Millimeters of mercury Standard Deviation 5.8
Change From Baseline in Mean Pulmonary Arterial Pressure (MPAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 2.5 hour (n=19,20,17)	-5.4 Millimeters of mercury Standard Deviation 7.0	-4.9 Millimeters of mercury Standard Deviation 7.8	-6.7 Millimeters of mercury Standard Deviation 6.5
Change From Baseline in Mean Pulmonary Arterial Pressure (MPAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 3 hour (n=19,20,17)	-6.5 Millimeters of mercury Standard Deviation 7.6	-5.6 Millimeters of mercury Standard Deviation 8.5	-5.9 Millimeters of mercury Standard Deviation 6.1
Change From Baseline in Mean Pulmonary Arterial Pressure (MPAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 4 hour (n=19,19,17)	-8.3 Millimeters of mercury Standard Deviation 8.3	-5.0 Millimeters of mercury Standard Deviation 7.1	-7.1 Millimeters of mercury Standard Deviation 6.1
Change From Baseline in Mean Pulmonary Arterial Pressure (MPAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 5 hour (n=18,19,17)	-7.5 Millimeters of mercury Standard Deviation 8.7	-6.3 Millimeters of mercury Standard Deviation 6.8	-7.8 Millimeters of mercury Standard Deviation 4.7
Change From Baseline in Mean Pulmonary Arterial Pressure (MPAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 6 hour (n=18,19,17)	-7.7 Millimeters of mercury Standard Deviation 8.4	-6.0 Millimeters of mercury Standard Deviation 7.2	-9.5 Millimeters of mercury Standard Deviation 7.0
Change From Baseline in Mean Pulmonary Arterial Pressure (MPAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 9 hour (n=0,1,0)	NA Millimeters of mercury Standard Deviation NA No participant was analyzed for this time point	12.5 Millimeters of mercury Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	NA Millimeters of mercury Standard Deviation NA No participant was analyzed for this time point
Change From Baseline in Mean Pulmonary Arterial Pressure (MPAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 12 hour (n=17,19,17)	-8.1 Millimeters of mercury Standard Deviation 10.6	-7.8 Millimeters of mercury Standard Deviation 6.7	-11.3 Millimeters of mercury Standard Deviation 7.0
Change From Baseline in Mean Pulmonary Arterial Pressure (MPAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 15 hour (n=2,1,0)	3.5 Millimeters of mercury Standard Deviation 7.1	4.5 Millimeters of mercury Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	NA Millimeters of mercury Standard Deviation NA No participant was analyzed for this time point
Change From Baseline in Mean Pulmonary Arterial Pressure (MPAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 24 hour (n=14,19,15)	-7.0 Millimeters of mercury Standard Deviation 7.2	-8.6 Millimeters of mercury Standard Deviation 9.0	-11.0 Millimeters of mercury Standard Deviation 6.1

Measure	Nesiritide (1+ 0.01) n=14 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) n=18 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) n=12 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Baseline (n=14,18,14)	27.0 Millimeters of mercury Standard Deviation 6.0	24.3 Millimeters of mercury Standard Deviation 5.1	30.2 Millimeters of mercury Standard Deviation 7.0
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 0.25 hour (n=14,17,13)	-3.5 Millimeters of mercury Standard Deviation 3.7	-5.5 Millimeters of mercury Standard Deviation 3.9	-5.1 Millimeters of mercury Standard Deviation 6.0
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 0.5 hour (n=14,18,13)	-5.1 Millimeters of mercury Standard Deviation 3.4	-7.9 Millimeters of mercury Standard Deviation 5.5	-7.5 Millimeters of mercury Standard Deviation 5.5
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 1 hour (n=14,18,12)	-5.6 Millimeters of mercury Standard Deviation 4.5	-7.6 Millimeters of mercury Standard Deviation 5.3	-8.5 Millimeters of mercury Standard Deviation 5.8
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 1.5 hour (n=14,18,12)	-5.5 Millimeters of mercury Standard Deviation 3.5	-6.5 Millimeters of mercury Standard Deviation 4.7	9.0 Millimeters of mercury Standard Deviation 6.2
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 2 hour (n=14,18,12)	-5.1 Millimeters of mercury Standard Deviation 3.8	-6.3 Millimeters of mercury Standard Deviation 5.1	-7.6 Millimeters of mercury Standard Deviation 6.0
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 2.5 hour (n=14,18,12)	-5.6 Millimeters of mercury Standard Deviation 4.9	-5.0 Millimeters of mercury Standard Deviation 5.7	-7.9 Millimeters of mercury Standard Deviation 6.4
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 3 hour (n=14,18,12)	-6.5 Millimeters of mercury Standard Deviation 4.6	-4.9 Millimeters of mercury Standard Deviation 6.2	-7.9 Millimeters of mercury Standard Deviation 5.5
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 4 hour (n=14,17,12)	-7.9 Millimeters of mercury Standard Deviation 3.8	-4.9 Millimeters of mercury Standard Deviation 6.2	-7.5 Millimeters of mercury Standard Deviation 5.8
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 5 hour (n=12,17,12)	-8.6 Millimeters of mercury Standard Deviation 2.9	-5.8 Millimeters of mercury Standard Deviation 5.8	-8.0 Millimeters of mercury Standard Deviation 5.0
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 6 hour (n=12,17,12)	-9.5 Millimeters of mercury Standard Deviation 3.0	-5.6 Millimeters of mercury Standard Deviation 4.9	-11.2 Millimeters of mercury Standard Deviation 5.9
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 9 hour (n=0,1,0)	NA Millimeters of mercury Standard Deviation NA No participant was analyzed for this time point	12.0 Millimeters of mercury Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	NA Millimeters of mercury Standard Deviation NA No participant was analyzed for this time point
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 12 hour (n=10,17,12)	-9.9 Millimeters of mercury Standard Deviation 3.6	-7.8 Millimeters of mercury Standard Deviation 4.9	-11.8 Millimeters of mercury Standard Deviation 6.5
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 15 hour (n=1,1,0)	-4.5 Millimeters of mercury Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	-1.0 Millimeters of mercury Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	NA Millimeters of mercury Standard Deviation NA No participant was analyzed for this time point
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 24 hour (n=9,17,10)	-9.7 Millimeters of mercury Standard Deviation 6.6	-7.2 Millimeters of mercury Standard Deviation 5.5	-10.5 Millimeters of mercury Standard Deviation 3.9

Measure	Nesiritide (1+ 0.01) n=19 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) n=20 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) n=17 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.
Change From Baseline in Mean Blood Pressure (MBP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 Hour Baseline (n=19,20,17)	109.397 Millimeters of mercury Standard Deviation 15.868	106.169 Millimeters of mercury Standard Deviation 20.438	105.006 Millimeters of mercury Standard Deviation 17.781
Change From Baseline in Mean Blood Pressure (MBP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 Hour Change at 0.25 hour (n=19,19,17)	-6.053 Millimeters of mercury Standard Deviation 6.452	-9.167 Millimeters of mercury Standard Deviation 8.975	-7.098 Millimeters of mercury Standard Deviation 14.093
Change From Baseline in Mean Blood Pressure (MBP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 Hour Change at 0.5 hour (n=19,20,17)	-4.626 Millimeters of mercury Standard Deviation 7.316	-9.930 Millimeters of mercury Standard Deviation 8.124	-9.450 Millimeters of mercury Standard Deviation 10.543
Change From Baseline in Mean Blood Pressure (MBP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 Hour Change at 1 hour (n=19,20,17)	-6.900 Millimeters of mercury Standard Deviation 8.890	-7.863 Millimeters of mercury Standard Deviation 8.599	-7.685 Millimeters of mercury Standard Deviation 12.821
Change From Baseline in Mean Blood Pressure (MBP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 Hour Change at 1.5 hour (n=19,20,17)	-7.412 Millimeters of mercury Standard Deviation 12.835	-10.181 Millimeters of mercury Standard Deviation 9.339	4.969 Millimeters of mercury Standard Deviation 11.997
Change From Baseline in Mean Blood Pressure (MBP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 Hour Change at 2 hour (n=19,20,17)	-10.032 Millimeters of mercury Standard Deviation 11.474	-11.149 Millimeters of mercury Standard Deviation 10.411	-6.669 Millimeters of mercury Standard Deviation 9.468
Change From Baseline in Mean Blood Pressure (MBP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 Hour Change at 2.5 hour (n=19,20,17)	-8.497 Millimeters of mercury Standard Deviation 14.396	-12.516 Millimeters of mercury Standard Deviation 9.011	-6.890 Millimeters of mercury Standard Deviation 10.768
Change From Baseline in Mean Blood Pressure (MBP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 Hour Change at 3 hour (n=19,20,17)	-8.773 Millimeters of mercury Standard Deviation 14.660	-11.666 Millimeters of mercury Standard Deviation 9.572	-9.517 Millimeters of mercury Standard Deviation 11.114
Change From Baseline in Mean Blood Pressure (MBP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 Hour Change at 4 hour (n=19,20,17)	-10.310 Millimeters of mercury Standard Deviation 12.873	-10.858 Millimeters of mercury Standard Deviation 10.196	-5.681 Millimeters of mercury Standard Deviation 11.438
Change From Baseline in Mean Blood Pressure (MBP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 Hour Change at 5 hour (n=18,20,17)	-12.541 Millimeters of mercury Standard Deviation 11.645	-9.301 Millimeters of mercury Standard Deviation 10.935	-8.254 Millimeters of mercury Standard Deviation 11.070
Change From Baseline in Mean Blood Pressure (MBP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 Hour Change at 6 hour (n=19,20,17)	-15.167 Millimeters of mercury Standard Deviation 17.875	-12.241 Millimeters of mercury Standard Deviation 16.070	-9.281 Millimeters of mercury Standard Deviation 12.960
Change From Baseline in Mean Blood Pressure (MBP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 Hour Change at 9 hour (n=19,20,17)	-17.689 Millimeters of mercury Standard Deviation 17.866	-9.287 Millimeters of mercury Standard Deviation 17.532	-14.619 Millimeters of mercury Standard Deviation 14.311
Change From Baseline in Mean Blood Pressure (MBP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 Hour Change at 12 hour (n=19,20,17)	-16.107 Millimeters of mercury Standard Deviation 19.174	-13.113 Millimeters of mercury Standard Deviation 13.733	-16.103 Millimeters of mercury Standard Deviation 15.392
Change From Baseline in Mean Blood Pressure (MBP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 Hour Change at 15 hour (n=19,20,17)	-16.050 Millimeters of mercury Standard Deviation 18.244	-11.584 Millimeters of mercury Standard Deviation 15.233	-15.590 Millimeters of mercury Standard Deviation 13.885
Change From Baseline in Mean Blood Pressure (MBP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 Hour Change at 18 hour (n=19,20,17)	-16.040 Millimeters of mercury Standard Deviation 21.176	-16.331 Millimeters of mercury Standard Deviation 16.193	-15.962 Millimeters of mercury Standard Deviation 16.456
Change From Baseline in Mean Blood Pressure (MBP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 Hour Change at 21 hour (n=19,20,17)	-16.933 Millimeters of mercury Standard Deviation 18.362	-14.267 Millimeters of mercury Standard Deviation 16.993	-18.684 Millimeters of mercury Standard Deviation 20.086
Change From Baseline in Mean Blood Pressure (MBP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 Hour Change at 24 hour (n= 19,20,16)	-16.590 Millimeters of mercury Standard Deviation 19.882	-12.162 Millimeters of mercury Standard Deviation 17.803	-11.135 Millimeters of mercury Standard Deviation 12.593

Measure	Nesiritide (1+ 0.01) n=19 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) n=20 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) n=17 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.
Change From Baseline in Cardiac Index (CI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Baseline (n=19,20,17)	2.712 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.826	2.356 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.527	2.382 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.549
Change From Baseline in Cardiac Index (CI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 0.25 hour (n=19,19,17)	0.199 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.442	0.305 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.395	0.232 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.540
Change From Baseline in Cardiac Index (CI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 0.5 hour (n=19,20,17)	0.239 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.357	0.443 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.451	0.861 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.783
Change From Baseline in Cardiac Index (CI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 1 hour (n=19,20,17)	0.226 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.555	0.445 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.404	0.695 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.443
Change From Baseline in Cardiac Index (CI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 1.5 hour (n=19,20,17)	0.166 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.673	0.293 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.477	0.439 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.603
Change From Baseline in Cardiac Index (CI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 2 hour (n=19,20,17)	0.143 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.758	0.165 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.535	0.216 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.459
Change From Baseline in Cardiac Index (CI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 2.5 hour (n=19,20,17)	-0.175 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.672	0.042 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.425	0.158 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.492
Change From Baseline in Cardiac Index (CI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 3 hour (n=19,20,17)	-0.011 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.613	0.092 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.388	0.029 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.560
Change From Baseline in Cardiac Index (CI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 4 hour (n=19,19,17)	-0.153 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.556	0.055 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.431	0.131 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.324
Change From Baseline in Cardiac Index (CI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 5 hour (n=18,19,17)	-0.212 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.733	0.061 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.329	0.153 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.572
Change From Baseline in Cardiac Index (CI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 6 hour (n=18,19,17)	-0.307 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.732	-0.127 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.368	0.103 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.622
Change From Baseline in Cardiac Index (CI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 9 hour (n=0,1,0)	NA Liter per minute per meter^2 (l/min/m^2) Standard Deviation NA No participant was analyzed for this time point	0.185 Liter per minute per meter^2 (l/min/m^2) Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	NA Liter per minute per meter^2 (l/min/m^2) Standard Deviation NA No participant was analyzed for this time point
Change From Baseline in Cardiac Index (CI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 12 hour (n=16,19,17)	-0.318 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.518	-0.201 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.370	0.185 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.780
Change From Baseline in Cardiac Index (CI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 15 hour (n=2,1,0)	-0.274 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.331	0.186 Liter per minute per meter^2 (l/min/m^2) Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	NA Liter per minute per meter^2 (l/min/m^2) Standard Deviation NA No participant was analyzed for this time point
Change From Baseline in Cardiac Index (CI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 24 hour (n= 14,19,15)	0.054 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.617	-0.199 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.507	0.148 Liter per minute per meter^2 (l/min/m^2) Standard Deviation 0.754

Measure	Nesiritide (1+ 0.01) n=17 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) n=19 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) n=17 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.
Change From Baseline in Stroke Volume Index (SVI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 2.5 hour n=17,19,17)	0.394 milliliter per meter^2 Standard Deviation 7.126	1.501 milliliter per meter^2 Standard Deviation 6.587	3.052 milliliter per meter^2 Standard Deviation 5.474
Change From Baseline in Stroke Volume Index (SVI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 3 hour (n=17,19,17)	2.751 milliliter per meter^2 Standard Deviation 6.960	1.781 milliliter per meter^2 Standard Deviation 5.369	2.091 milliliter per meter^2 Standard Deviation 5.535
Change From Baseline in Stroke Volume Index (SVI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Baseline (n=17,19,17)	29.683 milliliter per meter^2 Standard Deviation 11.141	28.655 milliliter per meter^2 Standard Deviation 9.810	24.483 milliliter per meter^2 Standard Deviation 6.016
Change From Baseline in Stroke Volume Index (SVI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 0.25 hour (n=17,18,17)	2.888 milliliter per meter^2 Standard Deviation 5.948	1.853 milliliter per meter^2 Standard Deviation 4.525	2.584 milliliter per meter^2 Standard Deviation 5.200
Change From Baseline in Stroke Volume Index (SVI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 0.5 hour (n=17,19,17)	4.116 milliliter per meter^2 Standard Deviation 5.692	3.775 milliliter per meter^2 Standard Deviation 6.143	9.191 milliliter per meter^2 Standard Deviation 8.552
Change From Baseline in Stroke Volume Index (SVI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 1 hour (n=17,19,17)	3.904 milliliter per meter^2 Standard Deviation 5.927	4.892 milliliter per meter^2 Standard Deviation 4.766	8.007 milliliter per meter^2 Standard Deviation 4.936
Change From Baseline in Stroke Volume Index (SVI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 1.5 hour (n=17,19,17)	2.822 milliliter per meter^2 Standard Deviation 7.127	3.900 milliliter per meter^2 Standard Deviation 5.161	4.948 milliliter per meter^2 Standard Deviation 5.142
Change From Baseline in Stroke Volume Index (SVI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 2 hour (n=17,19,17)	3.196 milliliter per meter^2 Standard Deviation 7.954	3.526 milliliter per meter^2 Standard Deviation 7.903	3.760 milliliter per meter^2 Standard Deviation 5.210
Change From Baseline in Stroke Volume Index (SVI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 4 hour (n=17,18,17)	1.097 milliliter per meter^2 Standard Deviation 5.952	1.494 milliliter per meter^2 Standard Deviation 5.568	3.142 milliliter per meter^2 Standard Deviation 3.461
Change From Baseline in Stroke Volume Index (SVI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 5 hour (n=16,18,17)	0.525 milliliter per meter^2 Standard Deviation 9.552	2.427 milliliter per meter^2 Standard Deviation 4.530	4.146 milliliter per meter^2 Standard Deviation 6.125
Change From Baseline in Stroke Volume Index (SVI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 6 hour (n=16,18,17)	0.320 milliliter per meter^2 Standard Deviation 8.458	1.421 milliliter per meter^2 Standard Deviation 7.082	3.319 milliliter per meter^2 Standard Deviation 6.079
Change From Baseline in Stroke Volume Index (SVI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 9 hour (n=0,1,0)	NA milliliter per meter^2 Standard Deviation NA No participant was analyzed for this time point	4.657 milliliter per meter^2 Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	NA milliliter per meter^2 Standard Deviation NA No participant was analyzed for this time point
Change From Baseline in Stroke Volume Index (SVI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 12 hour (n=15,18,17)	1.100 milliliter per meter^2 Standard Deviation 8.143	-0.912 milliliter per meter^2 Standard Deviation 6.992	5.610 milliliter per meter^2 Standard Deviation 8.298
Change From Baseline in Stroke Volume Index (SVI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 15 hour (n=2,1,0)	-3.357 milliliter per meter^2 Standard Deviation 0.593	-0.592 milliliter per meter^2 Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	NA milliliter per meter^2 Standard Deviation NA No participant was analyzed for this time point
Change From Baseline in Stroke Volume Index (SVI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 24 hour (n=13,18,15)	1.690 milliliter per meter^2 Standard Deviation 9.763	-0.808 milliliter per meter^2 Standard Deviation 7.217	0.590 milliliter per meter^2 Standard Deviation 6.884

Measure	Nesiritide (1+ 0.01) n=14 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 15.4 to 35.2 mcg/kg.	Nesiritide (2+0.005) n=18 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 9.2 to 31.7 mcg/kg.	Nesiritide (2+0.01) n=14 Participants Intravenous bolus treatment was administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which was comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage were increased by 0.005 mcg/kg/min every 3 hours. Total dosage administered was 16.4 to 36.2 mcg/kg.
Change From Baseline in Pulmonary Vascular Resistance (PVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 6 hour (n=12,17,12)	50.780 dyne*second/centimeter^5 Standard Deviation 117.927	10.104 dyne*second/centimeter^5 Standard Deviation 94.079	-4.627 dyne*second/centimeter^5 Standard Deviation 107.473
Change From Baseline in Pulmonary Vascular Resistance (PVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Baseline (n=14,18,14)	215.736 dyne*second/centimeter^5 Standard Deviation 124.776	208.714 dyne*second/centimeter^5 Standard Deviation 166.213	239.383 dyne*second/centimeter^5 Standard Deviation 122.453
Change From Baseline in Pulmonary Vascular Resistance (PVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 0.25 hour (n=14,17,13)	-19.361 dyne*second/centimeter^5 Standard Deviation 79.932	-40.647 dyne*second/centimeter^5 Standard Deviation 97.780	-12.482 dyne*second/centimeter^5 Standard Deviation 86.016
Change From Baseline in Pulmonary Vascular Resistance (PVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 0.5 hour (n=14,18,13)	-12.954 dyne*second/centimeter^5 Standard Deviation 70.125	-23.263 dyne*second/centimeter^5 Standard Deviation 141.171	-34.144 dyne*second/centimeter^5 Standard Deviation 100.492
Change From Baseline in Pulmonary Vascular Resistance (PVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 1 hour (n=14,18,12)	-0.991 dyne*second/centimeter^5 Standard Deviation 93.305	1.964 dyne*second/centimeter^5 Standard Deviation 110.283	-44.337 dyne*second/centimeter^5 Standard Deviation 116.971
Change From Baseline in Pulmonary Vascular Resistance (PVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 1.5 hour (n=14,18,12)	19.161 dyne*second/centimeter^5 Standard Deviation 57.701	-2.975 dyne*second/centimeter^5 Standard Deviation 93.034	-34.079 dyne*second/centimeter^5 Standard Deviation 109.876
Change From Baseline in Pulmonary Vascular Resistance (PVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 2 hour (n=14,18,12)	11.083 dyne*second/centimeter^5 Standard Deviation 69.935	23.400 dyne*second/centimeter^5 Standard Deviation 116.715	-2.991 dyne*second/centimeter^5 Standard Deviation 104.337
Change From Baseline in Pulmonary Vascular Resistance (PVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 2.5 hour (n=14,18,12)	32.991 dyne*second/centimeter^5 Standard Deviation 59.277	11.609 dyne*second/centimeter^5 Standard Deviation 106.732	1.610 dyne*second/centimeter^5 Standard Deviation 107.365
Change From Baseline in Pulmonary Vascular Resistance (PVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 3 hour (n=14,18,12)	6.691 dyne*second/centimeter^5 Standard Deviation 88.625	-2.667 dyne*second/centimeter^5 Standard Deviation 122.330	11.381 dyne*second/centimeter^5 Standard Deviation 109.961
Change From Baseline in Pulmonary Vascular Resistance (PVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 4 hour (n=14,17,12)	12.217 dyne*second/centimeter^5 Standard Deviation 103.059	3.797 dyne*second/centimeter^5 Standard Deviation 128.528	-30.437 dyne*second/centimeter^5 Standard Deviation 89.235
Change From Baseline in Pulmonary Vascular Resistance (PVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 5 hour (n=12,17,12)	30.161 dyne*second/centimeter^5 Standard Deviation 73.755	-10.958 dyne*second/centimeter^5 Standard Deviation 87.255	-21.678 dyne*second/centimeter^5 Standard Deviation 97.090
Change From Baseline in Pulmonary Vascular Resistance (PVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 9 hour (n=0,1,0)	NA dyne*second/centimeter^5 Standard Deviation NA No participant was analyzed for this time point	2.017 dyne*second/centimeter^5 Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	NA dyne*second/centimeter^5 Standard Deviation NA No participant was analyzed for this time point
Change From Baseline in Pulmonary Vascular Resistance (PVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 12 hour (n=10,17,12)	42.717 dyne*second/centimeter^5 Standard Deviation 116.928	20.625 dyne*second/centimeter^5 Standard Deviation 109.345	-18.302 dyne*second/centimeter^5 Standard Deviation 132.041
Change From Baseline in Pulmonary Vascular Resistance (PVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 15 hour (n=1,1,0)	46.681 dyne*second/centimeter^5 Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	116.667 dyne*second/centimeter^5 Standard Deviation NA Standard deviation was not estimable because number of participant analyzed for this time point is 1	NA dyne*second/centimeter^5 Standard Deviation NA No participant was analyzed for this time point
Change From Baseline in Pulmonary Vascular Resistance (PVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour Change at 24 hour (n=9,17,10)	32.656 dyne*second/centimeter^5 Standard Deviation 76.762	-29.072 dyne*second/centimeter^5 Standard Deviation 133.105	-37.891 dyne*second/centimeter^5 Standard Deviation 137.587