Trial Outcomes & Findings for Human B-type Natriuretic Peptide (BNP) (Nesiritide) to Help Heart, Kidney, and Hormonal Functions in Persons With Lower Heart Pumping Function (NCT NCT00405639)

NCT ID: NCT00405639

Last Updated: 2014-03-17

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 37 participants
• Primary outcome timeframe: baseline, 12 weeks
• Results posted on: 2014-03-17

Participant Flow

All subjects were recruited from the Mayo Clinic in Rochester, Minnesota.

Participant milestones

Measure	Nesiritide Subjects randomized to this arm will receive 5 microgram/Kg subcutaneous (SQ) injection of nesiritide on Day 1. If after the first SQ injection the subject's systolic blood pressure is \>90 mmHG and no symptoms of hypotension, then the second dose can be increased to 10 microgram/Kg. Subjects will self-administer the second dose 12 hours after the first dose, then self-administer the third dose 12 hours after the second dose. Subjects will be dismissed with instructions and supplies for 6 weeks of SQ administration twice a day. After 6 weeks, the subjects will return to the lab for assessments, and will be dismissed with supplies for 6 more weeks of SQ administration twice a day.	Placebo Subjects randomized to this arm will receive self administered SQ placebo (normal saline) injections to match those of the study drug group. That is, first dose on Day 1, second dose 12 hours after the first dose, third dose 12 hours after the second dose. Subjects will be dismissed with instructions and supplies for 6 weeks of SQ administration twice a day. After 6 weeks, the subjects will return to the lab for assessments, and will be dismissed with supplies for 6 more weeks of SQ administration twice a day.
Overall Study STARTED	25	12
Overall Study COMPLETED	22	12
Overall Study NOT COMPLETED	3	0

Reasons for withdrawal

Measure	Nesiritide Subjects randomized to this arm will receive 5 microgram/Kg subcutaneous (SQ) injection of nesiritide on Day 1. If after the first SQ injection the subject's systolic blood pressure is \>90 mmHG and no symptoms of hypotension, then the second dose can be increased to 10 microgram/Kg. Subjects will self-administer the second dose 12 hours after the first dose, then self-administer the third dose 12 hours after the second dose. Subjects will be dismissed with instructions and supplies for 6 weeks of SQ administration twice a day. After 6 weeks, the subjects will return to the lab for assessments, and will be dismissed with supplies for 6 more weeks of SQ administration twice a day.	Placebo Subjects randomized to this arm will receive self administered SQ placebo (normal saline) injections to match those of the study drug group. That is, first dose on Day 1, second dose 12 hours after the first dose, third dose 12 hours after the second dose. Subjects will be dismissed with instructions and supplies for 6 weeks of SQ administration twice a day. After 6 weeks, the subjects will return to the lab for assessments, and will be dismissed with supplies for 6 more weeks of SQ administration twice a day.
Overall Study Withdrawal by Subject	1	0
Overall Study Adverse Event	1	0
Overall Study Seizure prior to receiving BNP	1	0

Baseline Characteristics

Human B-type Natriuretic Peptide (BNP) (Nesiritide) to Help Heart, Kidney, and Hormonal Functions in Persons With Lower Heart Pumping Function

Baseline characteristics by cohort

Measure	Nesiritide n=25 Participants Subjects randomized to this arm will receive 5 microgram/Kg subcutaneous (SQ) injection of nesiritide on Day 1. If after the first SQ injection the subject's systolic blood pressure is \>90 mmHG and no symptoms of hypotension, then the second dose can be increased to 10 microgram/Kg. Subjects will self-administer the second dose 12 hours after the first dose, then self-administer the third dose 12 hours after the second dose. Subjects will be dismissed with instructions and supplies for 6 weeks of SQ administration twice a day. After 6 weeks, the subjects will return to the lab for assessments, and will be dismissed with supplies for 6 more weeks of SQ administration twice a day.	Placebo n=12 Participants Subjects randomized to this arm will receive self administered SQ placebo (normal saline) injections to match those of the study drug group. That is, first dose on Day 1, second dose 12 hours after the first dose, third dose 12 hours after the second dose. Subjects will be dismissed with instructions and supplies for 6 weeks of SQ administration twice a day. After 6 weeks, the subjects will return to the lab for assessments, and will be dismissed with supplies for 6 more weeks of SQ administration twice a day.	Total n=37 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=5 Participants	8 Participants n=7 Participants	19 Participants n=5 Participants
Age, Categorical >=65 years	14 Participants n=5 Participants	4 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	10 Participants n=7 Participants	32 Participants n=5 Participants
Region of Enrollment United States	25 participants n=5 Participants	12 participants n=7 Participants	37 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline, 12 weeks

Outcome measures

Measure	Nesiritide n=22 Participants Subjects randomized to this arm will receive 5 microgram/Kg subcutaneous (SQ) injection of nesiritide on Day 1. If after the first SQ injection the subject's systolic blood pressure is \>90 mmHG and no symptoms of hypotension, then the second dose can be increased to 10 microgram/Kg. Subjects will self-administer the second dose 12 hours after the first dose, then self-administer the third dose 12 hours after the second dose. Subjects will be dismissed with instructions and supplies for 6 weeks of SQ administration twice a day. After 6 weeks, the subjects will return to the lab for assessments, and will be dismissed with supplies for 6 more weeks of SQ administration twice a day.	Placebo n=12 Participants Subjects randomized to this arm will receive self administered SQ placebo (normal saline) injections to match those of the study drug group. That is, first dose on Day 1, second dose 12 hours after the first dose, third dose 12 hours after the second dose. Subjects will be dismissed with instructions and supplies for 6 weeks of SQ administration twice a day. After 6 weeks, the subjects will return to the lab for assessments, and will be dismissed with supplies for 6 more weeks of SQ administration twice a day.
Change in Urinary Sodium Excretion in Response to Saline Load	179.1 mEq/min Standard Deviation 252.2	3.1 mEq/min Standard Deviation 102.4

SECONDARY outcome

Timeframe: baseline, 12 weeks

Outcome measures

Measure	Nesiritide n=22 Participants Subjects randomized to this arm will receive 5 microgram/Kg subcutaneous (SQ) injection of nesiritide on Day 1. If after the first SQ injection the subject's systolic blood pressure is \>90 mmHG and no symptoms of hypotension, then the second dose can be increased to 10 microgram/Kg. Subjects will self-administer the second dose 12 hours after the first dose, then self-administer the third dose 12 hours after the second dose. Subjects will be dismissed with instructions and supplies for 6 weeks of SQ administration twice a day. After 6 weeks, the subjects will return to the lab for assessments, and will be dismissed with supplies for 6 more weeks of SQ administration twice a day.	Placebo n=12 Participants Subjects randomized to this arm will receive self administered SQ placebo (normal saline) injections to match those of the study drug group. That is, first dose on Day 1, second dose 12 hours after the first dose, third dose 12 hours after the second dose. Subjects will be dismissed with instructions and supplies for 6 weeks of SQ administration twice a day. After 6 weeks, the subjects will return to the lab for assessments, and will be dismissed with supplies for 6 more weeks of SQ administration twice a day.
Change in Urine Flow in Response to Saline Load	3.1 ml/min Standard Deviation 3.8	-0.4 ml/min Standard Deviation 2.1

SECONDARY outcome

Timeframe: baseline, 12 weeks

Kidney function was measured by GFR determined by iothalamate clearance. GFR describes the flow rate of filtered fluid through the kidney measured in milliliters per minute per 1.73 m^2 of body surface area. A lower GFR means the kidney is not filtering normally. An estimated GFR of less than 60 mg/min/1.73 m^2 of body surface area is considered to be impaired kidney function.

Outcome measures

Measure	Nesiritide n=22 Participants Subjects randomized to this arm will receive 5 microgram/Kg subcutaneous (SQ) injection of nesiritide on Day 1. If after the first SQ injection the subject's systolic blood pressure is \>90 mmHG and no symptoms of hypotension, then the second dose can be increased to 10 microgram/Kg. Subjects will self-administer the second dose 12 hours after the first dose, then self-administer the third dose 12 hours after the second dose. Subjects will be dismissed with instructions and supplies for 6 weeks of SQ administration twice a day. After 6 weeks, the subjects will return to the lab for assessments, and will be dismissed with supplies for 6 more weeks of SQ administration twice a day.	Placebo n=12 Participants Subjects randomized to this arm will receive self administered SQ placebo (normal saline) injections to match those of the study drug group. That is, first dose on Day 1, second dose 12 hours after the first dose, third dose 12 hours after the second dose. Subjects will be dismissed with instructions and supplies for 6 weeks of SQ administration twice a day. After 6 weeks, the subjects will return to the lab for assessments, and will be dismissed with supplies for 6 more weeks of SQ administration twice a day.
Change in Renal Function as Measured by Glomerular Filtration Rate (GFR) in Response to Saline Load	1.6 ml/min/1.73 m^2 Standard Deviation 9.7	-7.4 ml/min/1.73 m^2 Standard Deviation 12.5

SECONDARY outcome

Timeframe: baseline, 12 weeks

Left ventricular mass index (LVMI) is a surrogate of left ventricular hypertrophy and a predictor of cardiac morbidity and mortality in adults with hypertension. LVMI was measured with echocardiography, indexed to body surface area estimated by left ventricular (LV) cavity dimension and wall thickness at end-diastole.

Outcome measures

Measure	Nesiritide n=22 Participants Subjects randomized to this arm will receive 5 microgram/Kg subcutaneous (SQ) injection of nesiritide on Day 1. If after the first SQ injection the subject's systolic blood pressure is \>90 mmHG and no symptoms of hypotension, then the second dose can be increased to 10 microgram/Kg. Subjects will self-administer the second dose 12 hours after the first dose, then self-administer the third dose 12 hours after the second dose. Subjects will be dismissed with instructions and supplies for 6 weeks of SQ administration twice a day. After 6 weeks, the subjects will return to the lab for assessments, and will be dismissed with supplies for 6 more weeks of SQ administration twice a day.	Placebo n=12 Participants Subjects randomized to this arm will receive self administered SQ placebo (normal saline) injections to match those of the study drug group. That is, first dose on Day 1, second dose 12 hours after the first dose, third dose 12 hours after the second dose. Subjects will be dismissed with instructions and supplies for 6 weeks of SQ administration twice a day. After 6 weeks, the subjects will return to the lab for assessments, and will be dismissed with supplies for 6 more weeks of SQ administration twice a day.
Change in Left Ventricular Mass Index	-5.8 g/m^2 Standard Deviation 15.7	2.0 g/m^2 Standard Deviation 5.4

Adverse Events

Nesiritide

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Nesiritide n=22 participants at risk Subjects randomized to this arm will receive 5 microgram/Kg subcutaneous (SQ) injection of nesiritide on Day 1. If after the first SQ injection the subject's systolic blood pressure is \>90 mmHG and no symptoms of hypotension, then the second dose can be increased to 10 microgram/Kg. Subjects will self-administer the second dose 12 hours after the first dose, then self-administer the third dose 12 hours after the second dose. Subjects will be dismissed with instructions and supplies for 6 weeks of SQ administration twice a day. After 6 weeks, the subjects will return to the lab for assessments, and will be dismissed with supplies for 6 more weeks of SQ administration twice a day.	Placebo n=12 participants at risk Subjects randomized to this arm will receive self administered SQ placebo (normal saline) injections to match those of the study drug group. That is, first dose on Day 1, second dose 12 hours after the first dose, third dose 12 hours after the second dose. Subjects will be dismissed with instructions and supplies for 6 weeks of SQ administration twice a day. After 6 weeks, the subjects will return to the lab for assessments, and will be dismissed with supplies for 6 more weeks of SQ administration twice a day.
Eye disorders Blurring Vision	0.00% 0/22 • Subjects will be followed for the 12 weeks while on study.	8.3% 1/12 • Number of events 1 • Subjects will be followed for the 12 weeks while on study.
Investigations Hypotension	27.3% 6/22 • Number of events 6 • Subjects will be followed for the 12 weeks while on study.	8.3% 1/12 • Number of events 1 • Subjects will be followed for the 12 weeks while on study.
Nervous system disorders Flank pain	4.5% 1/22 • Number of events 1 • Subjects will be followed for the 12 weeks while on study.	0.00% 0/12 • Subjects will be followed for the 12 weeks while on study.
General disorders Gout	4.5% 1/22 • Number of events 1 • Subjects will be followed for the 12 weeks while on study.	0.00% 0/12 • Subjects will be followed for the 12 weeks while on study.
Cardiac disorders Heart Failure symptoms	9.1% 2/22 • Number of events 2 • Subjects will be followed for the 12 weeks while on study.	0.00% 0/12 • Subjects will be followed for the 12 weeks while on study.
Vascular disorders Hyperkalemia	4.5% 1/22 • Number of events 1 • Subjects will be followed for the 12 weeks while on study.	8.3% 1/12 • Number of events 1 • Subjects will be followed for the 12 weeks while on study.
Cardiac disorders Tachycardia	9.1% 2/22 • Number of events 2 • Subjects will be followed for the 12 weeks while on study.	0.00% 0/12 • Subjects will be followed for the 12 weeks while on study.
Vascular disorders Thromboembolism	0.00% 0/22 • Subjects will be followed for the 12 weeks while on study.	8.3% 1/12 • Number of events 1 • Subjects will be followed for the 12 weeks while on study.
Renal and urinary disorders Urinary Tract Infection	0.00% 0/22 • Subjects will be followed for the 12 weeks while on study.	8.3% 1/12 • Number of events 1 • Subjects will be followed for the 12 weeks while on study.
General disorders Hospitalization	4.5% 1/22 • Number of events 1 • Subjects will be followed for the 12 weeks while on study.	0.00% 0/12 • Subjects will be followed for the 12 weeks while on study.

Additional Information

Dr. Horng H. Chen

Mayo Clinic

Phone: 507-538-2354

Email: chen.horng@mayo.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place