Trial Outcomes & Findings for Effects of Perioperative Nesiritide or Milrinone Infusion on Recovery From Fontan Surgery (NCT NCT00543309)

NCT ID: NCT00543309

Last Updated: 2018-06-25

Results Overview

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 106 participants
• Primary outcome timeframe: 30 days
• Results posted on: 2018-06-25

Participant Flow

Recruitment period: October 2007 - January 2013. Location: Cardiac operating rooms and cardiac intensive care unit (CICU) at Boston Children's Hospital

Participant milestones

Measure	I- Nesiritide Patients assigned to the nesiritide group will receive an intravenous loading dose of 2 mcg/kg followed by an infusion of 0.015 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. nesiritide: Nesiritide bolus 2 mcg/kg on cardiopulmonary bypass (CPB), then infusion of 0.015 mcg/kg/min. infusion dose may be adjusted	II- Milrinone Patients assigned to the milrinone group will receive a bolus of 50 mcg/kg followed by an infusion of 0.5 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. milrinone: Milrinone 50 mcg/kg bolus on CPB, the infusion of 0.5 mcg/kg/min. Infusion rate may be adjusted	III- Placebo Patients assigned to the placebo group will receive a 0.33 mL/kg bolus of 5% dextrose in water (D5W), followed by an infusion of D5W, administered for at least 12 hours after CICU admission and up to five days, unless prespecified lack of efficacy criteria are met. placebo: Placebo bolus on CPB, then placebo infusion
Overall Study STARTED	35	36	35
Overall Study COMPLETED	35	35	35
Overall Study NOT COMPLETED	0	1	0

Reasons for withdrawal

Measure	I- Nesiritide Patients assigned to the nesiritide group will receive an intravenous loading dose of 2 mcg/kg followed by an infusion of 0.015 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. nesiritide: Nesiritide bolus 2 mcg/kg on cardiopulmonary bypass (CPB), then infusion of 0.015 mcg/kg/min. infusion dose may be adjusted	II- Milrinone Patients assigned to the milrinone group will receive a bolus of 50 mcg/kg followed by an infusion of 0.5 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. milrinone: Milrinone 50 mcg/kg bolus on CPB, the infusion of 0.5 mcg/kg/min. Infusion rate may be adjusted	III- Placebo Patients assigned to the placebo group will receive a 0.33 mL/kg bolus of 5% dextrose in water (D5W), followed by an infusion of D5W, administered for at least 12 hours after CICU admission and up to five days, unless prespecified lack of efficacy criteria are met. placebo: Placebo bolus on CPB, then placebo infusion
Overall Study Physician Decision	0	1	0

Baseline Characteristics

Effects of Perioperative Nesiritide or Milrinone Infusion on Recovery From Fontan Surgery

Baseline characteristics by cohort

Measure	I- Nesiritide n=35 Participants Patients assigned to the nesiritide group will receive an intravenous loading dose of 2 mcg/kg followed by an infusion of 0.015 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. nesiritide: Nesiritide bolus 2 mcg/kg on CPB, then infusion of 0.015 mcg/kg/min. infusion dose may be adjusted	II- Milrinone n=36 Participants Patients assigned to the milrinone group will receive a bolus of 50 mcg/kg followed by an infusion of 0.5 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. milrinone: Milrinone 50 mcg/kg bolus on CPB, the infusion of 0.5 mcg/kg/min. Infusion rate may be adjusted	III- Placebo n=35 Participants Patients assigned to the placebo group will receive a 0.33 mL/kg bolus of 5% dextrose in water (D5W), followed by an infusion of D5W, administered for at least 12 hours after CICU admission and up to five days, unless prespecified lack of efficacy criteria are met. placebo: Placebo bolus on CPB, then placebo infusion	Total n=106 Participants Total of all reporting groups
Age, Continuous	2.7 years n=5 Participants	2.6 years n=7 Participants	2.7 years n=5 Participants	2.7 years n=4 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	17 Participants n=7 Participants	12 Participants n=5 Participants	44 Participants n=4 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	19 Participants n=7 Participants	23 Participants n=5 Participants	62 Participants n=4 Participants
Race/Ethnicity, Customized Race · White	28 Participants n=5 Participants	24 Participants n=7 Participants	22 Participants n=5 Participants	74 Participants n=4 Participants
Race/Ethnicity, Customized Race · Black	3 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants
Race/Ethnicity, Customized Race · Hispanic/Latino	3 Participants n=5 Participants	7 Participants n=7 Participants	5 Participants n=5 Participants	15 Participants n=4 Participants
Race/Ethnicity, Customized Race · Asian	0 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized Race · More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Race · Other	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment United States	35 Participants n=5 Participants	36 Participants n=7 Participants	35 Participants n=5 Participants	106 Participants n=4 Participants
Weight	12.5 kilograms n=5 Participants	12.8 kilograms n=7 Participants	12.6 kilograms n=5 Participants	12.6 kilograms n=4 Participants
Ventricular Morphology Left dominant	15 Participants n=5 Participants	10 Participants n=7 Participants	12 Participants n=5 Participants	37 Participants n=4 Participants
Ventricular Morphology Right dominant	20 Participants n=5 Participants	25 Participants n=7 Participants	22 Participants n=5 Participants	67 Participants n=4 Participants
Ventricular Morphology Two ventricles	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Prior Cardiac Operations	2 operations n=5 Participants	2 operations n=7 Participants	2 operations n=5 Participants	2 operations n=4 Participants
Prior Interventional Cardiac Catheterization	28 Participants n=5 Participants	30 Participants n=7 Participants	30 Participants n=5 Participants	88 Participants n=4 Participants
History of Arrhythmias	9 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	16 Participants n=4 Participants
Noncardiac congenital anomaly	4 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	17 Participants n=4 Participants
Chromosomal abnormality or syndrome	3 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants

PRIMARY outcome

Timeframe: 30 days

Outcome measures

Measure	I- Nesiritide n=35 Participants Patients assigned to the nesiritide group will receive an intravenous loading dose of 2 mcg/kg followed by an infusion of 0.015 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. nesiritide: Nesiritide bolus 2 mcg/kg on CPB, then infusion of 0.015 mcg/kg/min. infusion dose may be adjusted	II- Milrinone n=36 Participants Patients assigned to the milrinone group will receive a bolus of 50 mcg/kg followed by an infusion of 0.5 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. milrinone: Milrinone 50 mcg/kg bolus on CPB, the infusion of 0.5 mcg/kg/min. Infusion rate may be adjusted	III- Placebo n=35 Participants Patients assigned to the placebo group will receive a 0.33 mL/kg bolus of 5% dextrose in water (D5W), followed by an infusion of D5W, administered for at least 12 hours after CICU admission and up to five days, unless prespecified lack of efficacy criteria are met. placebo: Placebo bolus on CPB, then placebo infusion
Days Alive and Out of the Hospital Within 30 Days of Surgery.	20 days Interval 0.0 to 24.0	18 days Interval 0.0 to 23.0	20 days Interval 0.0 to 23.0

SECONDARY outcome

Timeframe: Postoperative hour #1

Population: Study patients for whom cardiac index measurements were available.

Cardiac index measured using Fick principle with measured oxygen consumption.

Outcome measures

Measure	I- Nesiritide n=23 Participants Patients assigned to the nesiritide group will receive an intravenous loading dose of 2 mcg/kg followed by an infusion of 0.015 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. nesiritide: Nesiritide bolus 2 mcg/kg on CPB, then infusion of 0.015 mcg/kg/min. infusion dose may be adjusted	II- Milrinone n=24 Participants Patients assigned to the milrinone group will receive a bolus of 50 mcg/kg followed by an infusion of 0.5 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. milrinone: Milrinone 50 mcg/kg bolus on CPB, the infusion of 0.5 mcg/kg/min. Infusion rate may be adjusted	III- Placebo n=24 Participants Patients assigned to the placebo group will receive a 0.33 mL/kg bolus of 5% dextrose in water (D5W), followed by an infusion of D5W, administered for at least 12 hours after CICU admission and up to five days, unless prespecified lack of efficacy criteria are met. placebo: Placebo bolus on CPB, then placebo infusion
Cardiovascular: Cardiac Index	3.5 L/min/m2 Interval 1.5 to 6.1	2.8 L/min/m2 Interval 1.6 to 6.3	2.5 L/min/m2 Interval 1.5 to 6.1

SECONDARY outcome

Timeframe: Postoperative hour #8

Population: Study patients for whom cardiac index measurements were available.

Cardiac index measured using Fick principle with measured oxygen consumption.

Outcome measures

Measure	I- Nesiritide n=25 Participants Patients assigned to the nesiritide group will receive an intravenous loading dose of 2 mcg/kg followed by an infusion of 0.015 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. nesiritide: Nesiritide bolus 2 mcg/kg on CPB, then infusion of 0.015 mcg/kg/min. infusion dose may be adjusted	II- Milrinone n=24 Participants Patients assigned to the milrinone group will receive a bolus of 50 mcg/kg followed by an infusion of 0.5 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. milrinone: Milrinone 50 mcg/kg bolus on CPB, the infusion of 0.5 mcg/kg/min. Infusion rate may be adjusted	III- Placebo n=23 Participants Patients assigned to the placebo group will receive a 0.33 mL/kg bolus of 5% dextrose in water (D5W), followed by an infusion of D5W, administered for at least 12 hours after CICU admission and up to five days, unless prespecified lack of efficacy criteria are met. placebo: Placebo bolus on CPB, then placebo infusion
Cardiovascular: Cardiac Index	3.2 L/min/m2 Interval 0.6 to 6.7	2.9 L/min/m2 Interval 0.9 to 5.9	2.5 L/min/m2 Interval 1.0 to 5.5

SECONDARY outcome

Timeframe: Postoperative day (POD) #0 through 5

arrhythmia lasting >30 seconds or requiring treatment

Outcome measures

Measure	I- Nesiritide n=35 Participants Patients assigned to the nesiritide group will receive an intravenous loading dose of 2 mcg/kg followed by an infusion of 0.015 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. nesiritide: Nesiritide bolus 2 mcg/kg on CPB, then infusion of 0.015 mcg/kg/min. infusion dose may be adjusted	II- Milrinone n=36 Participants Patients assigned to the milrinone group will receive a bolus of 50 mcg/kg followed by an infusion of 0.5 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. milrinone: Milrinone 50 mcg/kg bolus on CPB, the infusion of 0.5 mcg/kg/min. Infusion rate may be adjusted	III- Placebo n=35 Participants Patients assigned to the placebo group will receive a 0.33 mL/kg bolus of 5% dextrose in water (D5W), followed by an infusion of D5W, administered for at least 12 hours after CICU admission and up to five days, unless prespecified lack of efficacy criteria are met. placebo: Placebo bolus on CPB, then placebo infusion
Cardiovascular: Arrhythmia	16 Participants	21 Participants	13 Participants

SECONDARY outcome

Timeframe: Initial 24 hours in CICU

Peak Inotrope Score = Doses of dopamine in mcg/kg/minute + dobutamine in mcg/kg/minute + (epinephrine in mcg/kg/minute x 100).

The lowest (best) possible Peak Inotrope Score = 0 dose equivalents. There is no maximum Peak Inotrope Score.

Outcome measures

Measure	I- Nesiritide n=35 Participants Patients assigned to the nesiritide group will receive an intravenous loading dose of 2 mcg/kg followed by an infusion of 0.015 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. nesiritide: Nesiritide bolus 2 mcg/kg on CPB, then infusion of 0.015 mcg/kg/min. infusion dose may be adjusted	II- Milrinone n=36 Participants Patients assigned to the milrinone group will receive a bolus of 50 mcg/kg followed by an infusion of 0.5 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. milrinone: Milrinone 50 mcg/kg bolus on CPB, the infusion of 0.5 mcg/kg/min. Infusion rate may be adjusted	III- Placebo n=35 Participants Patients assigned to the placebo group will receive a 0.33 mL/kg bolus of 5% dextrose in water (D5W), followed by an infusion of D5W, administered for at least 12 hours after CICU admission and up to five days, unless prespecified lack of efficacy criteria are met. placebo: Placebo bolus on CPB, then placebo infusion
Cardiovascular: Peak Inotrope Score	5 dose equivalents Interval 0.0 to 15.0	5 dose equivalents Interval 0.0 to 16.0	5 dose equivalents Interval 0.0 to 15.0

SECONDARY outcome

Timeframe: Initial 24 hours in CICU

Outcome measures

Measure	I- Nesiritide n=35 Participants Patients assigned to the nesiritide group will receive an intravenous loading dose of 2 mcg/kg followed by an infusion of 0.015 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. nesiritide: Nesiritide bolus 2 mcg/kg on CPB, then infusion of 0.015 mcg/kg/min. infusion dose may be adjusted	II- Milrinone n=36 Participants Patients assigned to the milrinone group will receive a bolus of 50 mcg/kg followed by an infusion of 0.5 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. milrinone: Milrinone 50 mcg/kg bolus on CPB, the infusion of 0.5 mcg/kg/min. Infusion rate may be adjusted	III- Placebo n=35 Participants Patients assigned to the placebo group will receive a 0.33 mL/kg bolus of 5% dextrose in water (D5W), followed by an infusion of D5W, administered for at least 12 hours after CICU admission and up to five days, unless prespecified lack of efficacy criteria are met. placebo: Placebo bolus on CPB, then placebo infusion
Cardiovascular: Peak Lactate Level	2.6 mEq/liter Interval 1.6 to 12.6	3.1 mEq/liter Interval 1.5 to 13.7	3.1 mEq/liter Interval 1.4 to 12.7

SECONDARY outcome

Timeframe: first 24 hours CICU admit

Volume of urine in mL/kg per day

Outcome measures

Measure	I- Nesiritide n=35 Participants Patients assigned to the nesiritide group will receive an intravenous loading dose of 2 mcg/kg followed by an infusion of 0.015 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. nesiritide: Nesiritide bolus 2 mcg/kg on CPB, then infusion of 0.015 mcg/kg/min. infusion dose may be adjusted	II- Milrinone n=35 Participants Patients assigned to the milrinone group will receive a bolus of 50 mcg/kg followed by an infusion of 0.5 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. milrinone: Milrinone 50 mcg/kg bolus on CPB, the infusion of 0.5 mcg/kg/min. Infusion rate may be adjusted	III- Placebo n=35 Participants Patients assigned to the placebo group will receive a 0.33 mL/kg bolus of 5% dextrose in water (D5W), followed by an infusion of D5W, administered for at least 12 hours after CICU admission and up to five days, unless prespecified lack of efficacy criteria are met. placebo: Placebo bolus on CPB, then placebo infusion
Renal Function: Urine Output	43 mL/kg per day Interval 13.0 to 87.0	37 mL/kg per day Interval 13.0 to 94.0	34 mL/kg per day Interval 15.0 to 82.0

SECONDARY outcome

Timeframe: 14 days after surgery

Outcome measures

Measure	I- Nesiritide n=35 Participants Patients assigned to the nesiritide group will receive an intravenous loading dose of 2 mcg/kg followed by an infusion of 0.015 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. nesiritide: Nesiritide bolus 2 mcg/kg on CPB, then infusion of 0.015 mcg/kg/min. infusion dose may be adjusted	II- Milrinone n=36 Participants Patients assigned to the milrinone group will receive a bolus of 50 mcg/kg followed by an infusion of 0.5 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. milrinone: Milrinone 50 mcg/kg bolus on CPB, the infusion of 0.5 mcg/kg/min. Infusion rate may be adjusted	III- Placebo n=35 Participants Patients assigned to the placebo group will receive a 0.33 mL/kg bolus of 5% dextrose in water (D5W), followed by an infusion of D5W, administered for at least 12 hours after CICU admission and up to five days, unless prespecified lack of efficacy criteria are met. placebo: Placebo bolus on CPB, then placebo infusion
Renal Function: Maximum Change in Serum Creatinine	0.1 mg/dL Interval 0.0 to 4.8	0.2 mg/dL Interval 0.0 to 0.6	0.2 mg/dL Interval -0.1 to 0.6

SECONDARY outcome

Timeframe: From Fontan operation until initial extubation, assessed during initial CICU stay, up to 30 days.

Hours of mechanical ventilation until initial extubation following the Fontan operation.

Outcome measures

Measure	I- Nesiritide n=35 Participants Patients assigned to the nesiritide group will receive an intravenous loading dose of 2 mcg/kg followed by an infusion of 0.015 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. nesiritide: Nesiritide bolus 2 mcg/kg on CPB, then infusion of 0.015 mcg/kg/min. infusion dose may be adjusted	II- Milrinone n=36 Participants Patients assigned to the milrinone group will receive a bolus of 50 mcg/kg followed by an infusion of 0.5 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. milrinone: Milrinone 50 mcg/kg bolus on CPB, the infusion of 0.5 mcg/kg/min. Infusion rate may be adjusted	III- Placebo n=35 Participants Patients assigned to the placebo group will receive a 0.33 mL/kg bolus of 5% dextrose in water (D5W), followed by an infusion of D5W, administered for at least 12 hours after CICU admission and up to five days, unless prespecified lack of efficacy criteria are met. placebo: Placebo bolus on CPB, then placebo infusion
Resource Utilization: Hours of Mechanical Ventilation Until Initial Extubation	24 hours Interval 8.0 to 505.0	23 hours Interval 9.0 to 337.0	22 hours Interval 5.0 to 206.0

SECONDARY outcome

Timeframe: From Fontan operation until initial discharge from the CICU, assessed during the postoperative hospitalization, up to 90 days.

Days of initial postoperative CICU care following the Fontan operation.

Outcome measures

Measure	I- Nesiritide n=35 Participants Patients assigned to the nesiritide group will receive an intravenous loading dose of 2 mcg/kg followed by an infusion of 0.015 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. nesiritide: Nesiritide bolus 2 mcg/kg on CPB, then infusion of 0.015 mcg/kg/min. infusion dose may be adjusted	II- Milrinone n=36 Participants Patients assigned to the milrinone group will receive a bolus of 50 mcg/kg followed by an infusion of 0.5 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. milrinone: Milrinone 50 mcg/kg bolus on CPB, the infusion of 0.5 mcg/kg/min. Infusion rate may be adjusted	III- Placebo n=35 Participants Patients assigned to the placebo group will receive a 0.33 mL/kg bolus of 5% dextrose in water (D5W), followed by an infusion of D5W, administered for at least 12 hours after CICU admission and up to five days, unless prespecified lack of efficacy criteria are met. placebo: Placebo bolus on CPB, then placebo infusion
Resource Utilization: Days of Initial CICU Stay	3 days Interval 1.0 to 21.0	3 days Interval 1.0 to 16.0	2 days Interval 1.0 to 15.0

SECONDARY outcome

Timeframe: From Fontan operation until final chest tube removed, assessed during postoperative hospitalization, up to 90 days.

Days during which one or more chest tubes were in place following the Fontan operation.

Outcome measures

Measure	I- Nesiritide n=35 Participants Patients assigned to the nesiritide group will receive an intravenous loading dose of 2 mcg/kg followed by an infusion of 0.015 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. nesiritide: Nesiritide bolus 2 mcg/kg on CPB, then infusion of 0.015 mcg/kg/min. infusion dose may be adjusted	II- Milrinone n=36 Participants Patients assigned to the milrinone group will receive a bolus of 50 mcg/kg followed by an infusion of 0.5 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. milrinone: Milrinone 50 mcg/kg bolus on CPB, the infusion of 0.5 mcg/kg/min. Infusion rate may be adjusted	III- Placebo n=35 Participants Patients assigned to the placebo group will receive a 0.33 mL/kg bolus of 5% dextrose in water (D5W), followed by an infusion of D5W, administered for at least 12 hours after CICU admission and up to five days, unless prespecified lack of efficacy criteria are met. placebo: Placebo bolus on CPB, then placebo infusion
Resource Utilization: Chest Tube Days	5 days Interval 1.0 to 19.0	5 days Interval 1.0 to 21.0	5 days Interval 1.0 to 11.0

SECONDARY outcome

Timeframe: 180 days

Days the patient was alive and out of hospital within the 180 days after Fontan surgery

Outcome measures

Measure	I- Nesiritide n=35 Participants Patients assigned to the nesiritide group will receive an intravenous loading dose of 2 mcg/kg followed by an infusion of 0.015 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. nesiritide: Nesiritide bolus 2 mcg/kg on CPB, then infusion of 0.015 mcg/kg/min. infusion dose may be adjusted	II- Milrinone n=36 Participants Patients assigned to the milrinone group will receive a bolus of 50 mcg/kg followed by an infusion of 0.5 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. milrinone: Milrinone 50 mcg/kg bolus on CPB, the infusion of 0.5 mcg/kg/min. Infusion rate may be adjusted	III- Placebo n=35 Participants Patients assigned to the placebo group will receive a 0.33 mL/kg bolus of 5% dextrose in water (D5W), followed by an infusion of D5W, administered for at least 12 hours after CICU admission and up to five days, unless prespecified lack of efficacy criteria are met. placebo: Placebo bolus on CPB, then placebo infusion
Resource Utilization: Days Alive and Out of Hospital Within 180 Days of Surgery	167 days Interval 0.0 to 174.0	168 days Interval 102.0 to 173.0	170 days Interval 30.0 to 173.0

SECONDARY outcome

Timeframe: Preoperative baseline to 24 hours after CICU admission

Plasma norepinephrine levels measured at preoperative baseline and postoperative CICU hour 1, 8, 24.

Outcome measures

Measure	I- Nesiritide n=14 Participants Patients assigned to the nesiritide group will receive an intravenous loading dose of 2 mcg/kg followed by an infusion of 0.015 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. nesiritide: Nesiritide bolus 2 mcg/kg on CPB, then infusion of 0.015 mcg/kg/min. infusion dose may be adjusted	II- Milrinone n=18 Participants Patients assigned to the milrinone group will receive a bolus of 50 mcg/kg followed by an infusion of 0.5 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. milrinone: Milrinone 50 mcg/kg bolus on CPB, the infusion of 0.5 mcg/kg/min. Infusion rate may be adjusted	III- Placebo n=15 Participants Patients assigned to the placebo group will receive a 0.33 mL/kg bolus of 5% dextrose in water (D5W), followed by an infusion of D5W, administered for at least 12 hours after CICU admission and up to five days, unless prespecified lack of efficacy criteria are met. placebo: Placebo bolus on CPB, then placebo infusion
Plasma Norepinephrine Levels. Preoperative baseline	0.2 ng/mL Interval 0.1 to 4.2	0.4 ng/mL Interval 0.1 to 5.1	0.5 ng/mL Interval 0.1 to 1.3
Plasma Norepinephrine Levels. 1 hour after CICU admit	2.0 ng/mL Interval 0.6 to 18.0	2.1 ng/mL Interval 0.3 to 30.5	2.9 ng/mL Interval 0.4 to 13.1
Plasma Norepinephrine Levels. 8 hours after CICU admit	2.3 ng/mL Interval 0.3 to 11.0	2.4 ng/mL Interval 0.2 to 13.7	1.3 ng/mL Interval 0.1 to 15.8
Plasma Norepinephrine Levels. 24 hours after CICU admit	1.3 ng/mL Interval 0.1 to 12.1	1.5 ng/mL Interval 0.2 to 14.5	1.3 ng/mL Interval 0.1 to 13.6

SECONDARY outcome

Timeframe: Preoperative baseline to 24 hours after CICU admission

Plasma epinephrine levels measured at preoperative baseline and postoperative CICU hour 1, 8, 24.

Outcome measures

Measure	I- Nesiritide n=14 Participants Patients assigned to the nesiritide group will receive an intravenous loading dose of 2 mcg/kg followed by an infusion of 0.015 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. nesiritide: Nesiritide bolus 2 mcg/kg on CPB, then infusion of 0.015 mcg/kg/min. infusion dose may be adjusted	II- Milrinone n=18 Participants Patients assigned to the milrinone group will receive a bolus of 50 mcg/kg followed by an infusion of 0.5 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. milrinone: Milrinone 50 mcg/kg bolus on CPB, the infusion of 0.5 mcg/kg/min. Infusion rate may be adjusted	III- Placebo n=15 Participants Patients assigned to the placebo group will receive a 0.33 mL/kg bolus of 5% dextrose in water (D5W), followed by an infusion of D5W, administered for at least 12 hours after CICU admission and up to five days, unless prespecified lack of efficacy criteria are met. placebo: Placebo bolus on CPB, then placebo infusion
Epinephrine Levels Preoperative baseline	0 ng/mL Interval 0.0 to 0.1	0 ng/mL Interval 0.0 to 1.6	0 ng/mL Interval 0.0 to 0.4
Epinephrine Levels 1 hour after CICU admit	1.2 ng/mL Interval 0.0 to 6.2	2.7 ng/mL Interval 0.0 to 14.7	2.1 ng/mL Interval 0.1 to 8.4
Epinephrine Levels 8 hours after CICU admit	0.5 ng/mL Interval 0.0 to 3.3	0.5 ng/mL Interval 0.0 to 6.9	1.0 ng/mL Interval 0.1 to 5.8
Epinephrine Levels 24 hours after CICU admit	0.2 ng/mL Interval 0.0 to 1.5	1.5 ng/mL Interval 0.2 to 14.5	1.3 ng/mL Interval 0.1 to 13.6

SECONDARY outcome

Timeframe: Preoperative baseline to 24 hours after CICU admission

N-terminal pro-brain natriuretic peptide levels measured at preoperative baseline and postoperative CICU hour 1, 8, 24.

Outcome measures

Measure	I- Nesiritide n=14 Participants Patients assigned to the nesiritide group will receive an intravenous loading dose of 2 mcg/kg followed by an infusion of 0.015 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. nesiritide: Nesiritide bolus 2 mcg/kg on CPB, then infusion of 0.015 mcg/kg/min. infusion dose may be adjusted	II- Milrinone n=18 Participants Patients assigned to the milrinone group will receive a bolus of 50 mcg/kg followed by an infusion of 0.5 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. milrinone: Milrinone 50 mcg/kg bolus on CPB, the infusion of 0.5 mcg/kg/min. Infusion rate may be adjusted	III- Placebo n=15 Participants Patients assigned to the placebo group will receive a 0.33 mL/kg bolus of 5% dextrose in water (D5W), followed by an infusion of D5W, administered for at least 12 hours after CICU admission and up to five days, unless prespecified lack of efficacy criteria are met. placebo: Placebo bolus on CPB, then placebo infusion
N-terminal Pro-brain Natriuretic Peptide Levels Preoperative baseline	77 fmol/mL Interval 25.0 to 742.0	77 fmol/mL Interval 40.0 to 154.0	88 fmol/mL Interval 33.0 to 275.0
N-terminal Pro-brain Natriuretic Peptide Levels 1 hour after CICU admit	81 fmol/mL Interval 15.0 to 383.0	61 fmol/mL Interval 27.0 to 142.0	77 fmol/mL Interval 27.0 to 417.0
N-terminal Pro-brain Natriuretic Peptide Levels 8 hours after CICU admit	91 fmol/mL Interval 59.0 to 331.0	71 fmol/mL Interval 36.0 to 268.0	88 fmol/mL Interval 49.0 to 600.0
N-terminal Pro-brain Natriuretic Peptide Levels 24 hours after CICU admit	142 fmol/mL Interval 61.0 to 412.0	136 fmol/mL Interval 44.0 to 518.0	109 fmol/mL Interval 67.0 to 570.0

Adverse Events

I- Nesiritide

Serious events: 0 serious events

Other events: 24 other events

Deaths: 1 deaths

II- Milrinone

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

III- Placebo

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	I- Nesiritide n=35 participants at risk Patients assigned to the nesiritide group will receive an intravenous loading dose of 2 mcg/kg followed by an infusion of 0.015 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. nesiritide: Nesiritide bolus 2 mcg/kg on CPB, then infusion of 0.015 mcg/kg/min. infusion dose may be adjusted	II- Milrinone n=36 participants at risk Patients assigned to the milrinone group will receive a bolus of 50 mcg/kg followed by an infusion of 0.5 mcg/kg/min, administered for at least 12 hours after CICU admission and up to five days unless prespecified lack of efficacy criteria are met. milrinone: Milrinone 50 mcg/kg bolus on CPB, the infusion of 0.5 mcg/kg/min. Infusion rate may be adjusted	III- Placebo n=35 participants at risk Patients assigned to the placebo group will receive a 0.33 mL/kg bolus of 5% dextrose in water (D5W), followed by an infusion of D5W, administered for at least 12 hours after CICU admission and up to five days, unless prespecified lack of efficacy criteria are met. placebo: Placebo bolus on CPB, then placebo infusion
Cardiac disorders Hypotension	68.6% 24/35	75.0% 27/36	68.6% 24/35
Renal and urinary disorders Acute renal insufficiency	5.7% 2/35	2.8% 1/36	8.6% 3/35

Additional Information

John M. Costello, M.D., M.P.H.

Ann & Robert H. Lurie Children's Hospital of Chicago

Phone: 312 227 1551

Email: jmcostello@luriechildrens.org

Results disclosure agreements

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