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Slow patient enrollment.
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The purpose of this study is to determine the effects of nesiritide on urine output and hemodynamics following cardiopulmonary bypass in infants. Safety and pharmacokinetic data will also be obtained.
Nesiritide, a recombinant human B-type natriuretic peptide, has vasodilatory, lusitropic and diuretic properties in healthy humans, and improves hemodynamics and symptoms in adults with decompensated congestive heart failure. Several retrospective case series suggest that nesiritide has beneficial effects on hemodynamics and urine output in adults and children following cardiac surgery.
The purpose of this prospective, randomized, double-blind, crossover study is to evaluate the effects of a continuous infusion of nesiritide on postoperative hemodynamics and urine output in infants with congenital heart disease who undergo cardiac surgery requiring cardiopulmonary bypass (CPB). Patients less than 1 year of age following cardiac surgery will be eligible for the study if they have received two conventional diuretics (furosemide and chlorothiazide) for at least 12 hours, yet are not effectively achieving a negative fluid balance, thus prohibiting sternal closure or tracheal extubation. Patients will be randomized to receive either a 10-hour infusion of nesiritide, a two hour washout period, followed by a 10-hour infusion of placebo, or this study drug sequence in reverse order. During the 24-hour study period, serial cardiac output measurements and BNP levels will be obtained, vital signs and intracardiac filling pressures will be recorded, and urine output will be measured.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | In this crossover pilot study, patients are randomly assigned to receive either nesiritide or placebo infusion for 10 hours, followed by a two hour washout period, and then the other study drug for 10 hours. |
|
| Nesiritide | Experimental | In this crossover pilot study, patients are randomly assigned to receive either nesiritide or placebo infusion for 10 hours, followed by a two hour washout period, and then the other study drug for 10 hours. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| nesiritide | Drug | nesiritide 0.015 mcg/kg/hour x 10 hours |
|
| Measure | Description | Time Frame |
|---|---|---|
| Urine Output | Urine output measured in cc/kg/hour during the last 5 hours of the study drug infusion | 5 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Hypotension and Bradycardia | Hypotension (mean arterial blood pressure < 40 mmHg for > 30 minutes) that is refractory to volume administration, increased inotropic/vasopressor support, and weaning of other vasodilators (e.g., milrinone) or sedatives Bradycardia, defined as 1) a decrease in heart rate of more than 30 beats/minute from baseline following the initiation of study drug infusion that 2) results in new requirement for temporary atrial pacing or other treatment specifically to increase heart rate and 3) is not readily explainable by other conditions. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| John M Costello, MD | Department of Cardiology, Children's Hospital Boston | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital Boston | Boston | Massachusetts | 02115 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16153935 | Background | Costello JM, Backer CL, Checchia PA, Mavroudis C, Seipelt RG, Goodman DM. Effect of cardiopulmonary bypass and surgical intervention on the natriuretic hormone system in children. J Thorac Cardiovasc Surg. 2005 Sep;130(3):822-9. doi: 10.1016/j.jtcvs.2005.03.008. | |
| 14735254 | Background | Costello JM, Backer CL, Checchia PA, Mavroudis C, Seipelt RG, Goodman DM. Alterations in the natriuretic hormone system related to cardiopulmonary bypass in infants with congestive heart failure. Pediatr Cardiol. 2004 Jul-Aug;25(4):347-53. doi: 10.1007/s00246-003-0512-5. |
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Email PI for data requests.
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Recruitment: April 2006- June 2007.
Location: Cardiac ICU in a large children's hospital.
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| ID | Title | Description |
|---|---|---|
| FG000 | Nesiritide First, Then Placebo | Patients assigned to this arm received nesiritide 0.015 mcg/kg/hour for 10 hours, followed by a two hour washout period, and then a placebo infusion (0.9 normal saline) for 10 hours |
| FG001 | Placebo First, Then Nesiritide | Patients assigned to this arm received a placebo infusion (0.9 normal saline) for 10 hours, followed by a two hour washout period, and then nesiritide 0.015 mcg/kg/hour for 10 hours |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | Because all participants were randomized to receive all interventions, baseline measurements are combined rather that reported by Arm/Group. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Urine Output | Urine output measured in cc/kg/hour during the last 5 hours of the study drug infusion | Posted | Median | Full Range | cc/kg/hr | 5 hours |
|
Initiation of study interventions until 48 hours after the study drug infusions ended.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Nesiritide | Patients received nesiritide 0.015 mcg/kg/hour for 10 hours | 0 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| John M. Costello, MD MPH | Ann & Robert H. Lurie Children's Hospital of Chicago | 312 227 1551 | jmcostello@luriechildrens.org |
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| ID | Term |
|---|---|
| D006330 | Heart Defects, Congenital |
| ID | Term |
|---|---|
| D018376 | Cardiovascular Abnormalities |
| D002318 | Cardiovascular Diseases |
| D006331 | Heart Diseases |
| D000013 | Congenital Abnormalities |
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| ID | Term |
|---|---|
| D020097 | Natriuretic Peptide, Brain |
| ID | Term |
|---|---|
| D045265 | Natriuretic Peptides |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
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| Placebo | Drug | 0.9% sodium chloride infusion |
|
|
| 48 hours |
| Urine Output | 10 hours |
| Cardiac Index | Cardiac index is based on the cardiac output, which is the amount of blood the left ventricle ejects into the systemic circulation in one minute, measured in liters per minute (l/min). Cardiac output is indexed to a patient's body size by dividing by the body surface area (m^2) to yield the cardiac index. Cardiac index was calculated in patients with an SVC catheter (previously placed for clinical indications) using the Fick principle using measured oxygen consumption (VO2), hemoglobin levels, and the difference between arterial and superior vena cava oxygen saturation. Oxygen consumption was measured using a real-time gas exchange technique with the Deltatrack II gas sensor. | Baseline (hour 0) and 6 hours after onset of study drug infusion |
| 16148814 | Background | Mahle WT, Cuadrado AR, Kirshbom PM, Kanter KR, Simsic JM. Nesiritide in infants and children with congestive heart failure. Pediatr Crit Care Med. 2005 Sep;6(5):543-6. doi: 10.1097/01.pcc.0000164634.58297.9a. |
| 14994182 | Background | Simsic JM, Reddy VS, Kanter KR, Kirshbom PM, Forbess JM. Use of nesiritide (human B-type natriuretic peptide) in infants following cardiac surgery. Pediatr Cardiol. 2004 Nov-Dec;25(6):668-70. doi: 10.1007/s00246-003-0680-3. |
| days |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Northeast United States | Number | participants |
|
| Weight | Median | Full Range | Kg |
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| Prematurity | Count of Participants | Participants |
|
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| Secondary | Number of Participants With Hypotension and Bradycardia | Hypotension (mean arterial blood pressure < 40 mmHg for > 30 minutes) that is refractory to volume administration, increased inotropic/vasopressor support, and weaning of other vasodilators (e.g., milrinone) or sedatives Bradycardia, defined as 1) a decrease in heart rate of more than 30 beats/minute from baseline following the initiation of study drug infusion that 2) results in new requirement for temporary atrial pacing or other treatment specifically to increase heart rate and 3) is not readily explainable by other conditions. | Posted | Count of Participants | Participants | 48 hours |
|
|
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| Secondary | Urine Output | Posted | Median | Full Range | cc/kg/hr | 10 hours |
|
|
|
| Secondary | Cardiac Index | Cardiac index is based on the cardiac output, which is the amount of blood the left ventricle ejects into the systemic circulation in one minute, measured in liters per minute (l/min). Cardiac output is indexed to a patient's body size by dividing by the body surface area (m^2) to yield the cardiac index. Cardiac index was calculated in patients with an SVC catheter (previously placed for clinical indications) using the Fick principle using measured oxygen consumption (VO2), hemoglobin levels, and the difference between arterial and superior vena cava oxygen saturation. Oxygen consumption was measured using a real-time gas exchange technique with the Deltatrack II gas sensor. | Cardiac index was only able to be measured for 4 of the 9 subjects enrolled in the trial. | Posted | Median | Full Range | L/min/m^2 | Baseline (hour 0) and 6 hours after onset of study drug infusion |
|
|
|
| 9 |
| 0 |
| 9 |
| 0 |
| 9 |
| EG001 | Placebo | Patients assigned to this arm received a placebo infusion (0.9 normal saline) for 10 hours | 0 | 9 | 0 | 9 | 0 | 9 |
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| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |