Heart Defects, CongenitalPhase 1/2NCT00281671
Nesiritide Use Following Cardiac Surgery in Infants
A Phase 1/2 study testing nesiritide in people with Heart Defects, Congenital and Cardiopulmonary Bypass, run by Boston Children's Hospital at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages Up to 1 year
- Conditions the study is for
- Heart Defects, Congenital, Cardiopulmonary Bypass
- What is being tested?
- nesiritide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Apr 2006to Oct 2008
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 1 year
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- > 48 hours after cardiac surgery requiring cardiopulmonary bypass
- < 1 year of age
- Receiving chlorothiazide and furosemide for > 12 hours
- Urine output < 4 cc/kg/hour, or fluid intake > output for 2 consecutive days
- Receiving mechanical ventilation
- Presence of body wall edema on CXR, defined as a radiologic index of > 2
- Plan for > 24 hrs further diuresis before chest closure or extubation
Who cannot join
- Age > 365 days at the time of enrollment
- Corrected estimated gestational age < 35 weeks at the time of enrollment
- Serum creatinine > 2.0 mg/dL at the time of enrollment
- Significant hemodynamic instability at the time of enrollment
- Lack of dedicated intravenous access for nesiritide infusion
- Lack of arterial line for continuous blood pressure monitoring
- Lack of a Foley catheter for continuous urine collection
- Enrollment in another research study such that the outcomes of either study may be confounded by participation in this study, or such that the amount of blood drawn for research purposes becomes excessive.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital Boston
Boston, Massachusetts, 02115
About this study
Official title: Pilot Study of the Effects of Nesiritide on Hemodynamics and Urine Output Following Cardiopulmonary Bypass in Infants
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.
Read the detailed description
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.
- Conditions
- Heart Defects, Congenital, Cardiopulmonary Bypass
- Being tested
- nesiritide, Placebo
- Keywords
- Nesiritide, Natriuretic Peptide, Brain, Heart Defects, Congenital, Cardiopulmonary Bypass, Diuretics
- Medical subject headings
- Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nesiritideDrug
Also called Natrecor
nesiritide 0.015 mcg/kg/hour x 10 hours
PlaceboDrug
Also called 0.9% sodium chloride infusion
0.9% sodium chloride infusion
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Placebo |
| 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. Receives: Drug: nesiritide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Urine Output
Urine output measured in cc/kg/hour during the last 5 hours of the study drug infusion
Measured: 5 hours
Secondary outcomes (3)
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.
Measured: 48 hours
Urine Output
Measured: 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.
Measured: Baseline (hour 0) and 6 hours after onset of study drug infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2006 (estimated)
- Study start8 Apr 2006
- Primary completionOct 2008
- Study completionOct 2008
Why it stopped: Slow patient enrollment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Heart Defects, CongenitalStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, John M Costello, Boston Children's Hospital
- Investigators
- John M Costello, MD, Principal investigator, Department of Cardiology, Children's Hospital Boston
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00281671
- Sponsor's protocol ID
- 05-12-160
- Status last verified
- May 2018
- First submitted
- 23 Jan 2006
- Last updated
- 27 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided: Email PI for data requests.
Publications
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.
PubMed 16153935Costello 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.
PubMed 14735254Mahle 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.
PubMed 16148814Simsic 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.
PubMed 14994182
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of the Effects of Nesiritide on Hemodynamics and Urine Output Following Cardiopulmonary Bypass in Infants
- ClinicalTrials.gov ID
- NCT00281671
- Acronym / sponsor ID
- 05-12-160
- Conditions
- Heart Defects, Congenital, Cardiopulmonary Bypass
- Keywords
- Nesiritide, Natriuretic Peptide, Brain, Heart Defects, Congenital, Cardiopulmonary Bypass, Diuretics
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow patient enrollment.
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Study start
- 8 Apr 2006
- Primary completion
- Oct 2008 (actual)
- Study completion
- Oct 2008 (actual)
- First posted
- 25 Jan 2006 (estimated)
- Results
- Posted 27 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboIn 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 | Drug: nesiritideIn 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. |
Who may qualify
- Ages
- Up to 1 year
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- > 48 hours after cardiac surgery requiring cardiopulmonary bypass
- < 1 year of age
- Receiving chlorothiazide and furosemide for > 12 hours
- Urine output < 4 cc/kg/hour, or fluid intake > output for 2 consecutive days
- Receiving mechanical ventilation
Key exclusion criteria (8 listed)
- Age > 365 days at the time of enrollment
- Corrected estimated gestational age < 35 weeks at the time of enrollment
- Serum creatinine > 2.0 mg/dL at the time of enrollment
- Significant hemodynamic instability at the time of enrollment
- Lack of dedicated intravenous access for nesiritide infusion
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| nesiritideAlso: Natrecornesiritide 0.015 mcg/kg/hour x 10 hours | Drug | Nesiritide |
| PlaceboAlso: 0.9% sodium chloride infusion0.9% sodium chloride infusion | Drug | Placebo |
Primary outcome
Urine Output
Time frame: 5 hours
Urine output measured in cc/kg/hour during the last 5 hours of the study drug infusion
3 secondary outcomes
Number of Participants With Hypotension and Bradycardia
Time frame: 48 hours
Urine Output
Time frame: 10 hours
Cardiac Index
Time frame: Baseline (hour 0) and 6 hours after onset of study drug infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16153935Costello 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.
- Background: PubMed 14735254Costello 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.
- Background: PubMed 16148814Mahle 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.
- Background: PubMed 14994182Simsic 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.
- Individual participant dataSharing planned: Undecided. Email PI for data requests.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John M Costello, MD principal investigator
Department of Cardiology, Children's Hospital Boston
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing nesiritide in people with Heart Defects, Congenital and Cardiopulmonary Bypass, run by Boston Children's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Urine Output (time frame: 5 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00281671, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2020; AzTrials last refreshed its copy on 6 Nov 2026.