Heart Defects, CongenitalPhase 3NCT00335244
Intravenous L-Citrulline to Treat Children Undergoing Heart Bypass Surgery
A Phase 3 study testing L-citrulline in people with Heart Defects, Congenital and Hypertension, Pulmonary, run by Asklepion Pharmaceuticals, LLC at 1 site in United States.
Trial summary
This clinical trial will determine the safety and effectiveness of intravenous L-citrulline in children undergoing cardiopulmonary bypass during heart surgery. Participants will be randomly assigned to either L-citrulline or a placebo (a substance that has no medicine in it). Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Heart Defects, Congenital, Hypertension, Pulmonary
- What is being tested?
- L-citrulline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 77 participants
- Where
- 1 siteUnited States
- Study dates
- May 2006to Dec 2009
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Undergoing cardiopulmonary bypass surgery with 1 of the following 5 procedures:
- AVSD repair
- VSD repair
- Bidirectional Glenn
- Modified Fontan
- Arterial switch
Who cannot join
- Pulmonary artery or vein abnormalities not being addressed surgically
- Preoperative requirement for mechanical ventilation or intravenous inotrope support
- Any condition that might interfere with study objectives, as determined by the investigator
- Pregnant
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
Official title: A Phase III Single-Blind, Randomized, Placebo Controlled, Clinical Trial to Determine the Safety and Efficacy of Intravenous L-Citrulline Versus Placebo in Children Undergoing Cardiopulmonary Bypass
This clinical trial will determine the safety and effectiveness of intravenous L-citrulline in children undergoing cardiopulmonary bypass during heart surgery. Participants will be randomly assigned to either L-citrulline or a placebo (a substance that has no medicine in it).
Citrulline is a protein building block in the body that can convert into another substance, nitric oxide (NO), which controls blood pressure in the lungs. Increased blood pressure in the lungs can be an important surgical problem; it may also lead to problems following surgery, such as severe high blood pressure in the lungs (pulmonary hypertension), increased time spent on a breathing machine, and a longer stay in the intensive care unit (ICU). The hypothesis of this study is that perioperative supplementation with intravenous citrulline will increase plasma citrulline, arginine and NO metabolites and prevent elevations in the postoperative PVT leading to a decrease in the duration of postoperative invasive mechanical ventilation.
Read the detailed description
Increased pulmonary vascular tone (PVT) can complicate the postoperative course of the following five surgical procedures for congenital heart defects: 1) unrestrictive ventricular septal defect (VSD) repair; 2) atrioventricular septal (AVSD) repair; 3) arterial switch procedure for transposition of the great arteries (TGA); 4) bidirectional Glenn shunt procedure; and 5) Fontan procedure for single ventricle lesions. PVT is partially controlled by NO. Arginine, the precursor to NO, is a product of the urea cycle. Preliminary data have been presented regarding 169 infants and children who have undergone one of six previous surgical procedures. It was found that urea cycle function and plasma arginine levels were significantly decreased in all participants. Furthermore, participants with increased PVT had significantly lower arginine levels compared to participants with normal PVT. Finally, a genetic single nucleotide polymorphism (SNP) in the rate limiting urea cycle enzyme (carbamyl phosphate synthetase I [CPSl T1405N]) appeared to affect postoperative plasma arginine levels and PVT. The hypothesis is that genetic polymorphisms in the rate limiting urea cycle enzyme CPSl, and other important enzymes in the urea cycle, influence the availability of NO precursors. It is further hypothesized that perioperative enhancement of urea cycle function with the key urea cycle intermediate (citrulline) will increase plasma arginine and NO metabolites and prevent elevations in PVT.
- Conditions
- Heart Defects, Congenital, Hypertension, Pulmonary
- Being tested
- L-citrulline, Placebo of intravenous L-citrulline
- Medical subject headings
- Heart Defects, Congenital, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-citrullineDrug
150mg bolus X 1 after initiation of cardiopulmonary bypass followed by continuous infusion of 9mg/kg/hr IV, starting 4 hours post bolus administration and ending at 48 hours continuous infusion or discharge from the PCCU
Placebo of intravenous L-citrullineDrug
Placebo of intravenous L-citrulline
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Intravenous L-citrulline Receives: Drug: L-citrulline |
| 2 | Placebo comparator | Placebo of intravenous L-citrulline Receives: Drug: Placebo of intravenous L-citrulline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Duration of postoperative mechanical ventilation in hours compared between treatment groups.
Measured: Measured in hours from the end of surgery until extubation
Secondary outcomes (6)
Incidence of increased PVT (defined as a sustained mean pulmonary artery pressure greater than 20 mm Hg for at least 2 hours, measured during the first 48 hours
Measured: Measured in hours from the end of surgery until extubation
Postoperative intravenous inotrope score
Measured: Measured at 48 hours
Length and volume of chest tube drainage
Measured: Measured in hours from the end of surgery until removal of chest tubes
Length of ICU stay
Measured: Measured in hours from the end of surgery to discharge from ICU
Length of hospitalization
Measured: Measured from the day of surgery until discharge from hospital
Survival
Measured: Measured at 30 days post surgical repair
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2006 (estimated)
- Study startMay 2006
- Primary completionDec 2009
- Study completionDec 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Defects, CongenitalStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- Asklepion Pharmaceuticals, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Vanderbilt University
- Responsible party
- Sponsor
- Investigators
- Fredrick E. Barr, MD, MSCI, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00335244
- Sponsor's protocol ID
- 409
- Other IDs
- R01HL073317-01, IRB# 060197
- Status last verified
- Jan 2015
- First submitted
- 7 Jun 2006
- Last updated
- 2 Feb 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Single-Blind, Randomized, Placebo Controlled, Clinical Trial to Determine the Safety and Efficacy of Intravenous L-Citrulline Versus Placebo in Children Undergoing Cardiopulmonary Bypass
- ClinicalTrials.gov ID
- NCT00335244
- Acronym / sponsor ID
- 409
- Conditions
- Heart Defects, Congenital, Hypertension, Pulmonary
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 77 participants (actual)
- Lead sponsor
- Asklepion Pharmaceuticals, LLCIndustry (pharma, biotech, devices)
- Collaborators
- Vanderbilt University
- Study start
- May 2006
- Primary completion
- Dec 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 9 Jun 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical trial will determine the safety and effectiveness of intravenous L-citrulline in children undergoing cardiopulmonary bypass during heart surgery. Participants will be randomly assigned to either L-citrulline or a placebo (a substance that has no medicine in it).
Citrulline is a protein building block in the body that can convert into another substance, nitric oxide (NO), which controls blood pressure in the lungs. Increased blood pressure in the lungs can be an important surgical problem; it may also lead to problems following surgery, such as severe high blood pressure in the lungs (pulmonary hypertension), increased time spent on a breathing machine, and a longer stay in the intensive care unit (ICU). The hypothesis of this study is that perioperative supplementation with intravenous citrulline will increase plasma citrulline, arginine and NO metabolites and prevent elevations in the postoperative PVT leading to a decrease in the duration of postoperative invasive mechanical ventilation.
Detailed description
Increased pulmonary vascular tone (PVT) can complicate the postoperative course of the following five surgical procedures for congenital heart defects: 1) unrestrictive ventricular septal defect (VSD) repair; 2) atrioventricular septal (AVSD) repair; 3) arterial switch procedure for transposition of the great arteries (TGA); 4) bidirectional Glenn shunt procedure; and 5) Fontan procedure for single ventricle lesions. PVT is partially controlled by NO. Arginine, the precursor to NO, is a product of the urea cycle. Preliminary data have been presented regarding 169 infants and children who have undergone one of six previous surgical procedures. It was found that urea cycle function and plasma arginine levels were significantly decreased in all participants. Furthermore, participants with increased PVT had significantly lower arginine levels compared to participants with normal PVT. Finally, a genetic single nucleotide polymorphism (SNP) in the rate limiting urea cycle enzyme (carbamyl phosphate synthetase I [CPSl T1405N]) appeared to affect postoperative plasma arginine levels and PVT. The hypothesis is that genetic polymorphisms in the rate limiting urea cycle enzyme CPSl, and other important enzymes in the urea cycle, influence the availability of NO precursors. It is further hypothesized that perioperative enhancement of urea cycle function with the key urea cycle intermediate (citrulline) will increase plasma arginine and NO metabolites and prevent elevations in PVT.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: L-citrullineIntravenous L-citrulline |
| 2 | Placebo comparator | Drug: Placebo of intravenous L-citrullinePlacebo of intravenous L-citrulline |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Undergoing cardiopulmonary bypass surgery with 1 of the following 5 procedures:
Key exclusion criteria (4 listed)
- Pulmonary artery or vein abnormalities not being addressed surgically
- Preoperative requirement for mechanical ventilation or intravenous inotrope support
- Any condition that might interfere with study objectives, as determined by the investigator
- Pregnant
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 |
|---|---|---|
| L-citrulline150mg bolus X 1 after initiation of cardiopulmonary bypass followed by continuous infusion of 9mg/kg/hr IV, starting 4 hours post bolus administration and ending at 48 hours continuous infusion or discharge from the PCCU | Drug | 1 |
| Placebo of intravenous L-citrullinePlacebo of intravenous L-citrulline | Drug | 2 |
Primary outcome
Duration of postoperative mechanical ventilation in hours compared between treatment groups.
Time frame: Measured in hours from the end of surgery until extubation
6 secondary outcomes
Incidence of increased PVT (defined as a sustained mean pulmonary artery pressure greater than 20 mm Hg for at least 2 hours, measured during the first 48 hours
Time frame: Measured in hours from the end of surgery until extubation
Postoperative intravenous inotrope score
Time frame: Measured at 48 hours
Length and volume of chest tube drainage
Time frame: Measured in hours from the end of surgery until removal of chest tubes
Length of ICU stay
Time frame: Measured in hours from the end of surgery to discharge from ICU
Length of hospitalization
Time frame: Measured from the day of surgery until discharge from hospital
Survival
Time frame: Measured at 30 days post surgical repair
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2015.
Related trials for Heart Defects, Congenital
Not yet recruiting
Autologous Thymus Transplant in Children With Congenital Heart Disease: A Pilot Study
Congenital Heart Disease (CHD)
RecruitingPhase 1
A Study of SGT-212 Gene Therapy in Friedreich's Ataxia
Friedreich's Ataxia (FA)
RecruitingObservational study
The CACHE Study: Coronary Artery Care in HaEmophilia
Haemophilia, Cardiovascular Diseases
RecruitingObservational study
Essen Amyloidosis Registry
Amyloidosis; Systemic, Amyloidosis Cardiac
Not yet recruitingObservational study
Early Nutrition and Heart Structure and Function in Preterm Infants During the First Year of Life
Cardiac Abnormalities, Nutrient Intake
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.
Fredrick E. Barr, MD, MSCI principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing L-citrulline in people with Heart Defects, Congenital and Hypertension, Pulmonary, run by Asklepion Pharmaceuticals, LLC 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 6 inclusion and 4 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: finished, as of the sponsor's last update on 2 Feb 2015. 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 phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Duration of postoperative mechanical ventilation in hours compared between treatment groups. (time frame: Measured in hours from the end of surgery until extubation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Feb 2015.