Brief Title
A Study Evaluating the Efficacy and Safety of IV L-Citrulline for the Prevention of Clinical Sequelae of Acute Lung Injury Induced by Cardiopulmonary Bypass in Pediatric Patients Undergoing Surgery for Congenital Heart Defects
Official Title
A Phase III Double-Blind, Randomized, Placebo Controlled, Multi Center Clinical Study to Evaluate the Efficacy and Safety of Intravenous L-Citrulline for the Prevention of Clinical Sequelae of Acute Lung Injury Induced by Cardiopulmonary Bypass in Pediatric Patients Undergoing Surgery for Congenital Heart Defects
Brief Summary
This is a randomized, double-blind, placebo controlled, multicenter study to compare the efficacy and safety of L-citrulline versus placebo in patients undergoing surgery for congenital heart defects. Eligible patients undergoing repair of a large unrestrictive ventricular septal defect (VSD), a partial or complete atrioventricular septal defect (AVSD), or an ostium primum atrial septal defect (primum ASD) will be eligible for enrollment.
Detailed Description
This is a randomized, double-blind, placebo controlled, multicenter study that will compare the efficacy and safety of L- citrulline versus placebo in patients undergoing surgery for congenital heart defects. Eligible patients undergoing repair of a large unrestrictive ventricular septal defect (VSD), a partial or complete atrioventricular septal defect (AVSD), or an ostium primum atrial septal defect (primum ASD) will be eligible for enrollment. Each enrolled patient will be randomized to receive either L citrulline or placebo throughout all administrations in the study. Patients will receive: 1. an L-citrulline bolus of 150 mg/kg or placebo at the initiation of cardiopulmonary bypass 2. the addition L-citrulline or placebo to maintain a steady state target concentration of approximately 100 μmol/L of L-Citrulline or placebo during cardiopulmonary bypass 3. an L-citrulline bolus of 10 mg/kg or placebo 30 minutes after decannulation from cardiopulmonary bypass, followed immediately by a 9 mg/kg/hour continuous L-citrulline infusion or placebo for up to 48 hours post-first dose. The infusion rate will be adjusted (up or down titration of drug infusion) to achieve a target steady state concentration of 100 µmol/L. The study drug or placebo infusion will be discontinued once invasive arterial blood pressure monitoring is discontinued or at 48 hours, whichever occurs first. Patients will be followed until Day 28 or discharge from the hospital, whichever occurs first. For patients discharged prior to Day 28, a final assessment via telephone will be conducted at Day 28.
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Post-operative need for mechanical ventilation
Secondary Outcome
Intubation
Condition
Ventricular Septal Defect
Intervention
L-citrulline
Study Arms / Comparison Groups
Active
Description: Patients will receive: an L-citrulline bolus of 150 mg/kg at the initiation of cardiopulmonary bypass the addition L-citrulline to maintain a steady state target concentration of approximately 100 μmol/L of L-citrulline during cardiopulmonary bypass an L-citrulline bolus of 10 mg/kg 30 minutes after decannulation from cardiopulmonary bypass, followed immediately by a 9 mg/kg/hour continuous L-citrulline infusion or placebo for up to 48 hours post-first dose. The infusion rate will be adjusted (up or down titration of drug infusion) to achieve a target steady state concentration of 100 μmol/L. Infusion will be discontinued once invasive arterial blood pressure monitoring is discontinued or at 48 hours, whichever occurs first.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
97
Start Date
June 29, 2022
Completion Date
August 10, 2023
Primary Completion Date
June 15, 2023
Eligibility Criteria
Inclusion Criteria: - Patients, parents, or legal guardian willing and able to sign informed consent - Male and female subjects aged ≤18 years of age (females of child-bearing potential willing to practice an acceptable form of birth control) - Patients undergoing cardiopulmonary bypass for repair of a large unrestrictive ventricular septal defect, an ostium primum/secundum atrial septal defect, or a partial or complete atrioventricular septal defect - Pre-operative echocardiogram confirming cardiovascular anatomy and defect to be repaired Exclusion Criteria: - Evidence of pulmonary artery or vein abnormalities that will not be addressed surgically. Specific abnormalities excluded include: - significant pulmonary artery narrowing not amenable to surgical correction - previous pulmonary artery stent placement - significant left sided AV valve regurgitation not amenable to surgical correction - pulmonary venous return abnormalities not amenable to surgical correction - pulmonary vein stenosis not amenable to surgical correction - Preoperative requirement for mechanical ventilation or IV inotrope support - Presence of fixed or idiopathic pulmonary hypertension (i.e. Eisenmenger's Syndrome) prior to surgical repair - Pre-operative use of medications to treat pulmonary hypertension - Pregnancy; Sexually active females of child-bearing potential must be willing to practice an acceptable method of birth control for the duration of study participation (e.g. oral contraceptive, hormonal implant, intra-uterine device) - Participation in another clinical trial within 30 days of Screening or while participating in the current study, including the 28 days of follow-up post study drug administration. - Any condition which, in the opinion of the investigator, might interfere with the study objectives
Gender
All
Ages
N/A - 18 Years
Accepts Healthy Volunteers
No
Contacts
Christopher Mastropietro, MD, FCCM, +1 410.736.3750, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT05253209
Organization ID
CIT-CPB-003-02
Responsible Party
Sponsor
Study Sponsor
Asklepion Pharmaceuticals, LLC
Study Sponsor
Christopher Mastropietro, MD, FCCM, Principal Investigator, Riley Hospital for Children at Indiana University Health
Verification Date
July 2022