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

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 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

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