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

Last updated: September 13, 2024
Sponsor: Asklepion Pharmaceuticals, LLC
Overall Status: Terminated

Phase

3

Condition

Acute Respiratory Distress Syndrome (Ards)

Heart Defect

Lung Injury

Treatment

Plasmalyte A

L-citrulline

Clinical Study ID

NCT05253209
CIT-CPB-003-02
  • Ages < 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

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 potentialwilling to practice an acceptable form of birth control)

  • Patients undergoing cardiopulmonary bypass for repair of a large unrestrictiveventricular septal defect, an ostium primum/secundum atrial septal defect, or apartial or complete atrioventricular septal defect

  • Pre-operative echocardiogram confirming cardiovascular anatomy and defect to berepaired

Exclusion

Exclusion Criteria:

  • Evidence of pulmonary artery or vein abnormalities that will not be addressedsurgically. 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 surgicalcorrection

  • 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 topractice an acceptable method of birth control for the duration of studyparticipation (e.g. oral contraceptive, hormonal implant, intra-uterine device)

  • Participation in another clinical trial within 30 days of Screening or whileparticipating in the current study, including the 28 days of follow-up post studydrug administration.

  • Any condition which, in the opinion of the investigator, might interfere with thestudy objectives

Study Design

Total Participants: 64
Treatment Group(s): 2
Primary Treatment: Plasmalyte A
Phase: 3
Study Start date:
June 29, 2022
Estimated Completion Date:
May 10, 2024

Study 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.

Connect with a study center

  • Children's of Alabama

    Birmingham, Alabama 35233
    United States

    Site Not Available

  • Children's Hospital of Colorado

    Aurora, Colorado 80045
    United States

    Site Not Available

  • Heart Center, Ann & Robert H. Lurie Children's Hospital of Chicago

    Chicago, Illinois 60611-2605
    United States

    Site Not Available

  • Riley Hospital for Children at Indiana University Health

    Indianapolis, Indiana 46202
    United States

    Site Not Available

  • Cardinal Glennon Children's Hospital

    Saint Louis, Missouri 63104
    United States

    Site Not Available

  • Duke University Medical Center Surgical Office of Clinical Research (SOCR)

    Durham, North Carolina 27710
    United States

    Site Not Available

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio 45229
    United States

    Site Not Available

  • Nationwide Children's Hospital- The Heart Center

    Columbus, Ohio 43215
    United States

    Site Not Available

  • Seattle Children's Research Institute

    Seattle, Washington 98105
    United States

    Site Not Available

  • University of Wisconsin-Madison

    Madison, Wisconsin 53792-4108
    United States

    Site Not Available

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