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

NCT05253209 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: CIT-CPB-003-02
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 10

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.

Conditions

Ventricular Septal Defect; Atrioventricular Septal Defect; Primum Atrial Septal Defect

Outcome Measures

Primary Outcomes (1)

• Post-operative need for mechanical ventilation

  Mechanical ventilation is defined as invasive and non-invasive mechanical ventilation including bilevel positive airway pressure (BPAP), continuous positive airway pressure (CPAP)

  Time in hours from separation from CPB until discontinuation of all mechanical ventilation including non-invasive support or Day 28, whichever occurs first

Secondary Outcomes (32)

• Intubation

  From separation from bypass until discontinuation of intubation or Day 28, whichever occurs first

• Early extubation

  From end of surgery until 12 hours post-surgery

• Positive pressure ventilation

  Time in hours from separation from CPB until discontinuation of all non-invasive mechanical ventilation or Day 28, whichever occurs first

• Duration of hospitalization

  From surgery until discharge from hospital or Day 28, whichever occurs first

• Use of inotropes

  Measured from first use until discharge or Day 28, whichever occurs first

Study Arms (2)

Active

EXPERIMENTAL

Patients will receive: 1. an L-citrulline bolus of 150 mg/kg at the initiation of cardiopulmonary bypass 2. the addition L-citrulline to maintain a steady state target concentration of approximately 100 μmol/L of L-citrulline during cardiopulmonary bypass 3. 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.

Drug: L-citrulline

Placebo

PLACEBO COMPARATOR

Plasmalyte A administered to the same schedule as the active treatment arm.

Drug: Plasmalyte A

Interventions

L-citrulline DRUG

Intravenous L-citrulline given for up to 48 hours

Active

Plasmalyte A DRUG

Intravenous Plasmalyte A given for up to 48 hours

Placebo

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Asklepion Pharmaceuticals, LLC: lead

Study Sites (10)

Children's of Alabama

Birmingham, Alabama, 35233, United States

Location

Children's Hospital of Colorado

Aurora, Colorado, 80045, United States

Location

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

Chicago, Illinois, 60611-2605, United States

Location

Riley Hospital for Children at Indiana University Health

Indianapolis, Indiana, 46202, United States

Location

Cardinal Glennon Children's Hospital

St Louis, Missouri, 63104, United States

Location

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

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Nationwide Children's Hospital- The Heart Center

Columbus, Ohio, 43215, United States

Location

Seattle Children's Research Institute

Seattle, Washington, 98105, United States

Location

University of Wisconsin-Madison

Madison, Wisconsin, 53792-4108, United States

Location

MeSH Terms

Conditions

Heart Septal Defects, Ventricular; Atrioventricular Septal Defect; Partial atrioventricular canal

Interventions

Citrulline; Plasmalyte A

Condition Hierarchy (Ancestors)

Heart Septal Defects; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Amino Acids, Diamino; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Christopher Mastropietro, MD, FCCM

  Riley Hospital for Children at Indiana University Health

  PRINCIPAL INVESTIGATOR

• Gurdyal Kalsi, MD, MFPM

  Asklepion Pharmaceuticals, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Randomization via an IWRS. Study drug or placebo will be prepared and labeled with the appropriate subject identifiers only; no information that would reveal the contents of the dose to be administered (active versus placebo) will be included on the label. Study drug (citrulline or placebo) will be provided in either identical syringes or bags and mask labeled. The bags will be the same size, shape, and fluid clarity, and hence masked to both investigators and staff administering the drug. Only the pharmacist and the unblinded monitor responsible for performing drug accountability (a different monitor than the person performing routine data monitoring) will be aware of the treatment assignment.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2022
• First Posted: February 23, 2022
• Study Start: June 29, 2022
• Primary Completion: May 10, 2024
• Study Completion: May 10, 2024
• Last Updated: September 19, 2024

Record last verified: 2023-08

Locations

US (10)