Intravenous L-Citrulline to Treat Children Undergoing Heart Bypass Surgery : Revised Protocol

NCT01120964 | Completed Phase 1 Results DMC

• 1 other identifier: CIT-002-01
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief 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). 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. The objective of this study is to determine in a randomized placebo controlled phase IB multicenter clinical trial if a revised protocol of intravenous L-citrulline delivery given perioperatively achieves a plasma citrulline level of \> 100 umol/L in children undergoing surgical repair of an atrial septal defect,ventricular septal defect or an atrioventricular septal defect.

Conditions

Atrial Septal Defect; Ventricular Septal Defect; Atrioventricular Septal Defect

Outcome Measures

Primary Outcomes (1)

• L-citrulline Plasma Levels

  Citrulline Blood Levels: 1. Baseline sample in OR prior to Cardiopulmonary Bypass prior to administration of first bolus of Citrulline or Placebo 2. Immediately after Bolus 1 administered in Operating Room. 3. 30 minutes after separation from Cardiopulmonary Bypass; immediately prior to administration of Bolus 2 and start of continuous infusion of Citrulline or Placebo. 4. Six hours after after start of infusion. 5. 12 hours after start of infusion. 6. 24 hours after start of infusion. 7. 48 hours after start of infusion; or whenever infusion is discontinued if prior to 48 hours.

  Measured in seven blood sample time points from the beginning of surgery until end of IV Citrulline Infusion; at either 48 hours postoperatively or at extubation, whichever comes first.

Secondary Outcomes (15)

• Postoperative Invasive Mechanical Ventilation (Mean and SD)

  Measured in hours from the end of surgery until extubation, or Day 30, whichever occurs first

• Postoperative Invasive Mechanical Ventilation (Median and Range)

  Measured in hours from the end of surgery until extubation or Day 30, whichever occurred first

• Total Duration of Respiratory Support

  Baseline to discharge or Day 30, whichever occurs first

• Postoperative Intravenous Inotrope Duration

  Measured at 48 hours

• Total Inotrope Score

  PICU admission until Hour 48

Other Outcomes (2)

• Arginine Concentrations

  Baseline to Hour 48

• Nitric Oxide Concentrations

  Baseline to Hour 48

Study Arms (2)

Intravenous L-Citrulline

EXPERIMENTAL

IV bolus of 150 mg/kg L-citrulline at the initiation of bypass, followed by L-citrulline (200 μmol/L) addition to the filtration or hemoconcentration replacement fluid used during bypass. Plus L-citrulline (20 mg/kg) bolus 30 minutes after decannulation from bypass, immediately followed by 9 mg/kg/h continuous L-citrulline infusion for 48 hours.

Drug: Intravenous L-Citrulline

Placebo of Intravenous L-Citrulline

PLACEBO COMPARATOR

Placebo administered according to the same schedule as L-citrulline

Drug: Placebo of Intravenous L-Citrulline

Interventions

Intravenous L-Citrulline DRUG

Intravenous L-Citrulline

Placebo of Intravenous L-Citrulline DRUG

Placebo of intravenous L-Citrulline given at the same prescribed times as L-Citrullne Drug

Placebo of Intravenous L-Citrulline

Eligibility Criteria

• Age: Up to 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Informed Consent signed by the subject's legal representative
• Subjects \< 6 years old
• Subjects undergoing cardiopulmonary bypass for repair of an atrial septal defect, a ventricular septal defect or an atrioventricular septal defect

You may not qualify if:

• Pulmonary artery or vein abnormalities being addressed surgically
• Preoperative requirement for invasive mechanical ventilation or intravenous inotrope support
• Any condition which, in the opinion of the investigator, might interfere with study objectives

Sponsors & Collaborators

• Asklepion Pharmaceuticals, LLC: lead

Study Sites (2)

Washington University Children's Hospital

St Louis, Missouri, 63110, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Heart Septal Defects, Atrial; Heart Septal Defects, Ventricular; Atrioventricular Septal Defect

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Gurdyal Kalsi, MD, MFPM (Hon)
• Organization: Asklepion Pharmaceuticals, LLC

gurdyal.kalsi@asklepionpharm.com

+1 410.736.3750

Study Officials

• Frederick E Barr, MD

  Batson Children's Hospital, University of Mississippi Medical Center

  STUDY CHAIR

• Catherine Krawczeski, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

• Allan Doctor, MD

  St. Louis Children's Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2010
• First Posted: May 11, 2010
• Study Start: September 1, 2010
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: July 27, 2022
• Results First Posted: June 21, 2022

Record last verified: 2022-07

Locations

US (2)