Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05253209
Other study ID # CIT-CPB-003-02
Secondary ID
Status Recruiting
Phase Phase 3
First received
Last updated
Start date June 29, 2022
Est. completion date February 10, 2024

Study information

Verified date August 2023
Source Asklepion Pharmaceuticals, LLC
Contact Gurdyal Kalsi, MD, MFPM
Phone +1 410.736.3750
Email gurdyal.kalsi@asklepionpharm.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 97
Est. completion date February 10, 2024
Est. primary completion date December 31, 2023
Accepts healthy volunteers No
Gender All
Age group N/A to 18 Years
Eligibility 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

Study Design


Intervention

Drug:
L-citrulline
Intravenous L-citrulline given for up to 48 hours
Plasmalyte A
Intravenous Plasmalyte A given for up to 48 hours

Locations

Country Name City State
United States Children's Hospital of Colorado Aurora Colorado
United States Children's of Alabama Birmingham Alabama
United States Heart Center, Ann & Robert H. Lurie Children's Hospital of Chicago Chicago Illinois
United States Cincinnati Children's Hospital Medical Center Cincinnati Ohio
United States Nationwide Children's Hospital- The Heart Center Columbus Ohio
United States Duke University Medical Center Surgical Office of Clinical Research (SOCR) Durham North Carolina
United States Riley Hospital for Children at Indiana University Health Indianapolis Indiana
United States University of Wisconsin-Madison Madison Wisconsin
United States Cardinal Glennon Children's Hospital Saint Louis Missouri
United States Seattle Children's Research Institute Seattle Washington

Sponsors (1)

Lead Sponsor Collaborator
Asklepion Pharmaceuticals, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Intubation Length of time on intubation From separation from bypass until discontinuation of intubation or Day 28, whichever occurs first
Secondary Early extubation Frequency of extubation <12 hours after surgery From end of surgery until 12 hours post-surgery
Secondary Positive pressure ventilation Length of time on non-invasive mechanical ventilation Time in hours from separation from CPB until discontinuation of all non-invasive mechanical ventilation or Day 28, whichever occurs first
Secondary Duration of hospitalization Number of post-operative days until discharge from hospital From surgery until discharge from hospital or Day 28, whichever occurs first
Secondary Use of inotropes Duration of inotrope use (e.g., dopamine, dobutamine, milrinone, epinephrine, phenylephrine and/or norepinephrine). Measured from first use until discharge or Day 28, whichever occurs first
Secondary Use of vasodilators Duration of vasodilator use (e.g., nitroprusside, nitroglycerin, and nicardipine) Measured from first use until discharge or Day 28, whichever occurs first
Secondary Duration of chest tube placement Total post-operative time chest tube is used From the end of the surgery to the time the chest tube is removed or Day 28, whichever occurs first
Secondary Volume of chest tube drainage Total amount of chest tube drainage (mL) Duration of chest tube placement or Day 28, whichever occurs first
Secondary Hemodynamic improvement (heart rate) Changes in heart rate measurements. 1, 2, 4, 12, 24, and 48 hours post-dose
Secondary Hemodynamic improvement (systemic arterial blood pressure) Changes in systemic arterial systolic and diastolic blood pressure measurements. 1, 2, 4, 12, 24, and 48 hours post-dose
Secondary Hemodynamic improvement (oxygen saturation) Changes in oxygen saturation measurements. 1, 2, 4, 12, 24, and 48 hours post-dose
Secondary Hemodynamic improvement (central venous pressure) Changes in oxygen saturation measurements. 1, 2, 4, 12, 24, and 48 hours post-dose
Secondary Hemodynamic improvement (pulmonary arterial pressure) Changes in PAP measurements (when available). 1, 2, 4, 12, 24, and 48 hours post-dose
Secondary Arterial blood gasses (PaO2) Changes in PaO2 measurements Intra-operatively to Day 28
Secondary Arterial blood gasses (PaCO2) Changes in PaCO2 measurements Intra-operatively to Day 28
Secondary Arterial blood gasses (HCO3) Changes in HCO3 measurements Intra-operatively to Day 28
Secondary Arterial blood gasses (pH) Changes in pH measurements Intra-operatively to Day 28
Secondary Plasma levels of L-citrulline to assess PK-PD (exposure-response) relationship Measurement of plasma levels of L-citrulline Pre-surgery, 6, 12, 24 and 48 hours after first dose
Secondary Health Economics: mechanical ventilation Measured as cost per day and expressed as incremental cost per quality adjusted life year (QALY) gained Total over duration of hospitalization or to Day 28 whichever occurs first
Secondary Health Economics: duration of hospitalisation Measured as total cost of hospitalisation expressed as incremental cost per quality adjusted life year (QALY) gained Total over duration of hospitalization or to Day 28 whichever occurs first
Secondary Adverse events Incidence of adverse events and serious adverse events Pre-operatively until Day 28
Secondary Incidence of refractory hypotension Number of subjects with any refractory hypotension. Defined as a drop of >20% in mean arterial pressure for >30 minutes. From the end of surgery until 48 hours after first dose
Secondary Clinical laboratory values (Blood Hemoglobin and Total Bilirubin) Absolute values and the absolute and percentage changes from baseline. Intra-operatively, Days 1, 2 and 28
Secondary Clinical laboratory values (Blood Haematocrit) Absolute values and the absolute and percentage changes from baseline. Intra-operatively, Days 1, 2 and 28
Secondary Clinical laboratory values (Red Blood Cell Count) Absolute values and the absolute and percentage changes from baseline. Intra-operatively, Days 1, 2 and 28
Secondary Clinical laboratory values (White Blood Cell Count) Absolute values and the absolute and percentage changes from baseline. Intra-operatively, Days 1, 2 and 28
Secondary Clinical laboratory values (Blood Platelet Count) Absolute values and the absolute and percentage changes from baseline. Intra-operatively, Days 1, 2 and 28
Secondary Clinical laboratory values (Blood Sodium, Potassium, Calcium, Magnesium, Chloride) Absolute values and the absolute and percentage changes from baseline. Intra-operatively, Days 1, 2 and 28
Secondary Clinical laboratory values (Blood Urea Nitrogen and Creatinine) Absolute values and the absolute and percentage changes from baseline. Intra-operatively, Days 1, 2 and 28
Secondary Clinical laboratory values (Blood Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase) Absolute values and the absolute and percentage changes from baseline. Intra-operatively, Days 1, 2 and 28
Secondary Clinical laboratory values (Blood Lactate Dehydrogenase) Absolute values and the absolute and percentage changes from baseline. Intra-operatively, Days 1, 2 and 28
Secondary Clinical laboratory values (Blood Activated Clotting Time) Absolute values and the absolute and percentage changes from baseline. Intra-operatively, Days 1, 2 and 28
See also
  Status Clinical Trial Phase
Completed NCT03684161 - Cardiopulmonary Function in Adults Born With a Ventricular Septal Defect
Completed NCT01120964 - Intravenous L-Citrulline to Treat Children Undergoing Heart Bypass Surgery : Revised Protocol Phase 1/Phase 2
Completed NCT02914652 - The Cardiopulmonary Effect of Inhaled Beta-2-agonists on Adult Patients Born With Ventricular Septum Defects. Phase 4
Recruiting NCT05939713 - Cera™ VSD Occluder Post Market Clinical Follow-up
Recruiting NCT06298344 - The Role of Thiamine After Transcatheter Closure in Children With Left-to-Right Shunt Congenital Heart Disease Early Phase 1
Recruiting NCT05688670 - Regional Anesthesia Following Pediatric Cardiac Surgery Phase 4
Completed NCT02138435 - Longterm Outcome After Ventricular Septal Defect Closure N/A
Completed NCT00556361 - Use of Ketamine Prior to Cardiopulmonary Bypass in Children Phase 2
Completed NCT05200910 - The Effect of Transcatheter VSD Closure on Children's Appetite, Hormones and Growth
Recruiting NCT03127748 - Cardiac Function After Transcatheter VSD Closure N/A
Enrolling by invitation NCT06214182 - Immune Heterogeneity Before and After Cardiopulmonary Bypass in Children
Active, not recruiting NCT04667455 - Improving Care for Children With Congenital Heart Disease. N/A
Completed NCT04417712 - Lifetech KONAR MFO Post-Market Clinical Follow-Up Study
Completed NCT01313832 - The Effect of Remote Ischemic Preconditioning on the Ischemic Reperfusion Injury in Infants With Ventricular Septal Defect and Pulmonary Hypertension N/A
Active, not recruiting NCT04017975 - Optical Tissue Identification for Myocardial Architecture Phase 2
Completed NCT01915277 - A Phase I Study of Dexmedetomidine Bolus and Infusion in Corrective Infant Cardiac Surgery: Safety and Pharmacokinetics Phase 1
Recruiting NCT03941691 - A Trial to Evaluate the Safety and Efficacy of a Fully Degradable Ventricular Septal Defect (VSD) Closure N/A
Completed NCT04859036 - The Effect of Transcatheter Ventricular Septal Defect Closure on Heart Rate Variability Parameters