A Phase 3 interventional study of L-citrulline and Plasmalyte A in Ventricular Septal Defect, Atrioventricular Septal Defect and Primum Atrial Septal Defect, sponsored by Asklepion Pharmaceuticals, LLC. Terminated at 10 sites in United States. Open to participants aged Up to 18 Years. Per ClinicalTrials.gov, last updated 2024-09-19.
Sponsored by Asklepion Pharmaceuticals, LLC · Phase 3, Interventional, and Prevention
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.
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:
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.
399 studies on the registry are indexed under Lung Injury; 50 are open to participants now.
This study's enrollment of 64 is above the median of 53 across 239 interventional studies indexed under Lung Injury.
Browse Lung Injury studies →Asklepion Pharmaceuticals, LLC is the lead sponsor of 6 studies on the registry; 1 is open to participants now.
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Exclusion Criteria:
Evidence of pulmonary artery or vein abnormalities that will not be addressed surgically. Specific abnormalities excluded include:
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
Plasmalyte A administered to the same schedule as the active treatment arm.
Drug: Plasmalyte A
Intravenous L-citrulline given for up to 48 hours
Intravenous Plasmalyte A given for up to 48 hours
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 frame: Time in hours from separation from CPB until discontinuation of all mechanical ventilation including non-invasive support or Day 28, whichever occurs first
Intubation
Length of time on intubation
Time frame: From separation from bypass until discontinuation of intubation or Day 28, whichever occurs first
Early extubation
Frequency of extubation \<12 hours after surgery
Time frame: From end of surgery until 12 hours post-surgery
Positive pressure ventilation
Length of time on non-invasive mechanical ventilation
Time frame: Time in hours from separation from CPB until discontinuation of all non-invasive mechanical ventilation or Day 28, whichever occurs first
Duration of hospitalization
Number of post-operative days until discharge from hospital
Time frame: From surgery until discharge from hospital or Day 28, whichever occurs first
Use of inotropes
Duration of inotrope use (e.g., dopamine, dobutamine, milrinone, epinephrine, phenylephrine and/or norepinephrine).
Time frame: Measured from first use until discharge or Day 28, whichever occurs first
Use of vasodilators
Duration of vasodilator use (e.g., nitroprusside, nitroglycerin, and nicardipine)
Time frame: Measured from first use until discharge or Day 28, whichever occurs first
Duration of chest tube placement
Total post-operative time chest tube is used
Time frame: From the end of the surgery to the time the chest tube is removed or Day 28, whichever occurs first
Volume of chest tube drainage
Total amount of chest tube drainage (mL)
Time frame: Duration of chest tube placement or Day 28, whichever occurs first
Hemodynamic improvement (heart rate)
Changes in heart rate measurements.
Time frame: 1, 2, 4, 12, 24, and 48 hours post-dose
Hemodynamic improvement (systemic arterial blood pressure)
Changes in systemic arterial systolic and diastolic blood pressure measurements.
Time frame: 1, 2, 4, 12, 24, and 48 hours post-dose
Hemodynamic improvement (oxygen saturation)
Changes in oxygen saturation measurements.
Time frame: 1, 2, 4, 12, 24, and 48 hours post-dose
Hemodynamic improvement (central venous pressure)
Changes in oxygen saturation measurements.
Time frame: 1, 2, 4, 12, 24, and 48 hours post-dose
Hemodynamic improvement (pulmonary arterial pressure)
Changes in PAP measurements (when available).
Time frame: 1, 2, 4, 12, 24, and 48 hours post-dose
Arterial blood gasses (PaO2)
Changes in PaO2 measurements
Time frame: Intra-operatively to Day 28
Arterial blood gasses (PaCO2)
Changes in PaCO2 measurements
Time frame: Intra-operatively to Day 28
Arterial blood gasses (HCO3)
Changes in HCO3 measurements
Time frame: Intra-operatively to Day 28
Arterial blood gasses (pH)
Changes in pH measurements
Time frame: Intra-operatively to Day 28
Plasma levels of L-citrulline to assess PK-PD (exposure-response) relationship
Measurement of plasma levels of L-citrulline
Time frame: Pre-surgery, 6, 12, 24 and 48 hours after first dose
Health Economics: mechanical ventilation
Measured as cost per day and expressed as incremental cost per quality adjusted life year (QALY) gained
Time frame: Total over duration of hospitalization or to Day 28 whichever occurs first
Health Economics: duration of hospitalisation
Measured as total cost of hospitalisation expressed as incremental cost per quality adjusted life year (QALY) gained
Time frame: Total over duration of hospitalization or to Day 28 whichever occurs first
Adverse events
Incidence of adverse events and serious adverse events
Time frame: Pre-operatively until Day 28
Incidence of refractory hypotension
Number of subjects with any refractory hypotension. Defined as a drop of \>20% in mean arterial pressure for \>30 minutes.
Time frame: From the end of surgery until 48 hours after first dose
Clinical laboratory values (Blood Hemoglobin and Total Bilirubin)
Absolute values and the absolute and percentage changes from baseline.
Time frame: Intra-operatively, Days 1, 2 and 28
Clinical laboratory values (Blood Haematocrit)
Absolute values and the absolute and percentage changes from baseline.
Time frame: Intra-operatively, Days 1, 2 and 28
Clinical laboratory values (Red Blood Cell Count)
Absolute values and the absolute and percentage changes from baseline.
Time frame: Intra-operatively, Days 1, 2 and 28
Clinical laboratory values (White Blood Cell Count)
Absolute values and the absolute and percentage changes from baseline.
Time frame: Intra-operatively, Days 1, 2 and 28
Clinical laboratory values (Blood Platelet Count)
Absolute values and the absolute and percentage changes from baseline.
Time frame: Intra-operatively, Days 1, 2 and 28
Clinical laboratory values (Blood Sodium, Potassium, Calcium, Magnesium, Chloride)
Absolute values and the absolute and percentage changes from baseline.
Time frame: Intra-operatively, Days 1, 2 and 28
Clinical laboratory values (Blood Urea Nitrogen and Creatinine)
Absolute values and the absolute and percentage changes from baseline.
Time frame: Intra-operatively, Days 1, 2 and 28
Clinical laboratory values (Blood Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase)
Absolute values and the absolute and percentage changes from baseline.
Time frame: Intra-operatively, Days 1, 2 and 28
Clinical laboratory values (Blood Lactate Dehydrogenase)
Absolute values and the absolute and percentage changes from baseline.
Time frame: Intra-operatively, Days 1, 2 and 28
Clinical laboratory values (Blood Activated Clotting Time)
Absolute values and the absolute and percentage changes from baseline.
Time frame: Intra-operatively, Days 1, 2 and 28
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