Intravenous L-Citrulline to Delay and Potentially Prevent the Need for Invasive Mechanical Ventilation for Acute Hypoxemic Respiratory Failure in Patients With COVID-19 (SARS-CoV-2) Illness
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|ClinicalTrials.gov Identifier: NCT04570384|
Recruitment Status : Recruiting
First Posted : September 30, 2020
Last Update Posted : September 9, 2021
|Condition or disease||Intervention/treatment||Phase|
|Acute Hypoxemic Respiratory Failure||Drug: L-Citrulline Drug: Placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||66 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Placebo controlled and Active Drug|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Double Blind Clinical Trial|
|Official Title:||Prospective, Randomized, Double-Blind, Placebo-Controlled Phase II Trial of Intravenous L-Citrulline (Turnobi) to Delay and Potentially Prevent the Need for Invasive Mechanical Ventilation for Acute Hypoxemic Respiratory Failure in Patients With COVID-19 (SARS-CoV-2) Illness|
|Actual Study Start Date :||October 15, 2020|
|Actual Primary Completion Date :||August 30, 2021|
|Estimated Study Completion Date :||October 30, 2021|
Active Comparator: IV L-Citrulline (Turnobi) Arm
Patients randomized to citrulline will receive an initial intravenous bolus of 20 mg/kg (to a maximum of 1500 mg) L-citrulline over 10 minutes. The study solution will be prepared as a 5% isotonic solution (50 mg/mL) in 5% dextrose water. Immediately after the initial bolus, a continuous intravenous infusion of L-citrulline at 9 mg/kg (max 700 mg) per hour will be administered through a dedicated intravenous line or port of a multi-lumen catheter.
L-Citrulline (Turnobi) for Injection. Patients will receive an initial bolus of 20 mg/kg (maximum 1500 mg), followed by study infusion of 9 mg/kg per hour (maximum 700mg) for up to 10 days.
Other Name: L-CIT, CIT
Placebo Comparator: Placebo Arm
Patients randomized to placebo arm will receive an infusion of 5% dextrose water matched for volume and color to the citrulline infusion. The placebo infusion will consist of an initial iv bolus (up to 30 mL) over 10 minutes followed by a continuous infusion of 5% dextrose water (about 15 mL/hr). The initial bolus and subsequent infusion will be administered through a dedicated intravenous line or port of a multi-lumen catheter.
Patients randomized to placebo will receive equal volume bolus and study infusion of 5% dextrose water for a maximum of 10 days.
- Primary Biochemical Objective to measure levels of citrulline and arginine in the Blood [ Time Frame: Day 1 through Day 60 Follow up ]The primary biochemical objective of this trial is to evaluate the effects of intravenous L-Citrulline on plasma levels of citrulline and arginine in patients admitted to the hospital with COVID-19 infection (SARS-CoV2) and acute hypoxemic respiratory symptoms requiring oxygen therapy. An association of plasma amino acid levels to clinical outcomes may serve as surrogate marker for response. Also measured is time on vent and time in ICU along with hospital stay
- The primary safety objective is a beneficial effect of intravenous L-Citrulline on hemodynamic status. [ Time Frame: Day 1 through Day 10 ]Hemodynamic measurements will be converted to a vasopressor dependency index (VDI) for analysis through day 10
- Primary Clinical Objective [ Time Frame: Day 1 through day 60 Follow-up ]The primary clinical objective is to evaluate the difference in the length of time to an intubation event in hours from the start of study infusion between the study arms.
- Evaluate the Safety of L-Citrulline [ Time Frame: Day 1 through Day 60 Follow-up ]To evaluate the safety of intravenous L-Citrulline compared to placebo as measured by incidence of reported adverse events.
- Evaluate the effect of intravenous L-Citrulline compared to placebo as measured by the total length of all mechanical ventilation [ Time Frame: Dat 1 through Day 12 ]To evaluate the effect of intravenous L-Citrulline compared to placebo as measured by the total length of all mechanical ventilation, including non-invasive modalities such as high flow nasal cannula and BiPAP and oxygen therapy.
- Evaluate the Effect of IV L-Citrulline to Placebo for Hospital all cause mortality [ Time Frame: Day 1 through day 12 ]To evaluate the effect of intravenous L-Citrulline compared to placebo on Hospital all-cause mortality
- Evaluate the Effect of IV L-Citrulline to Placebo on length of ICU and Hospital Stay [ Time Frame: Day 1 through Day 12 (DC) ]To evaluate the effect of intravenous L-Citrulline compared to placebo on lengths of ICU and hospital stay
- Evaluate overall difference in intubation rates [ Time Frame: Day 1 to Day 10 ]To evaluate overall difference in intubation rates
- Evaluate overall duration of mechanical ventilation from consent and post-infusion [ Time Frame: Day 1 through day 10 ]To evaluate overall duration of mechanical ventilation from consent and post-infusion
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04570384
|Contact: Gurdyal Kalsi, MD, MFPMfirstname.lastname@example.org|
|Contact: Vincent Elliottemail@example.com|
|United States, Arkansas|
|University of Arkansas for Medical Sciences||Recruiting|
|Little Rock, Arkansas, United States, 72205|
|Contact: Study Site Contact 501-398-8622 TRIcoordinators@uams.edu|
|Principal Investigator: Nikhil K Meena, MD|
|Sub-Investigator: Michael P Wilson, MD|
|Study Director:||Gurdyal Kalsi, MD, MFPM||Asklepion Pharmaceuticals, LLC|