Phase 2
N=65
Intravenous L-Citrulline Influence on the Need for Invasive Mechanical Ventilation for Acute Hypoxemic Respiratory Failure in Patients With COVID-19
Acute Hypoxemic Respiratory Failure
Bottom Line
View on ClinicalTrials.gov: NCT04570384 ↗Enrolled (actual)
65
Serious AEs
24.6%
Results posted
Feb 2023
Primary outcome: Primary: Time to Non-invasive/Invasive Mechanical Ventilation — 96.65; 70.49 Hours — p=0.782
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- L-Citrulline (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Asklepion Pharmaceuticals, LLC
- Primary completion
- Aug 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time to Non-invasive/Invasive Mechanical Ventilation |
96.65; 70.49 | 0.782 |
| PRIMARY Time to Non-invasive Mechanical Ventilation |
66.17; 105.70 | 0.360 |
| PRIMARY Time to Invasive Mechanical Ventilation |
290.01; 148.07 | 0.285 |
| PRIMARY Systolic Blood Pressure |
118.63; 130.19 | — |
| PRIMARY Diastolic Blood Pressure |
73.58; 79.74 | — |
| PRIMARY Mean Arterial Pressure |
87.58; 94.30 | — |
| SECONDARY Blood Levels of Arginine |
67.6; 67.88; 92.57; 71.51; 128.11; 75.7 | — |
| SECONDARY Blood Levels of Citrulline |
24.64; 18.08; 1094.41; 18.39; 997.61; 21.84 | — |
| SECONDARY Evaluate the Effect of Intravenous L-Citrulline Compared to Placebo as Measured by the Total Length of All Mechanical Ventilation |
270.91; 451.87 | 0.668 |
| SECONDARY Evaluate the Effect of IV L-Citrulline to Placebo for Hospital All Cause Mortality |
2; 5 | 0.232 |
| SECONDARY Percentage of Patients Admitted to Intensive Care |
12; 13 | 0.729 |
| SECONDARY Duration of Intensive Care Unit (ICU) Stay |
14.83; 17.31 | 0.706 |
| SECONDARY Duration of Hospitalisation |
10.61; 11.88 | 0.834 |
| SECONDARY Number of Patients Requiring Intubation |
14; 12; 12; 10; 4; 6 | — |
| SECONDARY Overall Duration of Mechanical Ventilation |
239.31; 222.08; 224.64; 219.27; 274.27; 538.28 | — |
Summary
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-CoV2) Illness. To evaluate safety and efficacy of a bolus loading dose and continuous intravenous infusion of L-Citrulline compared to placebo in patients hospitalized with COVID-19 infection (SARS-CoV-2).
Eligibility Criteria
Inclusion Criteria
- Age 18-65 years.
- Clinical evidence of COVID-19 (SARS-CoV2) infection, defined as a positive COVID-19 laboratory test plus evidence of an acute hypoxemic respiratory illness requiring oxygen.
- Admitted and transferred to floor without intubation.
Exclusion Criteria
- No consent/inability to obtain consent
- Patient, surrogate, or physician not committed to full support
- Malignant or other irreversible condition and estimated 28-day mortality ≥ 50%
- Moribund patient not expected to survive 48 hours (as defined by primary medical team) from start of study infusion
- End-stage Liver Disease as defined by Child-Pugh Score > 9
- Currently enrolled in, or participated in another study of an investigational compound within the last 30 days
- Pregnant female, or female who is breast feeding
- Allergy to L-citrulline or arginine or any citrulline- or arginine-containing product
- Patient not otherwise suitable for the study in the opinion of any of the investigators
- Requirement for intubation and invasive mechanical ventilation before study enrollment
Data sourced from ClinicalTrials.gov (NCT04570384). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.