Intravenous L-Citrulline Influence on the Need for Invasive Mechanical Ventilation for Acute Hypoxemic Respiratory Failure in Patients With COVID-19

NCT04570384 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CIT-COVID19-002-01
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Acute Hypoxemic Respiratory Failure

Outcome Measures

Primary Outcomes (6)

• Time to Non-invasive/Invasive Mechanical Ventilation

  Time in hours from the initiation of the treatment until mechanical ventilation is required, whether non-invasive (e.g., high flow nasal cannula, bilevel positive airway pressure, oxygen therapy) or invasive (i.e., requiring intubation).

  From the start of infusion to Day 60 Follow-up

• Time to Non-invasive Mechanical Ventilation

  Time in hours from the initiation of the treatment until non-invasive mechanical ventilation is required (e.g., high flow nasal cannula, bilevel positive airway pressure, oxygen therapy) .

  From the start of infusion to Day 60 Follow-up

• Time to Invasive Mechanical Ventilation

  Time in hours from the initiation of the treatment until intubation for invasive mechanical ventilation is required.

  From the start of infusion to Day 60 Follow-up

• Systolic Blood Pressure

  Systolic blood pressure measured in mmHg

  Day 1

• Diastolic Blood Pressure

  Diastolic blood pressure measured in mmHg

  Day 1

• Mean Arterial Pressure

  Mean arterial pressure measured in mmHg

  Day 1

Secondary Outcomes (9)

• Blood Levels of Arginine

  Plasma levels of arginine at 0, 2 and 12 hours, and 2, 4, 6, 8, 10 days after initiation of treatment

• Blood Levels of Citrulline

  Plasma levels of citrulline at 0, 2 and 12 hours, and 2, 4, 6, 8, 10 days after initiation of treatment

• Evaluate the Effect of Intravenous L-Citrulline Compared to Placebo as Measured by the Total Length of All Mechanical Ventilation

  Day 1 through Day 60 Follow Up

• Evaluate the Effect of IV L-Citrulline to Placebo for Hospital All Cause Mortality

  Day 1 through day 12

• Percentage of Patients Admitted to Intensive Care

  Day 1 through Day 12 (DC)

Study Arms (2)

IV L-Citrulline (Turnobi) Arm

ACTIVE COMPARATOR

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.

Drug: L-Citrulline

Placebo Arm

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

L-Citrulline DRUG

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.

Also known as: L-CIT, CIT

IV L-Citrulline (Turnobi) Arm

Placebo DRUG

Patients randomized to placebo will receive equal volume bolus and study infusion of 5% dextrose water for a maximum of 10 days.

Placebo Arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Asklepion Pharmaceuticals, LLC: lead

Study Sites (1)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

MeSH Terms

Conditions

Respiratory Insufficiency

Interventions

Citrulline; serum P-component

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Diamino; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

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

gurdyal.kalsi@asklepionpharm.com

+1 410.736.3750

Study Officials

• Gurdyal Kalsi, MD, MFPM

  Asklepion Pharmaceuticals, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double Blind Clinical Trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Placebo controlled and Active Drug

Study Record Dates

• First Submitted: September 17, 2020
• First Posted: September 30, 2020
• Study Start: October 15, 2020
• Primary Completion: August 30, 2021
• Study Completion: September 30, 2021
• Last Updated: February 22, 2023
• Results First Posted: February 22, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)