Supplemental Citicoline Administration to Reduce Lung Injury Efficacy Trial (SCARLET)

NCT05881135 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 2022H0451
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this single center, double-blinded, placebo-controlled, and randomized Phase 1 trial is to determine if i.v. citicoline is safe and efficacious compared to i.v. saline/control in adults presenting with SARS CoV-2 infection complicated by acute hypoxemic respiratory failure. The main questions it aims to answer:

• Is citicoline safe in this patient population?
• Does citicoline have a benefit in terms of improving oxygenation?
• Does citicoline reduce overall severity of illness as reflected by standardized scales. Patients will be assigned to i.v. treatment with citicoline or saline twice daily for 5 consecutive days. SpO2/FiO2 ratios will be recorded daily as per standard clinical practice to compare citicoline treatments at three different doses to placebo.

Conditions

COVID-19

Outcome Measures

Primary Outcomes (2)

• Safety of citicoline over a range of doses in COVID-19 patients presenting with acute hypoxemic respiratory failure.

  Safety will be assessed in each arm of the study: 1, 5, or 10 mg/kg/day citicoline by i.v. bolus or i.v. saline bolus for 5 consecutive days. Safety analysis will be performed based on a continuous safety monitoring rule to guide accrual suspension decisions based on number of treatment-related adverse events as assessed by the CTCAE v.5.0. The number of patients with an SAE that would warrant temporary suspension of accrual in a given group corresponds to a high posterior probability that the true SAE probability is greater than an acceptable level (i.e., Pr(pi \> 0.25 \| data) \> 0.85), where the posterior probability is determined from a Beta-Binomial distribution with Beta (1, 1) as the prior on pi.

  Until hospital discharge or up to 29 days

• Citicoline's effect on acute hypoxemic respiratory failure in COVID-19 patients.

  The primary clinical outcome will be measured on Day 3: lowest recorded SpO2/FiO2 ratio.

  Day 3

Secondary Outcomes (2)

• Effect of citicoline on COVID specific disease severity scale in patients with acute COVID associated hypoxemic respiratory failure.

  Through day 8

• Effect of citicoline on Sequential Organ Failure Score (SOFA) in patients with COVID associated acute respiratory failure.

  Through day 8

Study Arms (4)

IV 1 mg/kg/day Citicoline

EXPERIMENTAL

i.v. bolus of 10 ml normal saline containing citicoline 1 mg/kg, administered twice daily for 5 days.

Drug: Citicoline

IV 5 mg/kg/day Citicoline

EXPERIMENTAL

i.v. bolus of 10 ml normal saline containing 5 mg/kg citicoline, administered twice daily for 5 days.

Drug: Citicoline

IV 10 mg/kg/day Citicoline

EXPERIMENTAL

i.v. bolus of 10 ml normal saline containing 10 mg/kg citicoline, administered twice daily for 5 days.

Drug: Citicoline

IV 10 ml normal saline

PLACEBO COMPARATOR

i.v. bolus of 10 ml normal saline (without active ingredient) administered i.v., twice daily for 5 days.

Drug: Saline/Placebo

Interventions

Citicoline DRUG

i.v. bolus administration every 12 hours for 5 days.

Also known as: Somazina, CDP-choline

IV 1 mg/kg/day Citicoline; IV 10 mg/kg/day Citicoline; IV 5 mg/kg/day Citicoline

Saline/Placebo DRUG

i.v. administered every 12 hours as a 10 ml bolus for 5 days.

Also known as: Normal saline solution

IV 10 ml normal saline

Eligibility Criteria

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

You may not qualify if:

• Subjects who are unable or unwilling to give written informed consent or to comply with study protocol and who have no legal authorized representative available to give consent on their behalf
• Individuals being treated with extracorporeal membrane oxygenation (ECMO)
• Subjects who, in the clinicians estimation, will be unlikely to survive the protocol duration due to imminent and unavoidable risk of death
• Individuals with hypertonia of the parasympathetic nervous system
• Prisoners
• Children (\<18 years)
• Women who may be pregnant, are pregnant, or have plans to become pregnant
• Women who are breast feeding
• Individuals with a known allergy to citicoline
• Subjects that are taking medications that contain L-Dopa, centrophenoxine, or meclofenoxate
• Subjects with past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the principal investigator (PI), may pose additional risks from participation in the study or that may impact the quality or interpretation of the data obtained from the study.

Sponsors & Collaborators

• Ohio State University: lead

Study Sites (1)

The Ohio State Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Pannu S, Exline MC, Bednash JS, Englert JA, Diaz P, Bartlett A, Brock G, Wu Q, Davis IC, Crouser ED. SCARLET (Supplemental Citicoline Administration to Reduce Lung injury Efficacy Trial): study protocol for a single-site, double-blinded, placebo-controlled, and randomized Phase 1/2 trial of i.v. citicoline (CDP-choline) in hospitalized SARS CoV-2-infected patients with hypoxemic acute respiratory failure. Trials. 2024 May 18;25(1):328. doi: 10.1186/s13063-024-08155-0.

  PMID: 38760804 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

Cytidine Diphosphate Choline; Sodium Chloride; Saline Solution

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Choline; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Cytidine Diphosphate; Cytosine Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Internal Medicine

Study Record Dates

• First Submitted: April 25, 2023
• First Posted: May 31, 2023
• Study Start: June 6, 2023
• Primary Completion: March 17, 2025
• Study Completion: April 1, 2026
• Last Updated: April 2, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)