Abstract Introduction Acute hypoxemic respiratory failure (AHRF) is a common sequela of pulmonary infections and can progress to acute respiratory distress syndrome (ARDS). Effective AHRF/ARDS therapeutics are lacking. We sought to determine if addition of citicoline, a precursor of phospholipid synthesis, to standard of care (SoC) safely attenuates AHRF and systemic inflammatory responses in hospitalized COVID-19 patients. Methods This was a single-site, double-blinded, placebo-controlled, and block-randomized inpatient clinical trial (ClinicalTrials.gov: NCT05881135) conducted at the Ohio State University Medical Center. Adult subjects with AHRF (on ≥ 2 L/min supplemental O2 and SpO2 ≤ 94%), positive for SARS CoV-2 within 10 days prior to randomization, and with plasma C-reactive protein 10 mg/L were enrolled and randomly assigned by the investigational pharmacy to SoC + 0.5, 2.5, or 5 mg/kg citicoline or sterile normal saline, i.v., every 12 hours for 5 days. The primary outcome was a statistically significant increase in lowest recorded SpO2:FiO2 (S:F) ratios between day of enrollment (Study Day 1) and Day 3, at P 0.05. Results Nine (6M/3F) SoC + placebo and 24 (12M/12F) SoC + citicoline subjects were enrolled. No test agent-attributable adverse or serious adverse events were observed. Unlike placebo, addition of citicoline to SoC (including dexamethasone, remdesivir) significantly increased lowest SpO2:FiO2 ratios relative to Day 1 on Days 2, 3, 4, 5, and 8 (Figure). There was no significant dose-effect. Hence, the citicoline treatment data was pooled for analysis. Relative to Day 1, citicoline also significantly reduced composite and respiratory SOFA scores, plasma C-reactive protein, and plasma RAGE by Day 3. There was no impact on other organs based on SOFA criteria. Conclusions i.v. citicoline rapidly and safely improves oxygenation and systemic inflammatory responses beyond SoC in patients with SARS CoV-2-associated AHRF/ARDS. Larger trials are needed to definitively show clinical benefit for citicoline in this population or patients with AHRF/ARDS from other causes. Funding sources: U01-AI167784 (EDC, ICD), UM1-TR004548 (ICD) This abstract is funded by: NIH
Crouser et al. (Fri,) studied this question.