Efficacy and Safety of Pacritinib vs Placebo for Patients With Severe COVID-19: A Phase 2 Randomized Clinical Trial.
JAMA Netw Open
; 5(12): e2242918, 2022 Dec 01.
Article
in English
| MEDLINE | ID: covidwho-2148219
ABSTRACT
Importance The morbidity and mortality associated with COVID-19 remain high despite advances in standard of care therapy, and the role of anti-inflammatory agents that inhibit the interleukin 6/JAK2 pathway is still being elucidated. Objective:
To evaluate the efficacy and safety of the oral JAK2/IRAK1 inhibitor pacritinib vs placebo in the treatment of adults with severe COVID-19. Design, Setting, andParticipants:
This phase 2, double-blind, placebo-controlled, randomized clinical trial enrolled hospitalized adult patients with severe COVID-19 at 21 centers across the US between June 2020 and February 2021, with approximately 1.5 months of safety follow-up per patient. Data analysis was performed from September 2021 to July 2022.Interventions:
Patients were randomized 11 to standard of care plus pacritinib (400 mg per os on day 1 followed by 200 mg twice daily on days 2-14) vs placebo, for 14 days. Main Outcomes andMeasures:
The primary end point was death or need for invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) by day 28. All-cause mortality and safety were also assessed.Results:
A total of 200 patients were randomized to pacritinib (99 patients; 56 men [56.6%]; median [range] age, 60 [19-87] years) or placebo (101 patients; 64 men [63.4%]; median [range] age 59 [28-94] years). The percentage requiring supplementary oxygen was 99.0% (98 patients) in the pacritinib group vs 98.0% (99 patients) in the placebo group. The percentage who progressed to IMV, ECMO, or death was 17.2% (17 patients) in the pacritinib group vs 22.8% (23 patients) in the placebo group (odds ratio, 0.62; 95% CI, 0.28-1.35; P = .23). Among patients with elevated interleukin 6, the rate was 17.5% (11 of 63 patients) in the pacritinib group vs 30.4% (21 of 96 patients) in the placebo group. The adverse event rate was similar for pacritinib vs placebo (78.1% [75 patients] vs 80.2% [81 patients]), with no excess in infection (14.6% [14 patients] vs 19.8% [20 patients]), bleeding (8.3% [8 patients] vs 10.9% [11 patients]), or thrombosis (8.3% [8 patients] vs 7.9% [8 patients]). Rates of grade 3 or higher adverse events were lower with pacritinib than placebo (29.2% [28 patients] vs 40.6% [41 patients]). Conclusions and Relevance The study did not meet its primary end point in patients with severe COVID-19. Subgroup analyses may indicate specific populations with hyperinflammation that could benefit from pacritinib, although further clinical trials would be needed to confirm these effects. Trial Registration ClinicalTrials.gov Identifier NCT04404361.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
COVID-19 Drug Treatment
Type of study:
Cohort study
/
Experimental Studies
/
Prognostic study
/
Randomized controlled trials
Topics:
Variants
Limits:
Adult
/
Humans
/
Male
/
Middle aged
Language:
English
Journal:
JAMA Netw Open
Year:
2022
Document Type:
Article
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