Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The effects of interferon alpha-2b in combination with ribavirin on health related quality of life and work productivity

BACKGROUND/AIMS: Interferon plus ribavirin is the most effective therapy for chronic hepatitis C. The aim of this study was to evaluate the effect of chronic hepatitis C and therapy on health-related quality of life and work functioning. METHODS: Nine hundred and twelve patients with hepatitis C infection were randomized in a controlled trial of Interferon alpha 2b 3 MU tiw for 24 or 48 weeks plus ribavirin 1000-1200 mg or placebo. Questionnaire-based assessments of health-related quality of life and work functioning were performed before, during, and after treatment. Outcome measures included the SF-36 Health Survey and additional generic and specific scales. Work functioning was assessed as missed days, shorter hours or less productivity at work. RESULTS: Pre-treatment, patients had significant impairment in five of eight SF-36 concepts compared to matched population norms. Sustained responders had a return to normal for four of these five concepts. Quality of life did not improve in non-responders. Improvements in histology, viral load or ALT values predicted improvements in quality of life. Sustained responders also had improvements in work functioning and productivity. CONCLUSIONS: Hepatitis C patients had impaired quality of life. After combination therapy, sustained virologic responders achieved benefits in their quality of life and work functioning

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

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