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

Effectiveness of a pharmacist-delivered smoking cessation program in the State of Qatar: a randomized controlled trial

Abstract Background Cigarette smoking is one of the major preventable causes of death and diseases in Qatar. The study objective was to test the effect of a structured smoking cessation program delivered by trained pharmacists on smoking cessation rates in Qatar. Methods A prospective randomized controlled trial was conducted in eight ambulatory pharmacies in Qatar. Eligible participants were smokers 18 years and older who smoked one or more cigarettes daily for 7 days, were motivated to quit, able to communicate in Arabic or English, and attend the program sessions. Intervention group participants met with the pharmacists four times at 2 to 4 week intervals. Participants in the control group received unstructured brief smoking cessation counseling. The primary study outcome was self-reported continuous abstinence at 12 months. Analysis was made utilizing data from only those who responded and also using intent-to-treat principle. A multinomial logistic regression model was fitted to assess the predictors of smoking at 12 months. Analysis was conducted using IBM-SPSS® version 23 and STATA® version 12. Results A total of 314 smokers were randomized into two groups: intervention (n = 167) and control (n = 147). Smoking cessation rates were higher in the intervention group at 12 months; however this difference was not statistically significant (23.9% vs. 16.9% p = 0.257). Similar results were observed but with smaller differences in the intent to treat analysis (12.6% vs. 9.5%, p = 0.391). Nevertheless, the daily number of cigarettes smoked for those who relapsed was significantly lower (by 4.7 and 5.6 cigarettes at 3 and 6 months respectively) in the intervention group as compared to the control group (p = 0.041 and p = 0.018 respectively). At 12 months, the difference was 3.2 cigarettes in favor of the intervention group but was not statistically significant (p = 0.246). Years of smoking and daily number of cigarettes were the only predictors of smoking as opposed to quitting at 12 months (p = 0.005; p = 0.027 respectively). Conclusions There was no statistically significant difference in the smoking cessation rate at 12 months between the groups. However, the smoking cessation program led to higher (albeit non-significant) smoking cessation rates compared with usual care. More research should be conducted to identify factors that might improve abstinence. Trial registration Clinical Trials NCT02123329 . Registration date 20 April 201