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

Outcomes of a randomized controlled trial of a clinical pharmacy intervention in 52 nursing homes

AIMS: To evaluate whether a year long clinical pharmacy program involving development of professional relationships, nurse education on medication issues, and individualized medication reviews could change drug use, mortality and morbidity in nursing home residents. METHODS: A cluster randomised controlled trial, where an intervention home was matched to three control homes, was used to examine the effect of the clinical pharmacy intervention on resident outcomes. The study involved 905 residents in 13 intervention nursing homes and 2325 residents in 39 control nursing homes in south-east Queensland and north-east New South Wales, Australia. The outcome measures were: continuous drug use data from government prescription subsidy claims, cross-sectional drug use data on prescribed and administered medications, deaths and morbidity indices (hospitalization rates, adverse events and disability indices). RESULTS: This intervention resulted in a reduction in drug use with no change in morbidity indices or survival. Differences in nursing home characteristics, as defined by cluster analysis with SUDAAN, negated intervention-related apparent significant improvements in survival. The use of benzodiazepines, nonsteroidal anti-inflammatory drugs, laxatives, histamine H2-receptor antagonists and antacids was significantly reduced in the intervention group, whereas the use of digoxin and diuretics remained similar to controls. Overall, drug use in the intervention group was reduced by 14.8% relative to the controls, equivalent to an annual prescription saving of A64 dollars per resident (approximately 25 pound sterling). CONCLUSIONS: This intervention improved nursing home resident outcomes related to changes in drug use and drug-related expenditure. The continuing divergence in both drug use and survival at the end of the study suggests that the difference would have been more significant in a larger and longer study, and even more so using additional instruments specific for measuring outcomes related to changes in drug use