Journal Article

Impact of the COVID‐19 Pandemic on Conduct and Results of CLEAR Outcomes Trial

Nissen, Steven E., Nicholls, Stephen J., Sasiela, William J., Laffin, Luke J., Robinson, Paula, Li, Na, Bloedon, LeAnne, Mason, Denise, Singh, Abhayjit, Sarraju, Ashish, Michael Lincoff, A., Kelly, Stephanie

2024

Overview

Introduction The COVID‐19 pandemic disrupted clinical research. CLEAR Outcomes investigated the effect of bempedoic acid (BA) versus placebo in 13 970 patients with statin intolerance and high cardiovascular (CV) risk. BA reduced the risk of the primary endpoint (composite of CV death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization) by 13%. CLEAR Outcomes began before and continued for 2.7 years after the start of the pandemic. Methods The impact of the COVID‐19 pandemic on patient disposition, adverse events, and major adverse CV events (MACE) in CLEAR Outcomes was assessed. Results Rates of severe infection, hospitalization, or first MACE associated with a positive COVID‐19 test were low and balanced between treatment groups. Rates of all‐cause death, non‐CV death, and undetermined death increased in the pandemic period compared with the pre‐pandemic period, while rates of CV death with a known etiology remained stable. A sensitivity analysis excluding undetermined deaths occurring after the onset of the pandemic from the CV death designation yielded hazard ratios of 0.84 (95% CI, 0.76–0.93) for the primary endpoint and 0.94 (95% CI, 0.76–1.16) for the secondary endpoint of CV death, compared with 0.87 (95% CI, 0.79–0.96) and 1.04 (95% CI, 0.88–1.24), respectively, in the original analysis. Conclusion The CLEAR Outcomes trial continued uninterrupted throughout the COVID‐19 pandemic. Certain trial endpoints may have been impacted by the pandemic. Specifically, the classification of undetermined deaths as CV deaths may have attenuated the effect of BA on key efficacy endpoints. The CLEAR Outcomes trial was conducted uninterrupted during the COVID‐19 pandemic due to key changes in study procedures. The definitions of the trial endpoints were not altered for the pandemic, raising the possibility that outcomes related to cardiovascular mortality may have been impacted.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Acids / Aged / bempedoic acid / Cardiovascular Diseases - epidemiology / Cardiovascular Diseases - mortality / cardiovascular outcomes / clinical trial / Clinical Trial Result / Clinical trials / Coronaviruses / COVID-19 / COVID-19 - epidemiology / Disease transmission / Drug withdrawal / Female / Heart attacks / Humans / Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use / hyperlipidemia / Infections / Male / Middle Aged / Pandemics / Patients / Randomized Controlled Trials as Topic / SARS-CoV-2 / statin intolerance / Treatment Outcome