Ramipril for the Treatment of COVID-19: RAMIC, a Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

INTRODUCTION: Retrospective studies report that angiotensin-converting enzyme inhibitors (ACEIs) may reduce the severity of COVID-19, but prospective data on de novo treatment with ACEIs are limited. The RAMIC trial was a randomized, multicenter, placebo-controlled, double-blind, allocation-concealed clinical trial to examine the efficacy of de novo ramipril versus placebo for the treatment of COVID-19. METHODS: Eligible participants were aged 18 years and older with a confirmed diagnosis of SARS-CoV-2 infection, recruited from urgent care clinics, emergency departments, and hospital inpatient wards at eight sites in the USA. Participants were randomly assigned to daily ramipril 2.5 mg or placebo orally in a 2:1 ratio, using permuted block randomization. Analyses were conducted on an intention-to-treat basis. The primary outcome was a composite of mortality, intensive care unit (ICU) admission, or invasive mechanical ventilation by day 14. RESULTS: Between 27 May 2020 and 19 April 2021, a total of 114 participants (51% female) were randomized to ramipril (n = 79) or placebo (n = 35). The overall mean (± SD) age and BMI were 45 (± 15) years and 33 (± 8) kg/m2. Two participants in the ramipril group required ICU admission and one died, compared with none in the placebo group. There were no significant differences between ramipril and placebo in the primary endpoint (ICU admission, mechanical ventilation, or death) (3% versus 0%, p = 1.00) or adverse events (27% versus 29%, p = 0.82). The study was terminated early because of a low event rate and subsequent Emergency Use Authorization of therapies for COVID-19. CONCLUSION: De novo ramipril was not different compared with placebo in improving or worsening clinical outcomes from COVID-19 but appeared safe in non-critically ill patients with COVID-19. TRIAL REGISTRATION: Clinicaltrials.gov NCT04366050.

Catastrophic Antiphospholipid Syndrome Presenting as Congestive Heart Failure in a Patient with Thrombotic Microangiopathy.

Thrombotic microangiopathic syndromes are characterized by thrombus formation leading to microangiopathic hemolytic anemia, thrombocytopenia, and end-organ injury that most often affects the kidney and brain. Patients with thrombotic microangiopathy can also present with cardiac involvement, which has been shown to worsen their prognosis. We describe the case of a 46-year-old woman who presented with acute congestive heart failure as a manifestation of catastrophic antiphospholipid syndrome, which is characterized by rapidly progressing multiorgan involvement. Targeted therapy improved our patient's cardiomyopathy and saved her life. Increased recognition of thrombotic microangiopathy as an underlying pathophysiologic mechanism in heart failure and initiation of timely treatment may help to prevent death in patients with thrombotic microangiopathy.