A Randomised Control Trial of Statin and Aspirin as Adjuvant Therapy in Patients with SARS-CoV-2 Infection (RESIST Trial)

BACKGROUND: Statins and aspirin have been advocated for treatment of Covid-19 owing to anti-inflammatory and anti-thrombotic properties and have shown favorable results in observational studies. There is a need for randomized controlled trial. METHODS: We conducted a single-center, four-arm parallel design, open-label randomized controlled trial on RT-PCR positive Covid-19 patients, ≥ 40 years and < 75 years of age, requiring hospitalization [World Health Organization (WHO) Ordinal Scale for Clinical Improvement 3 to 5]. Patients were randomly assigned to either atorvastatin 40 mg (group A), aspirin 75 mg (group B), or both (group C) in addition to standard of care for 10 days or until discharge whichever was earlier or only standard of care (group D). The primary outcome variable was clinical deterioration to WHO Ordinal Scale for Clinical Improvement ≥ 6. The secondary outcome was change in serum inflammatory markers (C-reactive protein and Interleukin-6), and Troponin I. FINDINGS: A total of 900 patients underwent randomization (with Groups A, B, C and D assigned 224, 225, 225 and 226 patients respectively). The primary outcome occurred in 25 (2.8%) patients: 7 (3.2%) in Group A, 3 (1.4%) in Group B, 8 (3.6%) in Group C and 7 (3.2%) in Group D. There was no difference in primary outcome across the study groups (P=0.463). Comparison of all patients who received atorvastatin or aspirin with the control group (Group D) also did not show any benefit [Atorvastatin: HR 1.0 (95% CI 0.41 - 2.46); Aspirin: HR 0.7 (95% CI 0.27 - 1.81)]. The secondary outcomes revealed lower serum IL-6 among patients in Groups B and C. There was no excess of adverse events. INTERPRETATION: Among patients admitted with mild to moderate Covid-19 infection, additional treatment with aspirin, atorvastatin or a combination of the two does not prevent clinical deterioration.