Statin and aspirin as adjuvant therapy in hospitalised patients with SARS-CoV-2 infection: a randomised clinical trial (RESIST trial)
Nirmal Ghati, Sushma Bhatnagar, Manjit Mahendran, Abhishek Thakur, Kshitij Prasad, Devesh Kumar, Tanima Dwivedi, Kalaivani Mani, Pawan Tiwari, Ritu Gupta, Anant Mohan, Anita Saxena, Randeep Guleria, Siddharthan Deepti
BMC Infectious Diseases, doi:10.1186/s12879-022-07570-5
Background: Statins and aspirin have been proposed for treatment of COVID-19 because of their anti-inflammatory and anti-thrombotic properties. Several observational studies have shown favourable results. There is a need for a randomised controlled trial.
Methods: In this single-center, open-label, randomised controlled trial, 900 RT-PCR positive COVID-19 patients requiring hospitalisation, were randomly assigned to receive either atorvastatin 40 mg (Group A, n = 224), aspirin 75 mg (Group B, n = 225), or both (Group C, n = 225) in addition to standard of care for 10 days or until discharge whichever was earlier or only standard of care (Group D, n = 226). The primary outcome variable was clinical deterioration to WHO Ordinal Scale for Clinical Improvement ≥ 6. The secondary outcome was change in serum C-reactive protein, interleukin-6, and troponin I.
Results: 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) P = 0.99; Aspirin: HR 0.7 (95% CI 0.27-1.81) P = 0.46]. The secondary outcomes revealed lower serum interleukin-6 levels among patients in Groups B and C. There was no excess of adverse events. Conclusions: 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.
Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1186/ s12879-022-07570-5. Additional file 1. eFigure 1. Institute Covid-19 treatment protocol. eFigure 2. Probability of having WHO Ordinal Scale for Clinical Improvement < 6 in the study groups over time (Intension-to-treat analysis). eFigure 3. Probability of having WHO Ordinal Scale for Clinical Improvement < 6 in the study groups over time (Per protocol analysis). eFigure 4. Probability of having WHO Ordinal Scale for Clinical Improvement < 6 in the study groups over time (as treated analysis). eTable 1. Distribution of adverse events in the study groups. Author contributions NG: Conceptualization, Methodology, Data curation, Visualization, Writing-Original draft preparation, Writing-Review and Editing; SuB: Project Administration, Supervision, Resource; MM, AT,KP, DK: Data curation, Methodology, Investigation; PT, TD: Methodology, Investigation; KM: Software, Formal Analysis, Validation; RiG, AM, RG, AS: Supervision, Resources; SD: Project Administration, Supervision, Conceptualization, Methodology, Investigation, Data curation, Visualization, Writing-Original draft preparation, Writing-Review and Editing. NG, SD have verified the underlying data. All authors have read and approved the final manuscript.
Funding There was no funding source for this study.
Declarations Ethics approval and consent to participate The trial was conducted in accordance..
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