Clinical trial NCT04380402: Atorvastatin as Adjunctive Therapy in COVID-19
Official title: Prospective Randomized Open-label Trial of Atorvastatin as Adjunctive Treatment of COVID-19
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: COVID-19
Lead sponsor: Mount Auburn Hospital
Sponsor class: OTHER
First posted: 2020-05-08
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Objective: To assess whether adjunctive therapy of COVID-19 infection with atorvastatin reduces the deterioration in hospitalized patients and improves clinical outcome.

Detailed description: COVID-19 is caused by SARS-CoV-2, a β-coronavirus that binds to the zinc peptidase angiotensin-converting enzyme 2 (ACE2). No drug is licensed to treat COVID-19, but adjunctive pharmacologic interventions have been proposed for their immunomodulatory effects, including statins. About 5% of cases are considered critical, with severe respiratory failure as well as myocarditis, and thromboses, and are associated with high fatality rate. Statins affect endothelial dysfunction and have anti-inflammatory and immunomodulatory effects.

This prospective, randomized, open-label trial of atorvastatin as adjunctive treatment of COVID-19 in hospitalized patients aims to study:

1. Will atorvastatin reduce progression to severe or critical COVID-19 disease and death compared to standard care?
2. Will atorvastatin lead to improved clinical outcome of COVID-19 disease at 30 days compared to standard care?

Eligibility criteria: Inclusion Criteria:

* Patient aged 18-85 years, admitted with suspected COVID-19 disease based on clinical criteria (typical upper respiratory symptoms, e.g. runny nose, sore throat, dry cough, associated with COVID-19 infection).

Exclusion Criteria:

* already on chronic statin therapy, known hypersensitivity or adverse events to statins, negative nasopharyngeal (NP) swab for SARS-CoV-2, pregnancy and lactation, need for ICU admission, ALT or AST \>2X upper limit of normal; CPK \> 5x upper limit of normal; and creatinine clearance \<50%, chronic treatment with colchicine, cyclosporin, digoxin, fusidic acid, azole antifungals, niacin.

Primary outcomes:
measure: Proportion of patients that progress to severe or critical requiring ICU admission and/or emergency salvage therapy, or death
timeFrame: 30 days
Secondary outcomes:
measure: Overall score of patients in each arm on Day 7 based on WHO Ordinal Scale for Clinical Improvement
timeFrame: 7 days
measure: Overall score of patients in each arm on Day 30 based on WHO Ordinal Scale for Clinical Improvement
timeFrame: 30 days
measure: Proportions of patients in each arm who test negative for SARS-CoV-2 on Day 7
timeFrame: 7 days
Other outcomes:
Locations:
city: Cambridge
country: United States
facility: Mount Auburn Hospital
state: Massachusetts
Study officials:
affiliation: Mount Auburn Hospital
name: Lin H Chen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet. 2020 Feb 15;395(10223):470-473. doi: 10.1016/S0140-6736(20)30185-9. Epub 2020 Jan 24. No abstract available.
citation: Parihar SP, Guler R, Brombacher F. Statins: a viable candidate for host-directed therapy against infectious diseases. Nat Rev Immunol. 2019 Feb;19(2):104-117. doi: 10.1038/s41577-018-0094-3.
citation: Vandermeer ML, Thomas AR, Kamimoto L, Reingold A, Gershman K, Meek J, Farley MM, Ryan P, Lynfield R, Baumbach J, Schaffner W, Bennett N, Zansky S. Association between use of statins and mortality among patients hospitalized with laboratory-confirmed influenza virus infections: a multistate study. J Infect Dis. 2012 Jan 1;205(1):13-9. doi: 10.1093/infdis/jir695. Epub 2011 Dec 13.
citation: Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential Effects of Coronaviruses on the Cardiovascular System: A Review. JAMA Cardiol. 2020 Jul 1;5(7):831-840. doi: 10.1001/jamacardio.2020.1286.
citation: Fedson DS, Opal SM, Rordam OM. Hiding in Plain Sight: an Approach to Treating Patients with Severe COVID-19 Infection. mBio. 2020 Mar 20;11(2):e00398-20. doi: 10.1128/mBio.00398-20.