Atorvastatin for Reduction of 28-day Mortality in COVID-19: RCT (COVID-STAT)

Atorvastatin in Hospitalized COVID-19 Patients: A Randomized, Double-blinded, Placebo-Controlled, Clinical Trial

This randomized placebo-controlled double-blinded clinical trial aims to test the efficacy of administering atorvastatin 40 mg to hospitalized COVID-19 patients for 28 days on the all-cause 28-day mortality.

Study Overview

• Status: Active, not recruiting
• Conditions: Covid19; SARS-CoV2 Infection; COVID-19 Pneumonia
• Intervention / Treatment: Drug: Atorvastatin 40 Mg Oral Tablet; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 220
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Aldakahlia
    • Mansoura, Aldakahlia, Egypt, 35516
      • Mansoura university hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• We will include adult patients (≥18 years old) with severe and critical COVID19 admitted to the COVID19 Mansoura University isolation hospital. We will include patients who are PCR-confirmed, clinically or radiologically diagnosed with COVID19.

Cases are defined as severe or critical according to the WHO definition (19); where critical cases have ARDS, or sepsis, septic shock or pulmonary embolism, acute coronary syndrome, or acute stroke, while severe cases have the clinical signs of severe pneumonia and SpO2 <90% on room air, or RR <30 breaths/min without any critical criteria.

Exclusion Criteria:

• chronic statin use, serum creatine kinase (sr CK) > 5 times the upper limit of normal (ULN), serum transaminases > 5 times ULN, acute hepatic failure, chronic liver disease (Child-Pugh Classification C), history of rhabdomyolysis or myopathies, severe renal impairment not receiving renal replacement therapy (estimated Cr cl< 30 ml\min ), pregnant and lactating women, patients who are expected to die within 48 hours, or patients on chronic colchicine, cyclosporines, or ritonavir.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Atorvastatin; All patients will be randomized to receive atorvastatin 40 mg once daily orally for a maximum of 28 days. All patients will receive the standard of care according to recent local hospital protocol. Antiviral treatment will be allowed and will be reported. Administration in unconscious or ventilated patients: The patients will receive the drug (divided into 4 quadrants) through a nasogastric tube.	Drug: Atorvastatin 40 Mg Oral Tablet; Patients will receive Atorvastatin 40 mg orally within 24 hrs after hospital admission after evaluation of the clinical and laboratory inclusion criteria.; Other Names: Lipitor; 134523-00-5; ATORVASTATIN CALCIUM
Placebo Comparator: Control; All patients will be randomized to receive the placebo once daily orally for a maximum of 28 days. All patients will receive the standard of care according to recent local hospital protocol. Antiviral treatment will be allowed and will be reported. Administration in unconscious or ventilated patients: The patients will receive the drug through a nasogastric tube. Placebo will resemble the original drug as regards the drug package, the tablet color, consistency, and size.	Other: Placebo; A formulary similar to the drug tablets and labels but without the active ingredients (Atorvastatin).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mortality	all-cause mortality	28 days after randomization
mortality	all-cause mortality	6 months after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of invasive mechanical ventilation (IMV)	incidence	28 days or primary hospital stay
duration of invasive mechanical ventilation (IMV)	duration in days	28 days or primary hospital stay
Time to clinical improvement	2 points reduction in the WHO disease ordinal progression scale or discharge, whatever happens first.	28 days or primary hospital stay
serious adverse effects	any event that leads to discontinuation of the drug	28 days after start of the drug
Intensive Care length of stay	duration in days	28 days or primary hospital stay
acute kidney injury	Increase in Scr by >/ 0.3 mg/ dl in 48 hr or Increase in Scr by >/ 50% in 7 days or Oliguria for >/ 6 hours.	28 days or primary hospital stay
status at hospital discharge	dead or alive	through study completion, an average of 9 months
Hospital length of stay	Length of hospital stay in days	through study completion, an average of 9 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
C-Reactive Protein	as inflammatory marker	on days 3, 7, 14, and 28 after randomization/ if still hospitalized
Sequential Organ Failure Assessment scale	SOFA scale	on days 3, 7, 14, and 28 after randomization/ if still hospitalized
COVID Disease progression score	according to the January 2021 WHO update	on days 3, 7, 14, and 28 after randomization/ if still hospitalized

Collaborators and Investigators

• Sponsor: Mansoura University
• Investigators: Study Director: Moataz M Emara, MD, EDAIC, Mansoura University - Faculty of Medicine

Publications and helpful links

General Publications

• Emara MM, Elsawy NH, Abdelaaty KM, Elhamaky AS, Eltahan NH. Atorvastatin for reduction of 28-day mortality in hospitalized COVID-19 patients: study protocol for a randomized, double-blinded, placebo-controlled, clinical trial. Trials. 2022 Aug 8;23(1):636. doi: 10.1186/s13063-022-06619-9.

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2021
• Primary Completion (Anticipated): November 1, 2021
• Study Completion (Anticipated): April 1, 2022

Study Registration Dates

• First Submitted: July 1, 2021
• First Submitted That Met QC Criteria: July 2, 2021
• First Posted (Actual): July 7, 2021

Study Record Updates

• Last Update Posted (Actual): October 25, 2021
• Last Update Submitted That Met QC Criteria: October 22, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Atorvastatin; randomized clinical trial
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: R.21.04.1300.R1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will make the anonymous individual data available at reasonable request after publication. Patient confidentiality will be kept safe.
• IPD Sharing Time Frame: will be updtaed shortly
• IPD Sharing Access Criteria: will be updated shortly

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No