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

Study Overview
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Brief Summary
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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.

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

Conditions
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Covid19, SARS-CoV2 Infection, COVID-19 Pneumonia

Intervention / Treatment
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* Drug: Atorvastatin 40 Mg Oral Tablet
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Atorvastatin<br>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<br>* Patients will receive Atorvastatin 40 mg orally within 24 hrs after hospital admission after evaluation of the clinical and laboratory inclusion criteria.<br>* Other names: Lipitor;|
| Placebo Comparator: Control<br>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<br>* A formulary similar to the drug tablets and labels but without the active ingredients (Atorvastatin).<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atorvastatin, randomized clinical trial