Coronavirus Response - Active Support for Hospitalised Covid-19 Patients

Study Overview
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Brief Summary
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The CRASH-19 trial is a multinational, open-label, factorial, randomised trial in adults hospitalised with suspected or confirmed acute COVID-19 infection.

Detailed Description
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We will evaluate the effect of aspirin (150mg once daily), losartan (100mg once daily), and simvastatin (80mg once daily) in patients with COVID-19 infection. Eligible patients will be randomly allocated to one of eight study arms (aspirin only; losartan only; simvastatin only; aspirin and losartan; aspirin and simvastatin; losartan and simvastatin; aspirin, losartan and simvastatin; standard care only). Trial treatments are given in addition to the usual standard of care at the study hospital. Treatment will be started as soon as possible after randomisation and will continue until death, discharge or 28 days after randomisation, whichever occurs first.

Official Title
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Aspirin, Losartan and Simvastatin in Hospitalised COVID-19 Patients: a Multinational Randomised Open-label Factorial Trial

Conditions
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Covid-19

Intervention / Treatment
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* Drug: Aspirin
* Drug: Losartan
* Drug: Simvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults age 40 years and older with suspected or confirmed acute COVID-19 infection. Acute COVID-19 infection is suspected in the presence of a fever and at least one symptom of respiratory disease e.g. cough, difficulty breathing, signs of hypoxia. The clinician may suspect COVID-19 infection if i) the patient lives in or has recently travelled to an area with COVID-19 transmission; ii) the patient had recent contact with a confirmed or probable COVID-19 case, or iii) no alternative diagnosis fully explains the clinical presentation requiring hospitalisation Exclusion Criteria: Women known to be pregnant Patients hospitalised without symptoms of acute COVID-19 infection should not be recruited even if they test positive for COVID-19 Patients already receiving mechanical ventilation Patients with a definite indication or contraindication for any of the trial treatments. Patients who are very severely frail (completely dependent and approaching end of life who typically they could not recover even from a mild illness) or terminally ill should not be recruited.

Ages Eligible for Study
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Minimum Age: 40 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: Factorial Assignment
Interventional Model Description: 2 x 2 x 2
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard care<br>Usual standard of care at the study hospital | |
| Experimental: Aspirin<br>Aspirin 150mg once daily | Drug: Aspirin<br>* Aspirin 150mg<br>|
| Experimental: Losartan<br>Losartan 100mg once daily. Dose may be stopped or reduced if patient is hypotensive and can be restarted anytime during the treatment period. | Drug: Losartan<br>* Losartan 100mg<br>|
| Experimental: Simvastatin<br>Simvastatin 80mg once daily | Drug: Simvastatin<br>* Simvastatin 80mg<br>|
| Experimental: Aspirin and Losartan<br>Aspirin 150mg once daily and Losartan 100mg once daily. Losartan dose may be stopped or reduced if patient is hypotensive and can be restarted anytime during the treatment period. | Drug: Aspirin<br>* Aspirin 150mg<br>Drug: Losartan<br>* Losartan 100mg<br>|
| Experimental: Aspirin and Simvastatin<br>Aspirin 150mg once daily and Simvastatin 80mg once daily | Drug: Aspirin<br>* Aspirin 150mg<br>Drug: Simvastatin<br>* Simvastatin 80mg<br>|
| Experimental: Losartan and Simvastatin<br>Losartan 100mg once daily and Simvastatin 80mg once daily. Losartan dose may be stopped or reduced if patient is hypotensive and can be restarted anytime during the treatment period. | Drug: Losartan<br>* Losartan 100mg<br>Drug: Simvastatin<br>* Simvastatin 80mg<br>|
| Experimental: Aspirin, Losartan and Simvastatin<br>Aspirin 150mg once daily, Losartan 100mg once daily and Simvastatin 80mg once daily. Losartan dose may be stopped or reduced if patient is hypotensive and can be restarted anytime during the treatment period. | Drug: Aspirin<br>* Aspirin 150mg<br>Drug: Losartan<br>* Losartan 100mg<br>Drug: Simvastatin<br>* Simvastatin 80mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death | Cause of death will be described | up to 28 days of randomisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial infarction |  | up to 28 days of randomisation | 
| Congestive cardiac failure |  | up to 28 days of randomisation | 
| Severe cardiac arrythmia |  | up to 28 days of randomisation | 
| Myocarditis |  | up to 28 days of randomisation | 
| Respiratory failure including ARDS |  | up to 28 days of randomisation | 
| Viral pneumonitis |  | up to 28 days of randomisation | 
| Acute renal failure |  | up to 28 days of randomisation | 
| Sepsis |  | up to 28 days of randomisation | 
| Stroke |  | up to 28 days of randomisation | 
| Gastrointestinal bleeding |  | up to 28 days of randomisation | 
| Receipt of non invasive or mechanical ventilation |  | up to 28 days of randomisation | 
| Ability to self care at hospital discharge |  | up to 28 days of randomisation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adult Respiratory Distress Syndrome, Pneumonia, Myocardial infarction