Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202006473370201 Date of Approval: 17/06/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Coronavirus Response - Active Support for Hospitalised COVID-19 patients
Official scientific title Aspirin, losartan and simvastatin in hospitalised COVID-19 patients: a multinational randomised open-label factorial trial
Brief summary describing the background and objectives of the trial BACKGROUND: Patients with COVID-19 infection typically present with fever, muscle aches and a dry cough. Although most have a mild illness, older people and those with chronic health problems, particularly cardiovascular disease, can develop a severe viral pneumonia with a poor prognosis. Cardiac complications, in particular myocardial infarction and heart failure are common in viral pneumonia and the high troponin levels in COVID-19 non-survivors strongly suggest that cardiac events are an important cause of death. A cohort study of 416 patients admitted to hospital in Wuhan with COVID-19 found that cardiac injury, defined as high sensitivity troponin 1 levels >99% upper reference limit, was seen in 20% of patients. These patients were more likely to receive mechanical ventilation (22.0% vs 4.2%; P < 0.001) and were more likely to die (51.2% vs 4.5%; P < 0.001). Acute respiratory distress syndrome (ARDS) is a clinical syndrome often seen in patients with viral pneumonia and is particularly common in severe COVID-19 infection. The incubation period (time from infection to first symptoms) for COVID-19 is about 5 days. The time from symptom onset to hospital admission is about 6 days. By the time patients are admitted they have been infected with the virus for over 10 days and have an established viral pneumonia. At the time of protocol development, there were no approved anti-viral treatments for COVID-19. Although trials have started, supportive care is the mainstay of management. Optimising the effectiveness of supportive care is therefore of utmost importance and is the objective of this trial. AIM: The CRASH-19 trial will assess the effectiveness and safety of supportive care interventions for patients hospitalised with suspected or confirmed acute COVID-19 infection with a focus on cardiac and pulmonary protection. We will evaluate the effects of aspirin, the angiotensin receptor blocker losartan, and simvastatin compared with standard care.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) CRASH19
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied COVID-19
Purpose of the trial Treatment: Drugs
Anticipated trial start date 30/04/2020
Actual trial start date 30/04/2021
Anticipated date of last follow up 31/05/2021
Actual Last follow-up date 31/08/2021
Anticipated target sample size (number of participants) 10000
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Permuted block randomization Central randomisation by phone/fax Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Usual standard of care at the study hospital up to 28 days Usual standard of care at the study hospital 1250 Active-Treatment of Control Group
Experimental Group aspirin 150mg once daily up to 28 days aspirin 1250
Experimental Group losartan Losartan 100mg once daily. Dose may be stopped or reduced if patient is hypotensive and can be restarted anytime during the treatment period up to 28 days Losartan 1250
Experimental Group simvastatin 80mg once daily up to 28 days simvastatin 1250
Experimental Group Aspirin and Losartan 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. up to 28 days Aspirin and Losartan 1250
Experimental Group Aspirin and Simvastatin Aspirin 150mg once daily and Simvastatin 80mg once daily up to 28 days Aspirin and Simvastatin 1250
Experimental Group Losartan and Simvastatin 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. up to 28 days Losartan and Simvastatin 1250
Experimental Group AspirinLosartanSimvastatin 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. up to 28 days Aspirin, Losartan and Simvastatin 1250
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Adults age 40 years and older with suspected or confirmed acute COVID-19 infection (We use the following WHO criteria for a suspected case: A. A patient with acute respiratory illness (fever and at least one sign or symptom of respiratory disease, e.g., cough, shortness of breath), AND a history of travel to or residence in a location reporting community transmission of COVID-19 disease during the 14 days prior to symptom onset; OR B. A patient with any acute respiratory illness AND having been in contact with a confirmed or probable COVID-19 case in the last 14 days prior to symptom onset; OR C. A patient with severe acute respiratory illness (fever and at least one sign/symptom of respiratory disease, e.g., cough, shortness of breath; AND requiring hospitalization) AND in the absence of an alternative diagnosis that fully explains the clinical presentation.) requiring hospitalisation 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 via an endotracheal tube Patients already receiving any of the trial treatments 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. 80 and over: 80+ Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 40 Year(s) 100 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 01/05/2020 LSHTM Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Keppel Street London 111111111 United Kingdom
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome In-hopsital death. Cause of death will be described up to 28 days of randomisation
Secondary Outcome myocardial infarction, cardiac failure, severe cardiac arrhythmia, myocarditis, respiratory failure including ARDS, viral pneumonitis, acute renal failure, sepsis, stroke, gastrointestinal bleeding, receipt of non-invasive or mechanical ventilation requiring endotracheal intubation, ability to self-care at hospital discharge and time to hospital discharge. up to 28 days after randomsiation
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
University College Hospital Ibadan, Oyo Ibadan Nigeria
Shifa Tameer e Millat University Gujar Khan Campus, near Rural Health Center Mandra Rawalpindi Pakistan
Lagos University Teaching Hospital Ishaga Rd, Idi-Araba Lagos Nigeria
Olabisi Onabanjo University Teaching Hospital Hospital Road Sagamu Nigeria
Irrua Specialist Hospital KM 87 Benin Auchi Rd Irrua Nigeria
Ladoke Akintola University of Technology P.M.B 4000, Ogbomoso Oyo State Nigeria
Onikan Isolation Centre Tafewa Balewa Square, Lagos Island Lagos Nigeria
National Hospital Abuja 265 Independence Ave, Central Business District Abuja Nigeria
University of Abuja Teaching Hospital Gwagwalada-Zuba Gwagwalada Nigeria
Federal Medical Centre Katsina Murtala Muhammad Way, Jibia Bypass P.M.B 2121 Katsina Nigeria
Abubakar Tafawa Balewa University Teaching Hospital Hospital Road off Yandoka Street, PMB 0117 Bauchi Nigeria
Ahmadu Bello University Teaching Hospital Sabon Gari Zaria Kaduna Nigeria
Infectious Disease Hospital Akure Igbatoro road Akure Ondo State Nigeria
Infectious Disease Centre Sobi Specialist Hospital Alagbado Road Ilorin Nigeria
Infectious Disease Hospital Yaba Mainland Hospital Rd, Yaba 100001 Lagos Nigeria
Allied Hospital Faisalabad Unit III Dr. Tusi Rd Faisalabad Pakistan
Benazir Bhutto Hospital Unit II Murree Road Rawalpindi Pakistan
Jinnah Postgraduate Medical Centre Rafiqui Shaheed Road Karachi Pakistan
Services Hospital Lahore Medical Unit 3 Shadman Jail Road Lahore Pakistan
Pakistan Institute of Medical Sciences Islamabad Ibn-e-Sina Rd Islamabad Pakistan
Hayatabad Medical Complex Phase 4 Hayatabad Peshawar Pakistan
FUNDING SOURCES
Name of source Street address City Postal code Country
This trial is supported by a grant from LSHTM. The LSHTM CTU is supported by NIHR Clinical Trials Unit Support Funding. LSHTM, Keppel Street London 111111111 United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor London School of Hygiene and Tropical Medicine Keppel Street London 111111111 United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Ian Roberts crash19@lshtm.ac.uk 00442072994684 Keppel Street
City Postal code Country Position/Affiliation
London United Kingdom Codirector of the CTU. Professor of epidemiology and public health
Role Name Email Phone Street address
Public Enquiries Danielle Beaumont crash19@lshtm.ac.uk 00442072994684 Keppel Street
City Postal code Country Position/Affiliation
London United Kingdom Senior Trial Manager
Role Name Email Phone Street address
Scientific Enquiries Haleema Shakur Still crash19@lshtm.ac.uk 00442072994684 Keppel Street
City Postal code Country Position/Affiliation
London United Kingdom CTU codirector. Professor of global health clinical trials
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes As many sites will contribute to this trial, individual sites cannot restrict the publication of the manuscript relating to the outcomes of this trial. All anonymised data from this trial will be made freely available on our data sharing site: http://freebird.lshtm.ac.uk. Informed Consent Form,Statistical Analysis Plan,Study Protocol Within 6 months or sooner of publication Log-in required for the sole purpose to monitor data download.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
http://freebird.lshtm.ac.uk No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information