Ignite Creation Date:
2024-05-06 @ 3:27 PM
Last Modification Date:
2024-10-26 @ 1:50 PM
Study NCT ID:
NCT04647669
Status:
UNKNOWN
Last Update Posted:
2021-05-13
First Post:
2020-10-15
Brief Title:
World Health Organization WHO COVID-19 Solidarity Trial for COVID-19 Treatments
Sponsor:
The University of The West Indies
Organization:
The University of The West Indies
Study Overview
Official Title:
WHO Public Health Emergency Solidarity Clinical Trial for COVID-19 Treatments
Status:
UNKNOWN
Status Verified Date:
2020-10
Last Known Status:
NOT_YET_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
SOLIDARITY
Brief Summary:
In early 2020 there were no approved anti-viral treatments for COVID19 Infection The SOLIDARITY trial is a multicentre adaptive international randomised trial sponsored by Word Health Organization to determine the efficacy of Remdesivir daily infusion for 10 days or Acalabrutinib orally twice daily for 10 days or Interferon β1adaily injection for 6 days compared with local standard of care in patients admitted to hospital for COVID19 infection on all-cause mortality stratified by severity of disease at the time of randomisation The major secondary outcomes are duration of hospital stay and time to first receiving ventilation or intensive care
Detailed Description:
Terminology The novel coronavirus-induced disease first described in 2019 in China is designated COVID-19 or COVID and the pathogen itself an RNA virus is SARS-coronavirus-2 SARS-CoV-2
Background In early 2020 there were no approved anti-viral treatments for COVID and WHO expert groups advised that four re-purposed drugs Remdesivir Lopinavir given with Ritonavir to slow hepatic degradation Interferon β1a and hydroxychloroquine HCQ should be evaluated in an international randomised trial In addition WHO provided guidelines that local physicians may consider when COVID-19 is suspected on clinical management of severe acute respiratory infection However following an interim analyses the interim results of HCQ vs standard of care and lopinavirritonavir vs standard of care from the SolidarityDiscovery trials the Solidarity trial Executive Group decided to stop the HCQ and the Lopinavirritonavir arms on the 3rd of July 2020 due to futility leaving 3 arms ie remdesivir Interferon β1a and standard of care
On the 6th of August 2020 due to a review of the rationale and clinical evidence the Executive Group of the Steering Committee of the Solidarity trial recommended that a new arm should be opened in the Solidarity trial to evaluate the clinical efficacy of Acalabrutinib
Simplicity of procedures To facilitate collaboration even in hospitals that have become overloaded patient enrolment and randomisation via the internet and all other trial procedures are greatly simplified and no paperwork at all is required Once a hospital has obtained approval electronic entry of patients who have given informed consent takes only a few minutes At the end of it the randomly allocated treatment is displayed on the screen and confirmed by electronic messaging
Randomisation Adults age 18 years recently hospitalised or already in hospital with definite COVID and in the view of the responsible doctor no contra-indication to any of the study drugs will be randomly allocated between
Local standard of care alone OR local standard of care plus one of
Remdesivir daily infusion for 10 days
Acalabrutinib orally twice daily for 10 days
Interferon β1adaily injection for 6 days
Data reported before randomisation Information is entered electronically on
Country hospital from a list of approved hospitals and randomising doctor
Confirmation that informed consent has been obtained
Patient identifiers age and sex
Patient characteristics yesno current smoking diabetes heart disease chronic lung disease chronic liver disease asthma HIV infection active tuberculosis
COVID-19 severity at entry yesno shortness of breath being given oxygen already on a ventilator and if lungs imaged major bilateral abnormality infiltrationspatchy shadowing
Whether any of the study drugs are currently NOT AVAILABLE at the hospital
Exclusion from study entry Patients will not be randomised if in the view of the randomising doctor ANY of the AVAILABLE study drugs are contra-indicated eg because of patient characteristics chronic liver or heart disease or some concurrent medication
Changing management of study patients At all times the patients medical team remains solely responsible for decisions about that patients care and safety Hence if the team decide that deviation from the randomly allocated treatment arm is definitely necessary this should be done
Follow-up When patients die or are discharged follow-up ceases and it is reported
Which study drugs were given and for how many days
Whether ventilation or intensive care was received and if so when it began
Date of discharge or date and cause of death while still in hospital If no report is received within 6 weeks of study entry an electronic reminder is sent
Drug safety Suspected unexpected serious adverse reactions that are life-threatening eg Stevens-Johnson syndrome anaphylaxis aplastic anaemia or anything comparably uncommon and serious must be reported within 24 hours of being diagnosed without waiting for death or discharge
Major outcomes The primary outcome is all-cause mortality subdivided by severity of disease at the time of randomisation The major secondary outcomes are duration of hospital stay and time to first receiving ventilation or intensive care
Data monitoring A global Data and Safety Monitoring Committee will keep the accumulating drug safety results and major outcome results under regular review
Numbers entered The larger the number entered the more accurate the results will be but numbers entered will depend on how the epidemic develops If substantial numbers get hospitalised in the participating centres it may be possible to enter several thousand hospitalised patients with relatively mild disease and a few thousand with severe disease but realistic appropriate sample sizes could not be estimated at the start of the trial and will depend on the evolution of the epidemic
Heterogeneity between populations If a study treatment does affect outcome then this effect could well differ between patients who had severe disease when randomised and those who had less severe disease It could also differ between younger and older patients or between patients in one or another country If sufficient numbers are randomised it may be possible to obtain statistically reliable treatment comparisons within each of several different countries or types of patient
Adaptive design The WHO may decide to add novel treatment arms while the trial is in progress Conversely the WHO may decide to discontinue some treatment arms especially if the Global Data and Safety Monitoring Committee reports based on interim analyses that one of the trial treatments definitely affects mortality
Background In early 2020 there were no approved anti-viral treatments for COVID and WHO expert groups advised that four re-purposed drugs Remdesivir Lopinavir given with Ritonavir to slow hepatic degradation Interferon β1a and hydroxychloroquine HCQ should be evaluated in an international randomised trial In addition WHO provided guidelines that local physicians may consider when COVID-19 is suspected on clinical management of severe acute respiratory infection However following an interim analyses the interim results of HCQ vs standard of care and lopinavirritonavir vs standard of care from the SolidarityDiscovery trials the Solidarity trial Executive Group decided to stop the HCQ and the Lopinavirritonavir arms on the 3rd of July 2020 due to futility leaving 3 arms ie remdesivir Interferon β1a and standard of care
On the 6th of August 2020 due to a review of the rationale and clinical evidence the Executive Group of the Steering Committee of the Solidarity trial recommended that a new arm should be opened in the Solidarity trial to evaluate the clinical efficacy of Acalabrutinib
Simplicity of procedures To facilitate collaboration even in hospitals that have become overloaded patient enrolment and randomisation via the internet and all other trial procedures are greatly simplified and no paperwork at all is required Once a hospital has obtained approval electronic entry of patients who have given informed consent takes only a few minutes At the end of it the randomly allocated treatment is displayed on the screen and confirmed by electronic messaging
Randomisation Adults age 18 years recently hospitalised or already in hospital with definite COVID and in the view of the responsible doctor no contra-indication to any of the study drugs will be randomly allocated between
Local standard of care alone OR local standard of care plus one of
Remdesivir daily infusion for 10 days
Acalabrutinib orally twice daily for 10 days
Interferon β1adaily injection for 6 days
Data reported before randomisation Information is entered electronically on
Country hospital from a list of approved hospitals and randomising doctor
Confirmation that informed consent has been obtained
Patient identifiers age and sex
Patient characteristics yesno current smoking diabetes heart disease chronic lung disease chronic liver disease asthma HIV infection active tuberculosis
COVID-19 severity at entry yesno shortness of breath being given oxygen already on a ventilator and if lungs imaged major bilateral abnormality infiltrationspatchy shadowing
Whether any of the study drugs are currently NOT AVAILABLE at the hospital
Exclusion from study entry Patients will not be randomised if in the view of the randomising doctor ANY of the AVAILABLE study drugs are contra-indicated eg because of patient characteristics chronic liver or heart disease or some concurrent medication
Changing management of study patients At all times the patients medical team remains solely responsible for decisions about that patients care and safety Hence if the team decide that deviation from the randomly allocated treatment arm is definitely necessary this should be done
Follow-up When patients die or are discharged follow-up ceases and it is reported
Which study drugs were given and for how many days
Whether ventilation or intensive care was received and if so when it began
Date of discharge or date and cause of death while still in hospital If no report is received within 6 weeks of study entry an electronic reminder is sent
Drug safety Suspected unexpected serious adverse reactions that are life-threatening eg Stevens-Johnson syndrome anaphylaxis aplastic anaemia or anything comparably uncommon and serious must be reported within 24 hours of being diagnosed without waiting for death or discharge
Major outcomes The primary outcome is all-cause mortality subdivided by severity of disease at the time of randomisation The major secondary outcomes are duration of hospital stay and time to first receiving ventilation or intensive care
Data monitoring A global Data and Safety Monitoring Committee will keep the accumulating drug safety results and major outcome results under regular review
Numbers entered The larger the number entered the more accurate the results will be but numbers entered will depend on how the epidemic develops If substantial numbers get hospitalised in the participating centres it may be possible to enter several thousand hospitalised patients with relatively mild disease and a few thousand with severe disease but realistic appropriate sample sizes could not be estimated at the start of the trial and will depend on the evolution of the epidemic
Heterogeneity between populations If a study treatment does affect outcome then this effect could well differ between patients who had severe disease when randomised and those who had less severe disease It could also differ between younger and older patients or between patients in one or another country If sufficient numbers are randomised it may be possible to obtain statistically reliable treatment comparisons within each of several different countries or types of patient
Adaptive design The WHO may decide to add novel treatment arms while the trial is in progress Conversely the WHO may decide to discontinue some treatment arms especially if the Global Data and Safety Monitoring Committee reports based on interim analyses that one of the trial treatments definitely affects mortality
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None