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World Health Organization (WHO) COVID-19 Solidarity Trial for COVID-19 Treatments (SOLIDARITY)

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ClinicalTrials.gov Identifier: NCT04647669
Recruitment Status : Not yet recruiting
First Posted : December 1, 2020
Last Update Posted : May 13, 2021
Sponsor:
Information provided by (Responsible Party):
The University of The West Indies

Tracking Information
First Submitted Date  ICMJE October 15, 2020
First Posted Date  ICMJE December 1, 2020
Last Update Posted Date May 13, 2021
Estimated Study Start Date  ICMJE June 1, 2021
Estimated Primary Completion Date November 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 28, 2020)
All cause Mortality [ Time Frame: Number of days from hospital admission up to 28 days post discharge ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 28, 2020)
  • Duration of hospital stay [ Time Frame: Number of days from hospital admission to discharge up to 28 days post admission ]
  • Time to first receiving ventilation [ Time Frame: Number of days from hospital admission to day of receiving ventilatory support up to 28 days post admission ]
  • Time to admission to the intensive care unit [ Time Frame: Number of days from hospital admission to day of admission to intensive care unit up to 28 days post admission ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE World Health Organization (WHO) COVID-19 Solidarity Trial for COVID-19 Treatments
Official Title  ICMJE WHO Public Health Emergency "Solidarity" Clinical Trial for COVID-19 Treatments
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 β1a(daily 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 lopinavir/ritonavir vs standard of care from the Solidarity/Discovery trials, the Solidarity trial Executive Group decided to stop the HCQ and the Lopinavir/ritonavir arms on the 3rd of July, 2020 due to futility; leaving 3 arms, i.e., 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 β1a(daily 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 (yes/no): current smoking, diabetes, heart disease, chronic lung disease, chronic liver disease, asthma, HIV infection, active tuberculosis.
  • COVID-19 severity at entry (yes/no): shortness of breath, being given oxygen, already on a ventilator, and, if lungs imaged, major bilateral abnormality (infiltrations/patchy 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 (e.g., because of patient characteristics, chronic liver or heart disease, or some concurrent medication).

Changing management of study patients: At all times the patient's medical team remains solely responsible for decisions about that patient's 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 (e.g., 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Covid19
Intervention  ICMJE
  • Drug: Remdesivir
    200 mg intravenous loading dose on Day 1, and 100mg intravenous once-daily for subsequent doses from Day 2 up to Day 10.
  • Drug: Acalabrutinib
    100 mg capsules twice daily every 12 h for 10 days taken with or without food.
  • Drug: Interferon beta-1a
    Interferon ß-1a will be administered intravenously at the dose of 10 μg once daily for 6 days if oxygen dependent or subcutaneously at 44 ug Day 1, Day 3, and Day 6
  • Other: Standard of Care
    Treatment according to local hospital protocol
Study Arms  ICMJE
  • Placebo Comparator: Local Standard of Care
    Local Standard of Care
    Intervention: Other: Standard of Care
  • Active Comparator: Remdesivir
    Remdesivir (daily infusion for 10 days)
    Intervention: Drug: Remdesivir
  • Active Comparator: Acalabrutinib
    Acalabrutinib (orally twice daily for 10 days)
    Intervention: Drug: Acalabrutinib
  • Active Comparator: Interferon
    Interferon β1a(daily injection for 6 days).
    Intervention: Drug: Interferon beta-1a
Publications * Ansems K, Grundeis F, Dahms K, Mikolajewska A, Thieme V, Piechotta V, Metzendorf MI, Stegemann M, Benstoem C, Fichtner F. Remdesivir for the treatment of COVID-19. Cochrane Database Syst Rev. 2021 Aug 5;8:CD014962. doi: 10.1002/14651858.CD014962.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: November 28, 2020)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date November 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • consenting adults (age ≥18) hospitalised with definite COVID-19
  • Patients without known allergy or contra-indications to any of the of the therapies and without anticipated transfer within 72 hours to a non- study hospital.
  • Patients admitted to a collaborating hospital Exclusion Criteria
  • AVAILABLE study drugs are contra-indicated (e.g., because of patient characteristics, chronic liver or heart disease, or some concurrent medication).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE Jamaica
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04647669
Other Study ID Numbers  ICMJE SRD/ETH/20
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party The University of The West Indies
Study Sponsor  ICMJE The University of The West Indies
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Marvin Reid University of the West Indies
PRS Account The University of The West Indies
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP