ClinicalTrials.gov

History of Changes for Study: NCT04381936
Randomised Evaluation of COVID-19 Therapy (RECOVERY)
Latest version (submitted September 25, 2020) on ClinicalTrials.gov
  • A study version is represented by a row in the table.
  • Select two study versions to compare. One each from columns A and B.
  • Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
  • Click "Compare" to do the comparison and show the differences.
  • Select a version's Submitted Date link to see a rendering of the study for that version.
  • The yellow A/B choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed.
  • Hover over the "Recruitment Status" to see how the study's recruitment status changed.
  • Study edits or deletions are displayed in red.
  • Study additions are displayed in green.
Study Record Versions
Version A B Submitted Date Changes
1 May 7, 2020 None (earliest Version on record)
2 June 3, 2020 Outcome Measures, Arms and Interventions, Study Design, Study Description, Study Status, Study Identification, IPDSharing and Eligibility
3 July 2, 2020 Study Status, Outcome Measures, References, Arms and Interventions, Study Design and Study Description
4 August 24, 2020 Arms and Interventions, Study Status, References, Study Design and Study Description
5 September 25, 2020 Study Status, Arms and Interventions, Study Description, Outcome Measures, Study Design and Sponsor/Collaborators
Comparison Format:

Scroll up to access the controls

Changes (Merged) for Study: NCT04381936
May 7, 2020 (v1) -- June 3, 2020 (v2)

Changes in: Outcome Measures, Arms and Interventions, Study Design, Study Description, Study Status, Study Identification, IPDSharing and Eligibility

Study Identification
Unique Protocol ID: NDPHRECOVERY
Brief Title: Randomized Randomised Evaluation of COVID-19 Therapy (RECOVERY)
Official Title: Randomized Randomised Evaluation of COVID-19 Therapy
Secondary IDs: 2020-001113-21 [EudraCT Number]
ISRCTN50189673 [Registry Identifier: ISRCTN]
Study Status
Record Verification: May June 2020
Overall Status: Recruiting
Study Start: March 19, 2020
Primary Completion: December 2020 [Anticipated]
Study Completion: June 2021 [Anticipated]
First Submitted: May 7, 2020
First Submitted that
Met QC Criteria:
May 7, 2020
First Posted: May 11, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
May 7 June 3, 2020
Last Update Posted: May 11 June 5, 2020 [Actual]
Sponsor/Collaborators
Sponsor: University of Oxford
Responsible Party: Sponsor
Collaborators: UK Research and Innovation
National Institute for Health Research, United Kingdom
Wellcome
Bill and Melinda Gates Foundation
Department for International Development, United Kingdom
Health Data Research UK
Medical Research Council Population Health Research Unit
NIHR Clinical Trials Unit Support Funding
Oversight
U.S. FDA-regulated Drug: No
U.S. FDA-regulated Device: No
Product Exported from U.S.: No
Data Monitoring: Yes
Study Description
Brief Summary: RECOVERY is a randomised trial investigating whether treatment with either Lopinavir-Ritonavir, Hydroxychloroquine, Corticosteroids, Azithromycin, Convalescent plasma or Tocilizumab prevents death in patients with COVID-19.
Detailed Description:

BACKGROUND: In early 2020, as this protocol was being developed, there were no approved treatments for COVID-19, a disease induced by the novel coronavirus SARSCoV-2 that emerged in China in late 2019. The UK New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) advised that several possible treatments should be evaluated, including Lopinavir-Ritonavir, low-dose corticosteroids, and Hydroxychloroquine. These groups also advised that other treatments will soon emerge that require evaluation. A World Health Organization (WHO) expert group issued broadly similar advice.

ELIGIBILITY AND RANDOMISATION: This protocol describes a randomised trial among patients hospitalised for COVID-19. All eligible patients are randomly allocated between several treatment arms, each to be given in addition to the usual standard of care in the participating hospital: No additional treatment vs Lopinavir-Ritonavir vs Low-dose Corticosteroids vs Hydroxychloroquine vs Azithromycin. In a factorial design, eligible patients are allocated simultaneously to no additional treatment vs convalescent plasma. The study allows a second subsequent randomisation for patients with progressive COVID-19 (evidence of hyper-inflammatory state): No additional treatment vs Tocilizumab. For patients for whom not all the trial arms are appropriate or at locations where not all are available, randomisation will be between fewer arms.

ADAPTIVE DESIGN: The interim trial results will be monitored by an independent Data Monitoring Committee (DMC). The most important task for the DMC will be to assess whether the randomised comparisons in the study have provided evidence on mortality that is strong enough (with a range of uncertainty around the results that is narrow enough) to affect national and global treatment strategies. In such a circumstance, the DMC will inform the Trial Steering Committee who will make the results available to the public and amend the trial arms accordingly. New trial arms can be added as evidence emerges that other candidate therapeutics should be evaluated.

OUTCOMES: The main outcomes will be death, discharge, need for ventilation and need for renal replacement therapy. For the main analyses, follow-up will be censored at 28 days after randomisation. Additional information on longer term outcomes may be collected through review of medical records or linkage to medical databases such as those managed by NHS Digital and equivalent organisations in the devolved nations.

SIMPLICITY OF PROCEDURES: To facilitate collaboration, even in hospitals that suddenly become overloaded, patient enrolment (via the internet) and all other trial procedures are greatly streamlined. Informed consent is simple and data entry is minimal. Randomisation via the internet is simple and quick, at the end of which the allocated treatment is displayed on the screen and can be printed or downloaded. Follow-up information is recorded at a single timepoint and may be ascertained by contacting participants in person, by phone or electronically, or by review of medical records and databases.

DATA TO BE RECORDED: At randomisation, information will be collected on the identity of the randomising clinician and of the patient, age, sex, major co-morbidity, pregnancy, COVID-19 onset date and severity, and any contraindications to the study treatments. The main outcomes will be death (with date and probable cause), discharge (with date), need for ventilation (with number of days recorded) and need for renal replacement therapy. Reminders will be sent if outcome data have not been recorded by 28 days after randomisation. Suspected Unexpected Serious Adverse Reactions (SUSARs) to one of the study medication (eg, Stevens-Johnson syndrome, anaphylaxis, aplastic anaemia) will be collected and reported in an expedited fashion. Other adverse events will not be recorded but may be available through linkage to medical databases.

NUMBERS TO BE RANDOMISED: The larger the number randomised the more accurate the results will be, but the numbers that can be randomised will depend critically on how large the epidemic becomes. If substantial numbers are hospitalised in the participating centres then it may be possible to randomise several thousand with mild disease and a few thousand with severe disease, but realistic, appropriate sample sizes could not be estimated at the start of the trial.

HETEROGENEITY BETWEEN POPULATIONS: If sufficient numbers are studied, it may be possible to generate reliable evidence in certain patient groups (e.g. those with major comorbidity or who are older). To this end, data from this study may be combined with data from other trials of treatments for COVID-19, such as those being planned by the WHO.

ADD-ON STUDIES: Particular countries or groups of hospitals, may well want to collaborate in adding further measurements or observations, such as serial virology, serial blood gases or chemistry, serial lung imaging, or serial documentation of other aspects of disease status. While well-organised additional research studies of the natural history of the disease or of the effects of the trial treatments could well be valuable (although the lack of placebo control may bias the assessment of subjective side-effects, such as gastrointestinal problems), they are not core requirements.

Conditions
Conditions: Severe Acute Respiratory Syndrome
Keywords: COVID-19
SARS-CoV-2
SARS coronavirus 2
SARS
Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2/Phase 3
Interventional Study Model: Parallel Factorial Assignment

Main randomisation (part A): Eligible patients will be randomly allocated between the available 5 treatment arms.

Main randomisation (part B): Simultaneously, eligible patients will be randomly allocated between convalescent plasma or no additional treatment.

Subsequent randomisation: Participants with progressive COVID-19 (as evidenced by hypoxia and an inflammatory state) may undergo an optional second randomisation.

Number of Arms: 6 7
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 12000 [Anticipated]
Arms and Interventions
Arms Assigned Interventions
No Intervention: Standard Care
Patient receives usual hospital care
Active Comparator: Low dose corticosteroids
First (main) randomisation part A
Drug: Corticosteroid
Corticosteroid in the form of dexamethasone administered as an oral (liquid or tablets) or intravenous preparation 6 mg once daily for 10 days. In pregnancy or breastfeeding women, prednisolone 40 mg administered by mouth (or intravenous hydrocortisone 80 mg twice daily) should be used instead of dexamethasone.
Active Comparator: Hydroxychloroquine
First (main) randomisation part A
Drug: Hydroxychloroquine
Hydroxychloroquine by mouth for a total of 10 days (see Protocol for timing and dosage).
Active Comparator: Lopinavir-Ritonavir
First (main) randomisation part A
Drug: Lopinavir-Ritonavir
Lopinavir 400mg-Ritonavir 100mg by mouth (or nasogastric tube) every 12 hours for 10 days.
Active Comparator: Azithromycin
First (main) randomisation part A
Drug: Azithromycin
Azithromycin 500mg by mouth (or nasogastric tube) or intravenously once daily for 10 days.
Active Comparator: Convalescent plasma
First (main) randomisation part B
Biological: Convalescent plasma
Single unit of ABO compatible convalescent plasma (275mls +/- 75 mls) intravenous per day on study days 1 (as soon as possible after randomisation) and 2 (with a minimum of 12 hour interval between 1st and 2nd units).
Active Comparator: Tocilizumab
Participants with progressive COVID-19 (as evidenced by hypoxia and an inflammatory state) may undergo an optional second subsequent randomisation between Tocilizumab and no additional treatment.
Drug: Tocilizumab
Tocilizumab by intravenous infusion with the dose determined by body weight (see Protocol for dosage)
Outcome Measures
Primary Outcome Measures:
1. All-cause mortality
For each pairwise comparison with the 'no additional treatment' arm, the primary objective is to provide reliable estimates of the effect of study treatments on all-cause mortality.

[Time Frame: Within 28 days after randomisation]
Secondary Outcome Measures:
2. Duration of hospital stay
To assess the effects of study treatment on number of days stay in hospital

[Time Frame: Within 28 days and up to 6 months after the main randomisation]
3. Need for (and duration of) ventilation
To assess the effects of study treatment on number of patients who needed ventilation and the number of days it was required

[Time Frame: Within 28 days and up to 6 months after the main randomisation]
4. Need for renal replacement Composite endpoint of death or need for mechanical ventilation or ECMO
To assess the effects of study treatment on number of patients who needed renal replacement therapy Among patients not on ventilation at baseline, the number of patients with a composite endpoint of death or need for mechanical ventilation or ECMO.

[Time Frame: Within 28 days and up to 6 months after the main randomisation]
Other Pre-specified Outcome Measures:
5. Need for renal replacement
To assess the effects of study treatment on number of patients who needed renal replacement therapy

[Time Frame: Within 28 days and up to 6 months after the main randomisation]
6. Development of new major cardiac arrythmias
To assess the effects of study treatment on number of patients who develop new major cardiac arrythmias

[Time Frame: Within 28 days and up to 6 months after the main randomisation]
Eligibility
Minimum Age:
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • (i) Hospitalised
  • (ii) SARS-CoV-2 infection (clinically suspected or laboratory confirmed)
  • (iii) No medical history that might, in the opinion of the attending clinician, put the patient at significant risk if he/she were to participate in the trial

Exclusion Criteria:

  • If the attending clinician believes that there is a specific contra-indication to one of the active drug treatment arms (see Protocol Appendix 2; section 9.2 8.2 and Appendix 3; section 9.3 8.3 for children) or that the patient should definitely be receiving one of the active drug treatment arms then that arm will not be available for randomisation for that patient. For patients who lack capacity, an advanced directive or behaviour that clearly indicates that they would not wish to participate in the trial would be considered sufficient reason to exclude them from the trial.
Contacts/Locations
Central Contact: Richard Haynes
Telephone: +44 (0)1865 743743
Email: recoverytrial@ndph.ox.ac.uk
Study Officials: Peter W Horby
Principal Investigator
University of Oxford
Locations: United Kingdom
Nuffield Department of Population Health, University of Oxford
[Recruiting]
Oxford, United Kingdom, OX3 7LF
Contact: Peter W Horby recoverytrial@ndph.ox.ac.uk
Principal Investigator: Peter W Horby
Principal Investigator: Martin Landray
Principal Investigator: Wei Shen Lim
Principal Investigator: Kenneth Baillie
Principal Investigator: Richard Haynes
Principal Investigator: Ed Juszczak
Principal Investigator: Thomas Jaki
IPDSharing
Plan to Share IPD: Yes
The data-sharing plans for this study will be made available at a later date.
Supporting Information:
Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame:
Access Criteria:
Proposals for substudies must be approved by the Trial Steering Committee. Procedures for accessing the data for this study are available on https://www.ndph.ox.ac.uk/data-access
URL: https://www.ndph.ox.ac.uk/data-access
References
Citations:
Links: Description: RECOVERY Trial website (the Protocol and other trial documents can be downloaded from this website)
Available IPD/Information:

Scroll up to access the controls Scroll to the Study top

U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services