Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Early Intervention in COVID-19: Favipiravir Verses Standard Care (PIONEER)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04373733
Recruitment Status : Recruiting
First Posted : May 4, 2020
Last Update Posted : July 7, 2020
Sponsor:
Collaborators:
NEAT ID Foundation
FUJIFILM Toyama Chemical Co., Ltd.
Imperial College London
Universitaire Ziekenhuizen Leuven
Information provided by (Responsible Party):
Chelsea and Westminster NHS Foundation Trust

Tracking Information
First Submitted Date  ICMJE May 1, 2020
First Posted Date  ICMJE May 4, 2020
Last Update Posted Date July 7, 2020
Actual Study Start Date  ICMJE May 1, 2020
Estimated Primary Completion Date March 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 1, 2020)
Time to improvement by two points on a seven-category ordinal scale [ Time Frame: Up to 28 days from randomisation ]
Time from randomisation to clinical improvement by two points on a seven-category ordinal scale:
  1. Not hospitalised with resumption of normal activities
  2. Not hospitalised, but unable to resume normal
  3. Hospitalised, not requiring supplemental oxygen
  4. Hospitalised, requiring supplemental oxygen
  5. Hospitalised, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation or both
  6. Hospitalised, requiring ECMO (Extra-corporal membrane oxygenation), invasive mechanical ventilation or both
  7. Death
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 1, 2020)
  • Clinical status on a seven-category ordinal scale (Day 7) [ Time Frame: Day 7 from randomisation ]
    Clinical status of patients at given on the seven-category ordinal scale (see primary endpoint for scale)
  • Clinical status on a seven-category ordinal scale (Day 14) [ Time Frame: Day 14 from randomisation ]
    Clinical status of patients at given on the seven-category ordinal scale (see primary endpoint for scale)
  • Overall survival [ Time Frame: 28 days from randomisation ]
    Survival of patients to end of study
  • Time to improvement by two points on the NEWS score [ Time Frame: Up to 28 days from randomisation ]
    Time from randomisation to improvement by two points on the NEWS score of patient condition, if maintained for 24 hours. For details of NEWS score see https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2
  • Time to improvement by two points on the NEWS element score for temperature [ Time Frame: Up to 28 days from randomisation ]
    Time from randomisation to improvement by two points on the NEWS element score for temperature, if maintained for 24 hours. For details of NEWS score see https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2
  • Time to improvement by two points on the NEWS element score for heartrate [ Time Frame: Up to 28 days from randomisation ]
    Time from randomisation to improvement by two points on the NEWS element score for heartrate, if maintained for 24 hours. For details of NEWS score see https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2
  • Time to improvement by two points on the NEWS element score for respiratory rate [ Time Frame: Up to 28 days from randomisation ]
    Time from randomisation to improvement by two points on the NEWS element score for respiratory rate, if maintained for 24 hours. For details of NEWS score see https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2
  • Time to improvement by two points on the NEWS element score for oxygen saturation. [ Time Frame: Up to 28 days from randomisation ]
    Time from randomisation to improvement by two points on the NEWS element score for oxygen saturation, if maintained for 24 hours. For details of NEWS score see https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2
  • Admission to intensive care [ Time Frame: Up to 28 days from randomisation ]
    Frequency of admission of patients to intensive care
  • Requirement for mechanical ventilation [ Time Frame: Up to 28 days from randomisation ]
    Frequency of requirement to administer mechanical ventilation to patients
  • Requirement for non-invasive ventilation, continuous positive airways pressure or high-flow oxygen [ Time Frame: Up to 28 days from randomisation ]
    Frequency of requirement to administer non-invasive ventilation, continuous positive airways pressure or high-flow oxygen to patients
  • Incidence of bacterial or fungal infection [ Time Frame: Up to 28 days from randomisation ]
    Frequency of culture-confirmed bacterial or fungal infection in patients
  • Incidence of adverse events not directly caused by COVID-19 infection. [ Time Frame: Up to 28 days from randomisation. ]
    Frequency and severity of adverse events in patients not directly attributed by clinicians to COVID-19 infection.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: May 1, 2020)
Readmission to inpatient care [ Time Frame: Up to 28 days from randomisation ]
Frequency of readmission to inpatient care of patients discharged from hospital.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Early Intervention in COVID-19: Favipiravir Verses Standard Care
Official Title  ICMJE A Randomised Controlled Trial of Early Intervention in Patients HospItalised With COVID-19: Favipiravir and StaNdard Care vErsEs Standard CaRe
Brief Summary Currently we do not know how best to treat patients infected with COVID-19. This study is looking at whether randomising participants to either favipiravir or to usual care, can help patients with suspected or proven COVID-19 infection.
Detailed Description

A prospective, randomised, open label study of the combined use of favipiravir and standard clinical care verses standard clinical care alone.

A computer-based software will randomise participants 1:1 to either receive favipiravir and standard medical care or standard medical care alone. The allocated medical regime will commence for 10 days.

Research blood, sputum nose swab and urine samples will be collected at baseline, as well as between day 5 and 10, and between day 14 and 28 to enable comparative analyses.

A COVID-19 antibody test will also be performed 14-28 days after randomisation. In the event of clinically indicated bronchoscopy taking place within 28 days of consent then additional bronchoscopy washing and brushing samples and paired blood sample will be taken for research purposes If a participant is discharged before one of the latter time points, they will be required to return to hospital (provided they are well enough) for the collection of repeat samples.

Participants will be closely monitored whilst taking the study medications. Participants will study exit at subject death or 28 days post-randomisation.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Open-label parallel group randomised control trial. One trial treatment arm and one standard of care comparator arm.
Masking: None (Open Label)
Masking Description:
Open label
Primary Purpose: Treatment
Condition  ICMJE Coronavirus Infection
Intervention  ICMJE
  • Drug: Favipiravir
    Anti-viral
    Other Name: Avigan
  • Other: Standard of care management
    Standard of care management for COVID-19
Study Arms  ICMJE
  • Experimental: Favipiravir & Standard of Care
    Favipiravir: Day 1 1800mg twice per day, Days 2-10 800mg twice per day
    Interventions:
    • Drug: Favipiravir
    • Other: Standard of care management
  • Standard of care
    No trial intervention
    Intervention: Other: Standard of care management
Publications * Not Provided

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 1, 2020)
450
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 31, 2021
Estimated Primary Completion Date March 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Adult participants: Signed informed consent
  2. New admission to hospital for period expected to last ≥ 1 night
  3. Suspected or confirmed COVID-19 infection

    Patients are suspected of COVID-19 infection if they have the following:

    · Influenza like illness (fever ≥37.8°C and at least one of the following respiratory symptoms, which must be of acute onset: persistent cough, hoarseness, nasal discharge or congestion, shortness of breath, sore throat, wheezing or sneezing).

    And

    · Finding from either a chest x-ray or CT suggestive of Covid-19 infection

    And

    · Alternative causes are considered unlikely

  4. For women to be eligible to enter and participate in the study they should be: of non-child-bearing

    • potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or,
    • or of child-bearing potential have a negative pregnancy test at screening and agrees to remain sexually abstinent or use a method of contraception with a failure rate of < 1% per year as indicated in Appendix B during the treatment and for a period of 7 days after the last dose. Hormonal contraceptive methods must be supplemented by a barrier method.
  5. Men who are sexually active must use an adequate method of contraception as listed in Appendix B, for a period of at least 7 days after the last dose

Exclusion Criteria:

  1. Pregnant or breast feeding, due to potential teratogenicity
  2. Hepatic impairment - (AST or ALT > 3.5 x upper limit of normal)
  3. Renal impairment - (eGFR <10ml/ minute)
  4. Known history of retinopathy
  5. Known history of G6PD deficiency
  6. Known history of Myasthenia gravis
  7. QT-prolongation (>450ms in males or >470ms in females, calculated as per investigators discretion)
  8. Presently enrolled in an interventional drug study or on hydroxychloroquine or azithromycin for other therapeutic reasons
  9. Unable to take medication via the oral or nasogastric route
  10. Immunocompromised patients (see Appendix C)
  11. Known sensitivity to favipiravir
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Research Delivery Operations Manager 020 3315 6825 research.development@chewest.nhs.uk
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04373733
Other Study ID Numbers  ICMJE CW002
2020-001449-38 ( EudraCT Number )
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Research team wishes to enable any meta-analyses of COVID-19 trials making appropriate requests. No plan to share IPD has been made at this time.
Responsible Party Chelsea and Westminster NHS Foundation Trust
Study Sponsor  ICMJE Chelsea and Westminster NHS Foundation Trust
Collaborators  ICMJE
  • NEAT ID Foundation
  • FUJIFILM Toyama Chemical Co., Ltd.
  • Imperial College London
  • Universitaire Ziekenhuizen Leuven
Investigators  ICMJE
Principal Investigator: Pallav Shah Chelsea and Westminster NHS Foundation Trust
PRS Account Chelsea and Westminster NHS Foundation Trust
Verification Date July 2020

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