Clinical trial NCT04373733: Early Intervention in COVID-19: Favipiravir Verses Standard Care
Official title: A Randomised Controlled Trial of Early Intervention in Patients HospItalised With COVID-19: Favipiravir and StaNdard Care vErsEs Standard CaRe
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Coronavirus Infection
Keywords: COVID-19
Coronavirus
Lead sponsor: Chelsea and Westminster NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: NEAT ID Foundation
name: FUJIFILM Toyama Chemical Co., Ltd.
name: Imperial College London
First posted: 2020-05-04
Enrollment: 502
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open-label parallel group randomised control trial. One trial treatment arm and one standard of care comparator arm.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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. Presently enrolled in an interventional drug study
4. Unable to take medication via the oral or nasogastric route
5. Known sensitivity Favipiravir

Primary outcomes:
measure: Time from randomisation to a sustained clinical improvement (maintained for 24 hours) by two points on a seven-category ordinal scale or to discharge, whichever occurs first
timeFrame: Up to 28 days from randomisation
Secondary outcomes:
measure: Clinical status on a seven-category ordinal scale (Day 7)
timeFrame: Day 7 from randomisation
measure: Clinical status on a seven-category ordinal scale (Day 14)
timeFrame: Day 14 from randomisation
measure: Overall survival
timeFrame: 28 days from randomisation
measure: Time to improvement by two points on the NEWS score
timeFrame: Up to 28 days from randomisation
measure: Time to improvement by two points on the NEWS element score for temperature
timeFrame: Up to 28 days from randomisation
measure: Time to improvement by two points on the NEWS element score for heartrate
timeFrame: Up to 28 days from randomisation
measure: Time to improvement by two points on the NEWS element score for respiratory rate
timeFrame: Up to 28 days from randomisation
measure: Time to improvement by two points on the NEWS element score for oxygen saturation.
timeFrame: Up to 28 days from randomisation
measure: Admission to intensive care
timeFrame: Up to 28 days from randomisation
measure: Requirement for mechanical ventilation
timeFrame: Up to 28 days from randomisation
measure: Requirement for non-invasive ventilation, continuous positive airways pressure or high-flow oxygen
timeFrame: Up to 28 days from randomisation
measure: Incidence of bacterial or fungal infection
timeFrame: Up to 28 days from randomisation
measure: Incidence of adverse events not directly caused by COVID-19 infection.
timeFrame: Up to 28 days from randomisation.
Other outcomes:
measure: Readmission to inpatient care
timeFrame: Up to 28 days from randomisation
Locations:
city: Porto Alegre
country: Brazil
facility: Grupo Hospitalar Conceição
city: Rio De Janeiro
country: Brazil
facility: Fundação Oswaldo Cruz - Instituto Nacional de Infectologia Evandro Chagas (Fiocruz/INI)
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion, Salvador Zubiran
city: Hull
country: United Kingdom
facility: Hull University Teaching Hospitals NHS Trust - Castle Hill Hospital
city: London
country: United Kingdom
facility: Chelsea and Westminster Hospital
city: London
country: United Kingdom
facility: West Middlesex University Hospital
Study officials:
affiliation: Chelsea and Westminster NHS Foundation Trust
name: Pallav Shah
role: PRINCIPAL_INVESTIGATOR
References: