Early Intervention in COVID-19: Favipiravir Verses Standard Care

Coronavirus Infection Clinical Trial

— PIONEER  

Official title:

A Randomised Controlled Trial of Early Intervention in Patients HospItalised With COVID-19: Favipiravir and StaNdard Care vErsEs Standard CaRe

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04373733
• Other study ID #: CW002
• Secondary ID: 2020-001449-38
• Status: Completed
• Phase: Phase 3
• Start date: May 1, 2020
• Est. completion date: June 25, 2021

Study information

• Verified date: November 2021
• Source: Chelsea and Westminster NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 502
• Est. completion date: June 25, 2021
• Est. primary completion date: June 25, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Coronavirus Infection
• Coronavirus Infections
• COVID-19

Intervention

Drug:
• Favipiravir
Anti-viral

Other:
• Standard of care management
Standard of care management for COVID-19

Locations

Country	Name	City	State
Brazil	Grupo Hospitalar Conceição	Porto Alegre
Brazil	Fundação Oswaldo Cruz - Instituto Nacional de Infectologia Evandro Chagas (Fiocruz/INI)	Rio De Janeiro
Mexico	Instituto Nacional de Ciencias Medicas y Nutricion, Salvador Zubiran	Mexico City
United Kingdom	Hull University Teaching Hospitals NHS Trust - Castle Hill Hospital	Hull
United Kingdom	Chelsea and Westminster Hospital	London
United Kingdom	West Middlesex University Hospital	London

Sponsors (4)

Lead Sponsor	Collaborator
Chelsea and Westminster NHS Foundation Trust	FUJIFILM Toyama Chemical Co., Ltd., Imperial College London, NEAT ID Foundation

Countries where clinical trial is conducted

Brazil,  Mexico,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Readmission to inpatient care	Frequency of readmission to inpatient care of patients discharged from hospital.	Up to 28 days from randomisation
Primary	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	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; The seven-category ordinal scale is : Not hospitalised with resumption of normal activities; Not hospitalised, but unable to resume normal; Hospitalised, not requiring supplemental oxygen; Hospitalised, requiring supplemental oxygen; Hospitalised, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation or both; Hospitalised, requiring ECMO (Extra-corporal membrane oxygenation), invasive mechanical ventilation or both; Death	Up to 28 days from randomisation
Secondary	Clinical status on a seven-category ordinal scale (Day 7)	Clinical status of patients at given on the seven-category ordinal scale (see primary endpoint for scale)	Day 7 from randomisation
Secondary	Clinical status on a seven-category ordinal scale (Day 14)	Clinical status of patients at given on the seven-category ordinal scale (see primary endpoint for scale)	Day 14 from randomisation
Secondary	Overall survival	Survival of patients to end of study	28 days from randomisation
Secondary	Time to improvement by two points on the NEWS score	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	Up to 28 days from randomisation
Secondary	Time to improvement by two points on the NEWS element score for temperature	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	Up to 28 days from randomisation
Secondary	Time to improvement by two points on the NEWS element score for heartrate	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	Up to 28 days from randomisation
Secondary	Time to improvement by two points on the NEWS element score for respiratory rate	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	Up to 28 days from randomisation
Secondary	Time to improvement by two points on the NEWS element score for oxygen saturation.	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	Up to 28 days from randomisation
Secondary	Admission to intensive care	Frequency of admission of patients to intensive care	Up to 28 days from randomisation
Secondary	Requirement for mechanical ventilation	Frequency of requirement to administer mechanical ventilation to patients	Up to 28 days from randomisation
Secondary	Requirement for non-invasive ventilation, continuous positive airways pressure or high-flow oxygen	Frequency of requirement to administer non-invasive ventilation, continuous positive airways pressure or high-flow oxygen to patients	Up to 28 days from randomisation
Secondary	Incidence of bacterial or fungal infection	Frequency of culture-confirmed bacterial or fungal infection in patients	Up to 28 days from randomisation
Secondary	Incidence of adverse events not directly caused by COVID-19 infection.	Frequency and severity of adverse events in patients not directly attributed by clinicians to COVID-19 infection.	Up to 28 days from randomisation.