Clinical Trial Results:
Safety and Efficacy of Favipiravir in COVID-19 Patients with Pneumonia −A randomized, double blind, placebo- controlled study −
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Summary
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EudraCT number |
2020-002753-22 |
Trial protocol |
ES |
Global end of trial date |
05 Oct 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Sep 2022
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First version publication date |
15 Sep 2022
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Other versions |
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Summary report(s) |
Sinopsis |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
FAVID-01-20-SP
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Ferrer Internacional, S.A.
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Sponsor organisation address |
Diagonal 549, Barcelona, Spain, 08029
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Public contact |
Rebeca Aldonza Aguayo, Ferrer Internacional, S.A., +34 662 213 660, raldonza@ferrer.com
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Scientific contact |
Rebeca Aldonza Aguayo, Ferrer Internacional, S.A., +34 662 213 660, raldonza@ferrer.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
05 Oct 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
05 Oct 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
05 Oct 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The overall objective of the study is to evaluate the clinical safety and potential efficacy of favipiravir relative to the control arm in patients hospitalized with COVID-19
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Protection of trial subjects |
The study was conducted in compliance with the protocol, regulatory requirements, data protection laws, good clinical practice (GCP) and the ethical principles of the Declaration of Helsinki as adopted by the World Medical Assembly, 1964 (and subsequent revisions). Before the first patient was enrolled in the study, all ethical, regulatory, and legal requirements were met. The study was not started until approval by the ethics committee and other pertinent authorities has been obtained. By signing the protocol, the investigator agreed to adhere to the instructions and procedures described in the protocol and by so doing to follow the principles of good clinical practice they entail.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
01 Sep 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 44
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Worldwide total number of subjects |
44
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EEA total number of subjects |
44
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
43
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
Forty-six patients signed the ICF and were assessed for eligibility. There were no screening failures. The included patients (n=46) were randomized 1:1 in the study as follows: 24 patients were randomized to favipiravir and 22 to placebo. A total of 8 patients discontinued the study prematurely: 5 patients from favipiravir group and 3 from placebo. | ||||||||||||||||||||||||
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Pre-assignment
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Screening details |
All patients provided written informed consent to participate in the study prior to being screened. The planned target of patients was 100 patients. Finally, 46 patients were screened and 44 included. | ||||||||||||||||||||||||
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Period 1
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Period 1 title |
Observation/Examination Period (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor | ||||||||||||||||||||||||
Blinding implementation details |
The randomization list was not available to the investigator, study staff, patients, sponsor, or monitor. CRO made randomization envelopes. Treatment codes had not to be broken except in emergency situations and, if possible, the sponsor had to be contacted before the emergency code was opened. At the end of the study, the unused emergency code labels were checked and a statement to the effect that all were intact (or not as the case may be) was made on the database lock form.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Favipiravir | ||||||||||||||||||||||||
Arm description |
1800 mg (9 pills) × 2 times/day × 1 day + 800 mg (4 pills) × 2 times/day × 9 days (10 days). And existing treatment for COVID-19 according to the current clinical practice for each participating site, except for prohibited medications in this protocol; Symptomatic treatment including tocilizumab and corticosteroids according to the clinical assessment by the investigator. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Favipiravir
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Investigational medicinal product code |
T-705a
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Dosage form: tablet (one tablet contains 200mg of favipiravir). Orally administered twice on Day 1, and then 800 mg daily on Day 2 and thereafter for up to 9 days
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Arm title
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Placebo | ||||||||||||||||||||||||
Arm description |
Favipiravir matching placebo. And existing treatment for COVID-19 according to the current clinical practice for each participating site, except for prohibited medications in this protocol. Symptomatic treatment including Tocilizumab and corticosteroids according to the clinical assessment by the investigator | ||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1800 mg (9 pills) × 2 times/day × 1 day + 800 mg (4 pills) × 2 times/day × 9 days (10 days)
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Baseline characteristics reporting groups
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Reporting group title |
Favipiravir
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Reporting group description |
1800 mg (9 pills) × 2 times/day × 1 day + 800 mg (4 pills) × 2 times/day × 9 days (10 days). And existing treatment for COVID-19 according to the current clinical practice for each participating site, except for prohibited medications in this protocol; Symptomatic treatment including tocilizumab and corticosteroids according to the clinical assessment by the investigator. | ||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Favipiravir matching placebo. And existing treatment for COVID-19 according to the current clinical practice for each participating site, except for prohibited medications in this protocol. Symptomatic treatment including Tocilizumab and corticosteroids according to the clinical assessment by the investigator | ||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Favipiravir
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Reporting group description |
1800 mg (9 pills) × 2 times/day × 1 day + 800 mg (4 pills) × 2 times/day × 9 days (10 days). And existing treatment for COVID-19 according to the current clinical practice for each participating site, except for prohibited medications in this protocol; Symptomatic treatment including tocilizumab and corticosteroids according to the clinical assessment by the investigator. | ||
Reporting group title |
Placebo
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Reporting group description |
Favipiravir matching placebo. And existing treatment for COVID-19 according to the current clinical practice for each participating site, except for prohibited medications in this protocol. Symptomatic treatment including Tocilizumab and corticosteroids according to the clinical assessment by the investigator | ||
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End point title |
Primary endpoint: Time to clinical improvement | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
28 days
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Statistical analysis title |
Time to clinical improvement by treatment group | ||||||||||||
Statistical analysis description |
The primary treatment comparison has been evaluated using a two-sided significance level of 0.05. The functions used for the hypothesis contrast and plotting the survival curves were the survfit() and ggsurvplot() functions from the {survival} and {survminer} packages respectively from the R statistical software
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Comparison groups |
Favipiravir v Placebo
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Number of subjects included in analysis |
44
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.05 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
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End point title |
Secondary endpoint: WHO ordinal scale displacement analysis | ||||||||||||
End point description |
WHO score mean change
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End point type |
Secondary
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End point timeframe |
from baseline to Day 28
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Secondary: Time to fever resolution | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
from baseline to Day 28
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| No statistical analyses for this end point | ||||||||||
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End point title |
secondary: National Early Warning Score (NEWS) | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
from baseline to Day 28
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| No statistical analyses for this end point | ||||||||||
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End point title |
Secondary: time to weaning from mechanical ventilation | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
from baseline to Day 28
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| No statistical analyses for this end point | ||||||||||
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End point title |
Secondary: Time to hospital discharge | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
from baseline to Day 28
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| No statistical analyses for this end point | ||||||||||
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End point title |
Secondary: Mortality up to 28 (incidence) | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
from baseline to Day 28
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| No statistical analyses for this end point | ||||||||||
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End point title |
Secondary: Time until weaning from oxygen therapy | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
from baseline to Day 28
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| No statistical analyses for this end point | ||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events were recorded beginning immediately after the ICF was signed. The investigator (and/or designee) documented all AEs reported by the subject from the ICF signing to completion of the final follow-up.
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Adverse event reporting additional description |
Any subject who is withdrawn from the study due to an AE shall be followed until the outcome of the event is determined, and the investigator will document available follow-up information on the subject’s database.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.0
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Reporting groups
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Reporting group title |
Favipiravir
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Reporting group description |
1800 mg (9 pills) × 2 times/day × 1 day + 800 mg (4 pills) × 2 times/day × 9 days (10 days). And existing treatment for COVID-19 according to the current clinical practice for each participating site, except for prohibited medications in this protocol; Symptomatic treatment including tocilizumab and corticosteroids according to the clinical assessment by the investigator. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Favipiravir matching placebo. And existing treatment for COVID-19 according to the current clinical practice for each participating site, except for prohibited medications in this protocol. Symptomatic treatment including Tocilizumab and corticosteroids according to the clinical assessment by the investigator | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0.1% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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05 Nov 2020 |
Include an inclusion criterion (influenza test) and an exclusion criterion (patients on the current treatment with remdesevir or who have been treated with remdesevir during last 7 days before inclusion) and their rationales, change the evaluation of clinical findings from twice daily to once daily, update the study period, update key contacts and add a footnote with the protocol version. |
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08 Feb 2021 |
The person responsible for signing the protocol from the sponsor side has been changed. Some inclusion and exclusion criteria have been modified, some secondary and additional endpoints have been changed to be adapted to the current clinical practice, study period has been updated, study schedule has been modified and the section of statistical methods has been changed to be better defined and to include the estimands |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
