meta|Evidence - COVID-19
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favipiravir (n=44) vs. favipiravir (n=45)
randomized controlled trial high risk of bias
immediate favipiravir
favipiravir administered orally between day 1 and day 10, 1800 mg twice a day on day 1 followed by 800 mg twice a day from day 2
delayed favipiravir
favipiravir administered orally between day 6 and day 15, 1800 mg twice a day on day 6 followed by 800 mg twice a day from day 7
COVID 19 all comers
asymptomatic and minimally symptomatic patientsRT-PCR test positive
open label
25 centres, japan
favipiravir (n=10) vs. standard of care (n=10)
randomized controlled trial some concerns about risk of bias
favipiravir
The first dose was 1600 mg or 2200mg orally, followed by 600 mg each time, three times a day, and the duration of administration was not more than 14 days
standard treatment
antiviral treatment included lopinavir/ritonavir (400 mg/100 mg, bid, po.) or darunavir/cobicistat (800 mg/150 mg, qd, po.) and arbidol (200 mg, tid, po.
3 arms: favipiravir (n=10), baloxavir marboxil (n=10), current antiviral treatment (n=10)
COVID 19 all comers
exclusion of considered as severe disease: has an ongoing respiratory deficiency and subjected to invasive mechanical ventilation; or presence of shock; or admitted to the ICU due to complications;
open-label, randomized
1 center, China
Time to clinical improvement was defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven category ordinal scale or live discharge from the hospital, whichever came first.
favipiravir (n=-9) vs. tocilizumab (n=-9)
randomized controlled trial some concerns about risk of bias
favipavir
Favipiravir: On the 1st day, 1600mg each time, twice a day; from the 2nd to the 7th day, 600mg each time, twice a day
tocilizumab
1 dose 4-8 mg/kg (max 400mg). 2nd dose within 24h if persistent fever
COVID 19 all comers
open label
10 centres, China
3 arms : Favipiravir Combined With Tocilizumab ; Favipiravir; Tocilizumab
favipiravir (n=120) vs. umifenovir (arbidol) (n=120)
randomized controlled trial some concerns about risk of bias
favipiravir
favipiravir tablets (1600 mg/time on the first day, twice a day; 600 mg/time from the second day to the end of the experiment, twice a day)
umifenovir
umifenovir (200 mg each time, 3 times a day, from the first day to the end of the trial)
COVID 19 all comers
double-blind
China, 3 hospitals
Clinical recovery was defined as continuous (>72 hours) recovery of body temperature, respiratory rate, oxygen saturation and cough relief after treatment
Some incorrectness in the paper (for example in the result table (table 2), it is not the rate ratio that is reported but the risk difference). Arise some concern about a selective reporting.
favipiravir (n=75) vs. standard of care (n=75)
randomized controlled trial some concerns about risk of bias
favipiravir
3,600 mg (1,800 mg BID) (Day 1) 1,600 mg (800 mg BID) (Day 2 or later) for up to maximum of 14 days
sandard of care
Drugs thought to have antiviral activity against SARS CoV2 (including hydroxychloroquine) were prohibited
COVID 19 hospitalized
open label
12 centres, India
Clinical cure was based on clinician assessment and defined as recovery of fever (axillary temperature ≤97.8°F), respiratory rate of ≤20 breaths/minute, oxygen saturation ≥98% without oxygen supplementation (which was later revised to align with the discharge criterion of ≥95% oxygen saturation issued by the Indian Ministry of Health prior to the start of the study), and cough relief (mild or no cough) maintained for ≥72 hours.
favipiravir (n=20) vs. standard of care (n=20)
randomized controlled trial some concerns about risk of bias
favipiravir
Favipiravir 1600 mg twice a day (BID) on Day 1 followed by 600 mg BID on Days 2-14 (1600/600 mg), or Favipiravir 1800 mg BID on Day 1 followed by 800 mg BID on Days 2-14 (1800/800 mg)
standard of care
COVID 19 hospitalized
open label
6 centres, Russia
adaptative phase II/III3 arms : favipiravir low dose, or favipiravir high dose or SOC
favipiravir (n=193) vs. lopinavir/ritonavir (n=187)
randomized controlled trial some concerns about risk of bias
favipiravir
Favipiravir 1600 mg stat and then 600 mg every 8 h plus hydroxychloroquine 200 mg twice a day for 1 week.
lopinavir/ritonavir
single dose of hydroxychloroquine 400 mg followed by 100 400 Lopinavir/Ritonavir twice a day for 1 week
Later on, during the trial (31 May 2020), in light of emerging evidence, daily hydroxychloroquine in the Favipiravir group was reduced to a single dose of 400 mg as in control group
COVID-19 mild to moderate
open-label
20 centres, Iran
favipiravir (n=175) vs. placebo (n=178)
randomized controlled trial high risk of bias
favipiravir
1,800 mg BID on Day 1 800 mg BID for next 9 days (maximum)
placebo
COVID-19 mild to moderate
double blind
20 centres, Kuwait
favipiravir (n=75) vs. placebo (n=74)
randomized controlled trial risk of bias NA
Favipiravir
Favipiravir administered orally, 1800 mg on the first dose (day 1) followed by 800 mg twice daily for the next 9 days (days 2-10).
placebo
COVID-19 mild to moderate
double blind
USA
favipiravir (n=107) vs. placebo (n=49)
randomized controlled trial some concerns about risk of bias
Favipiravir
1800 mg twice a day on Day 1, followed by 800 mg twice a day for up to 13 days.
placebo
1:2 ratio. Seven patients in the placebo group were switched to treatment with favipiravir during Days 2–8 due to a lack of efficacy.
COVID-19 mild to moderate
Single blind.
Japan
Improvement was defined as follows:(1) improvement in temperature was defined as axillary temperature falling to =< 37.4 C and remaining at =< 37.4 C for at least 24 h (temperature recordings taken within 4 h after use ofan antipyretic were excluded); (2) improvement in SpO2 was defined as SpO2 remaining >= 96%for at least 24 h without the use of oxygen therapy; (3) improvement on chest imaging was defined as improvement in chest imaging findings taken at least 24 h after the previous image judged to be the worst; and (4) recovery to SARS-CoV-2-negative was defined as two consecutive negative results on qualitative tests by nucleic acid amplification separated by at least 24 h.
favipiravir (n=50) vs. standard of care (n=50)
randomized controlled trial some concerns about risk of bias
favipiravir
3200 mg (1600 mg 12 hourly) loading dose on day-1 followed by 1200 mg maintenance dose (600 mg 12 hourly daily) on day-2 to day-10
standard of care
oseltamivir 75 mg 12 hourly for 5-10 days and hydroxychloroquine 400mg 12 hourly day -1 followed by 200mg 12 hourly daily on day- 2 to day-5-10
COVID-19 mild to moderate
open label, randomized
2 centres, Egypt
favipiravir (n=100) vs. standard of care (n=100)
randomized controlled trial some concerns about risk of bias
favipiravir
1600 mg 2 times a day; on days 2-14 of treatment - 600 mg 2 times a day
standard of care
COVID-19 mild to moderate
open label
5 centres, Russia
Rate of clinical status improvement by categorical ordinal scale of clinical status improvement by 2 or more categories by Day 10 WHO Ordinal Scale for Clinical Improvement (WHO-OSCI), 0 - uninfected (There are no clinical and virological signs of infection), 8 - dead, higher scores mean a worse outcome
Article published in Russian. Results extracted from clinicaltrials.gov.
favipiravir (n=125) vs. standard of care (n=129)
randomized controlled trial some concerns about risk of bias
Favipiravir and Hydroxychloroquine
Favipiravir: 1800 mg twice daily for one day, followed by 800mg (total days of therapy is 10 days or till hospital discharge)Hydroxychloroquine (400mg) twice daily on day 1; for days 2-5 (200mg) twice daily.
standard of care
COVID-19 mild to moderate
open label
9 centers, Saudi Arabia
Moderate or Severe confirmed COVID-19
Trial stopped for futility after the first interim analysis
favipiravir (n=112) vs. standard of care (n=56)
randomized controlled trial some concerns about risk of bias
favipiravir
1800 mg BID on day 1, followed by 800 mg BID for up to9 days)
standard of care
umifenovir intranasal interferon alpha-2b, orhydroxychloroquine) for up to 10 days
COVID-19 mild to moderate
open label
10 centres, Russia
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