Efficacy of Early Treatment With Favipiravir on Disease Progression Among High-Risk Patients With Coronavirus Disease 2019 (COVID-19): A Randomized, Open-Label Clinical Trial

Abstract

Background Role of favipiravir in preventing disease progression in COVID-19 remains uncertain. We aimed to determine its effect in preventing disease progression from non-hypoxia to hypoxia among high risk COVID-19 patients. Study design This was an open-label, randomized clinical trial conducted at 14 public hospitals across Malaysia from February to June 2021 among 500 symptomatic, RT-PCR confirmed COVID-19 patients, aged ≥50 years with ≥1 co-morbidity, and hospitalized within first 7 days of illness. Patients were randomized on 1:1 ratio to favipiravir plus standard care or standard care alone. Favipiravir was administered at 1800mg twice-daily on day 1 followed by 800mg twice-daily until day 5. The primary endpoint was rate of clinical progression from non-hypoxia to hypoxia. Secondary outcomes included rates of mechanical ventilation, intensive care unit (ICU) admission, and in-hospital mortality. Results Among 500 patients were randomized (mean age, 62.5 [SD 8.0] years; 258 women [51.6%]; and 251 [50.2%] had COVID-19 pneumonia), 487 (97.4%) patients completed the trial. Clinical progression to hypoxia occurred in 46 (18.4%) patients on favipiravir plus standard care and 37 (14.8%) on standard care alone (OR 1.30; 95%CI, 0.81-2.09; P=.28). All three pre-specified secondary end points were similar between both groups. Mechanical ventilation occurred in 6 (2.4%) vs 5 (2.0%) (OR 1.20; 95%CI, 0.36-4.23; P=.76), ICU admission in 13 (5.2%) vs 12 (4.8%) (OR 1.09; 95%CI, 0.48-2.47; P=.84), and in-hospital mortality in 5 (2.0%) vs 0 (OR 12.54; 95%CI, 0.76- 207.84; P=.08). Conclusions Among COVID-19 patients at high risk of disease progression, early treatment with oral favipiravir did not prevent their disease progression from non-hypoxia to hypoxia.

Favipiravir, lopinavir-ritonavir or combination therapy (FLARE): a randomised, double blind, 2x2 factorial placebo-controlled trial of early antiviral therapy in COVID-19

“…Some small, open-label studies have indicated benefits in terms of clinical outcomes [25][26][27][28] or viral shedding [13,26]. However, other studies have indicated no clinically important benefit [29,30], including when given in early disease [31]. These studies were open label with heterogenous populations often including hospitalised patients, where antiviral treatment is expected to be less effective.…”

Future of antivirals in COVID-19: The case of favipiravir

“…Our systematic literature search retrieved 1493 hits, of which 613 were unique. After screening, we included six randomized controlled trials ( Table 1 ) [1] , [2] , [3] , [4] , [5] , [6] , with a total of 1,669 patients with COVID-19. The meta-analysis of the included trials [1] , [2] , [3] , [4] , [5] , [6] revealed no significant difference in the odds of mortality with the use of favipiravir among patients with COVID-19, relative to non-use of favipiravir; the estimated effect though indicated increased mortality ( Figure 1 ; pooled odds ratio = 1.09; 95% confidence interval 0.76 to 1.56) but is without adequate evidence against the null hypothesis of ‘no significant difference,’ at the current sample size.…”

“…The meta-analysis of the included trials [1] , [2] , [3] , [4] , [5] , [6] revealed no significant difference in the odds of mortality with the use of favipiravir among patients with COVID-19, relative to non-use of favipiravir; the estimated effect though indicated increased mortality ( Figure 1 ; pooled odds ratio = 1.09; 95% confidence interval 0.76 to 1.56) but is without adequate evidence against the null hypothesis of ‘no significant difference,’ at the current sample size.…”

The outcomes of favipiravir exposure in pregnancy: a case series

“…A dose regiment of 1600 mg twice daily on day 1, followed by 600 mg twice daily for 4 days was recommended [ 5 , 6 ]. As subsequent clinical researches demonstrated that favipiravir was not superior to standard supportive care in terms of reducing COVID-19 related hospitalization rates or mortality, favipiravir was dropped from the COVID-19 Guideline for Management of Adult Patients on revision dated 20 December 2021 [ 7 – 9 ]. It was also noted that the drug could be used when the treating physician deems necessary, as some of the clinical researches reported reduced duration of symptoms [ 7 , 10 ].…”