Dataset Information

Efficacy and Safety of Favipiravir in Moderate COVID-19 Pneumonia Patients without Oxygen Therapy: A Randomized, Phase III Clinical Trial.

ABSTRACT:

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is an enveloped, single-stranded RNA virus. Favipiravir is an orally administrable antiviral drug whose mechanism of action is to selectively inhibit RNA-dependent RNA polymerase. A preliminary trial in COVID-19 patients reported significant improvements across a multitude of clinical parameters, but these findings have not been confirmed in an adequate well-controlled trial. We conducted a randomized, single-blind, placebo-controlled Phase III trial assessing the efficacy and safety of favipiravir in patients with moderate pneumonia not requiring oxygen therapy.

Methods

COVID-19 patients with moderate pneumonia (SpO₂ ≥ 94%) within 10 days of onset of fever (temperature ≥ 37.5 °C) were assigned to receive either placebo or favipiravir (1800 mg twice a day on Day 1, followed by 800 mg twice a day for up to 13 days) in a ratio of 1:2. An adaptive design was used to re-estimate the sample size. The primary endpoint was a composite outcome defined as the time to improvement in temperature, oxygen saturation levels (SpO₂), and findings on chest imaging, and recovery to SARS-CoV-2-negative. This endpoint was re-examined by the Central Committee under blinded conditions.

Results

A total of 156 patients were randomized. The median time of the primary endpoint was 11.9 days in the favipiravir group and 14.7 days in the placebo group, with a significant difference (p = 0.0136). Favipiravir-treated patients with known risk factors such as obesity or coexisting conditions provided better effects. Furthermore, patients with early-onset in the favipiravir group showed higher odds ratio. No deaths were documented. Although adverse events in the favipiravir group were predominantly transient, the incidence was significantly higher.

Conclusions

The results suggested favipiravir may be one of options for moderate COVID-19 pneumonia treatment. However, the risk of adverse events, including hyperuricemia, should be carefully considered.

Trial registration

Clinicaltrials.jp number: JapicCTI-205238.

SUBMITTER: Shinkai M

PROVIDER: S-EPMC8396144 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

Efficacy and Safety of Favipiravir in Moderate COVID-19 Pneumonia Patients without Oxygen Therapy: A Randomized, Phase III Clinical Trial.

Shinkai Masaharu M Tsushima Kenji K Tanaka Shingo S Hagiwara Eri E Tarumoto Norihito N Kawada Ichiro I Hirai Yuji Y Fujiwara Sho S Komase Yuko Y Saraya Takeshi T Koh Hidefumi H Kagiyama Naho N Shimada Megumi M Kanou Daiki D Antoku Shinichi S Uchida Yujiro Y Tokue Yutaka Y Takamori Mikio M Gon Yasuhiro Y Ie Kenya K Yamazaki Yoshitaka Y Harada Kazumasa K Miyao Naoki N Naka Takashi T Iwata Mitsunaga M Nakagawa Atsushi A Hiyama Kazutoshi K Ogawa Yoshihiko Y Shinoda Masahiro M Ota Shinichiro S Hirouchi Takatomo T Terada Jiro J Kawano Shuichi S Ogura Takashi T Sakurai Tsutomu T Matsumoto Yoshihiko Y Kunishima Hiroyuki H Kobayashi Osamu O Iwata Satoshi S

Infectious diseases and therapy 20210827 4

<h4>Introduction</h4>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is an enveloped, single-stranded RNA virus. Favipiravir is an orally administrable antiviral drug whose mechanism of action is to selectively inhibit RNA-dependent RNA polymerase. A preliminary trial in COVID-19 patients reported significant improvements across a multitude of clinical parameters, but these findings have not been confirmed in an adequate well-contro ...[more]

PMID: 34453234

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Project description:BackgroundThe effectiveness of combination therapy for COVID-19 pneumonia remains unclear. We evaluated favipiravir, camostat, and ciclesonide combination therapy in patients with moderate COVID-19 pneumonia.MethodsIn this open-label phase 3 study, hospitalized adults who were positive for SARS-CoV-2 and had COVID-19 pneumonia were enrolled prior to official vaccination drive in Japan. Participants were randomly assigned to favipiravir monotherapy or favipiravir + camostat + ciclesonide combination therapy. The primary outcome was the length of hospitalization due to COVID-19 infection after study treatment. The hospitalization period was calculated from the time of admission to the time of patient discharge using the clinical management guide of COVID-19 for front-line healthcare workers developed by the Japanese Ministry of Health, Labour, and Welfare (Version 3). Cases were registered between November 11, 2020, and May 31, 2021. Japan Registry of Clinical Trials registration: jRCTs031200196.FindingsOf 121 enrolled patients, 56 received monotherapy and 61 received combination therapy. Baseline characteristics were balanced between the groups. The median time of hospitalization was 10 days for the combination and 11 days for the monotherapy group. The median time to discharge was statistically significantly lower in the combination therapy vs monotherapy group (HR, 1·67 (95% CI 1·03-2·7; P = 0·035). The hospital discharge rate was statistically significantly higher in the combination therapy vs monotherapy group in patients with less severe COVID-19 infections and those who were ≤60 years. There were no significant differences in clinical findings between the groups at 4, 8, 11, 15, and 29 days. Adverse events were comparable between the groups. There were two deaths, with one in each group.InterpretationCombination oral favipiravir, camostat and, ciclesonide therapy could decrease the length of hospitalization stays without safety concerns in patients with moderate COVID-19 pneumonia. However, lack of hard clinical primary outcome is one of the major limitations of the study.FundingThis research was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 20fk0108261h0001.

Project description:BackgroundIn 2019, a highly pathogenic coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surfaced and resulted in the outbreak of coronavirus disease 2019 (COVID-19). With the aim of finding effective drugs to fight against the disease, several trials have been conducted since COVID-19 can only be considered a treatable disease, from a clinical point of view, after the availability of specific and effective antivirals. AZVUDINE (FNC), initially developed for treating HIV, is a potential treatment for COVID-19 as it has the capability to lower the patient's viral load and promote recovery.MethodsVolunteers infected with SARS-CoV-2 confirmed by reverse transcription polymerase chain reaction (RT-PCR), with good kidney and liver function, who were not using other antivirals or monoclonal antibodies were eligible. Samples from patients were assessed for viral load every 48 h during treatment using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and droplet digital polymerase chain reaction (ddPCR).ResultsThe study's primary outcome measure was the percentage of participants showing an improvement in clinical scores, while the secondary outcome measure was the percentage of participants with a clinical outcome of cure. These measures were used to assess the safety and efficacy of FNC for treating COVID-19. In the analysis of sociodemographic variables, no significant differences were detected between patients in the FNC and the placebo group for race, age group, or sex. The results showed a potential benefit to participants who received FNC during the study, as observed in the shorter hospital stay, shorter negative conversion time of SARS-CoV-2, and a significant reduction in viral load. Furthermore, the reduction in fever and chills were significant at D1, D2, and D3. In this study, a total of 112 adverse events cases were noted, with 105 cases being categorized as non-serious and only 7 cases as serious adverse events.ConclusionThe pandemic is not being effectively controlled and is causing multiple waves of infection that require extensive medical resources. However, FNC has demonstrated potential to reduce the treatment duration of moderate COVID-19 cases, thereby saving significant medical resources. This makes FNC a promising candidate for COVID-19 treatment.Clinical trial registration: [clinicaltrials.gov], identifier [NCT04668235].

Dataset Information

Efficacy and Safety of Favipiravir in Moderate COVID-19 Pneumonia Patients without Oxygen Therapy: A Randomized, Phase III Clinical Trial.

Introduction

Methods

Results

Conclusions

Trial registration

Publications

Efficacy and Safety of Favipiravir in Moderate COVID-19 Pneumonia Patients without Oxygen Therapy: A Randomized, Phase III Clinical Trial.

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