Early treatment of Favipiravir in COVID-19 patients without pneumonia: a multicentre, open-labelled, randomized control study

Sirijatuphat, Rujipas; Manosuthi, Weerawat; Niyomnaitham, Suvimol; Owen, Andrew; Copeland, Katherine Kradangna; Charoenpong, Lantharita; Rattanasompattikul, Manoch; Mahasirimongkol, Surakameth; Wichukchinda, Nuanjun; Chokephaibulkit, Kulkanya

doi:10.1080/22221751.2022.2117092

Cited by 21 publications

(20 citation statements)

References 49 publications

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“…The strengths of the HI strategy were: (1) the establishment of timely and effective interactions between patients and healthcare professionals, (2) the creation of a good standard of holistic care, and (3) the prompt delivery of needed antiviral drugs to infected patients. Previous meta-analysis [42] and our data from the current investigation [30,43] demonstrate that early access to medical treatment resulted in significant clinical improvements and improved survival rates. Conducting quarantine and isolation at home rather than in a hospital or "hospitel" has fewer mental health consequences because patients are confined to a familiar environment.…”

Section: Supporting Systemmentioning

confidence: 52%

“…Favipiravir was the recommended anti-viral therapy, especially in patients at high risk for COVID-19 pneumonia within 48 h, and was given for 5 days, but the duration could be extended to as long as 14 days based on the patient's clinical severity. The dose was 1800 mg twice daily on the first day followed by 800 mg twice daily [30].…”

Section: Establishing Home Isolation Using the Find-test-trace-isolat...mentioning

confidence: 99%

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Home Isolation and Online Support Strategies during Mild COVID-19 Pandemic Waves in Thailand: A Scoping Review

Pinsawas

Ophakas

Bedavanija

et al. 2023

COVID

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Objectives: In 2021, Thailand experienced its fourth and fifth waves of COVID-19, overwhelming the nation’s public health system. The significant gap between health resources and the demand for services from patients was one of the primary challenges in responding to the catastrophic COVID-19 pandemic. Hospitals were inundated with a surge in new patients, leading to a growing backlog of individuals suffering delayed care or even rejection from the healthcare system. To tackle this issue, strategies such as “outpatient self-isolation” (SI), “home-based isolation” (HI), and “community-based isolation” (CI) were implemented to stabilize COVID-19 cases with mild to moderate symptoms. This review aimed to explore the experiences in the management of COVID-19 care in patients with mild to moderate symptoms and identify challenges after the initial response of the Thailand health system to the pandemic. Methods: This study was conducted during the Delta pandemic (June–November 2021) and the Omicron pandemic (December 2021–15 March 2022). We present the lessons learned from the management of the HI system based on experiences gained at a university hospital, which provided remote professional-to-patient support during the pandemic. The study involved retrospective data from electronic medical records and qualitative analysis of responses provided during the pandemic using the HI system. Results: Data from a total of 2704 and 1912 participants were included in the analysis. The vast majority of patients were assigned to HI immediately after being diagnosed with COVID-19. This system facilitated remote consultations, provision of necessary medications, and delivery of survival kits to patients’ homes. Qualitative reviews indicated several key factors that could contribute to successful COVID-19 management under the HI system: (1) effective management and vaccine status, (2) establishment of home isolation using the find-test-trace-isolate-support system, and (3) adherence to home isolation guidelines and system support. Challenges included the digitalization of tools for securing isolation, team preparedness and adequate support system during HI, as well as hospital policies for psychological support for healthcare workers and measures to alleviate their workload. Conclusions: Our investigation suggests that the HI teleconsultation system was an effective approach to managing COVID-19. It allowed for a prompt response to patients’ needs and provided timely access to medical support, particularly for individuals with mild to moderate symptoms.

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Section: Supporting Systemmentioning

confidence: 52%

Section: Establishing Home Isolation Using the Find-test-trace-isolat...mentioning

confidence: 99%

Home Isolation and Online Support Strategies during Mild COVID-19 Pandemic Waves in Thailand: A Scoping Review

Pinsawas

Ophakas

Bedavanija

et al. 2023

COVID

View full text Add to dashboard Cite

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“…Nor has it shown any impact on time to clinical improvement in moderate symptomatic COVID-19 disease [21,22] . Other trials comparing with a no-treatment arm [23] have also shown no bene t from favipiravir. In a recent trial, favipiravir did not improve clinical outcomes in all patients admitted to hospital with COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Safety and Efficacy of Favipiravir in COVID-19 Patients with Pneumonia. A randomized, double-blind, placebo-controlled study (FAVID)

Horcajada,

Aldonza,

Real

et al. 2023

Preprint

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Purpose: To design a randomized clinical trial to assess the efficacy and safety of favipiravir in patients with COVID-19 disease with pneumonia. Methods: A randomized, double blind, placebo-controlled clinical trial of favipiravir in patients with COVID-19 pneumonia was conducted in 3 Spanish sites. Randomization 1:1 to favipiravir or placebo (in both groups added to the Standard of Care) was performed to treat the patients with COVID-19 pneumonia. The primary endpoint was “time to clinical improvement,” measured as an improvement for ≥ two categories on a 7-point WHO ordinal scale in an up to 28 days' time frame. Results: 44 patients were randomized (23 in the favipiravir group and 21 in the placebo group). The median time to clinical improvement was not different between the favipiravir and the placebo arms (10 days for both groups) and none of the secondary endpoints showed significant differences between arms. The proportion of adverse events (both serious and non-serious) was statistically different between the favipiravir group (68.29%) and the placebo group (31.7%) (p = 0.019), but there was insufficient statistical evidence to correlate the degree of severity of the events with the treatment groups. Conclusions: Favipiravir administered for ten days to patients with COVID-19 and pneumonia did not improve outcomes compared with placebo. Although this is an underpowered negative study, efficacy results align with other randomized trials. However, in the present study, the non-serious adverse events were more frequent in the favipiravir group.

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“…The contribution of the cofactor-ligand electrostatic interaction to the total protein-ligand binding is almost twice as high as the sum of the steric and hydrogen bond contributions. Such a strong direct binding of FVP-RTP to the active site and cofactor suggests a possible alternative mechanism of FVP action, which may explain the scattering of the results of clinical trials [25,63] or the synergistic effect observed in combined treatment against SARS-CoV-2 [64].…”

Section: Binding Mode Of Biologically Active Formmentioning

confidence: 99%

“…FPV therapy with safe oral doses is effective for the treatment of outpatients with mild to moderate COVID-19 infection. Moreover, results regarding viral load reduction and an improvement in the radiological and clinical outcomes in COVID-19 patients are remarkable [24,25]. FPV is a very promising drug due to its mechanism of action, preclinical results, high degree of safety in humans, bioavailability, good treatment progress, and manufacturing reliability.…”

Section: Introductionmentioning

confidence: 99%

Elucidating the Role of Noncovalent Interactions in Favipiravir, a Drug Active against Various Human RNA Viruses; a 1H-14N NQDR/Periodic DFT/QTAIM/RDS/3D Hirshfeld Surfaces Combined Study

Latosińska

Seliger

et al. 2023

Molecules

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Favipiravir (6-fluoro-3-hydroxypyrazine-2-carboxamide, FPV), an active pharmaceutical component of the drug discovered and registered in March 2014 in Japan under the name Avigan, with an indication for pandemic influenza, has been studied. The study of this compound was prompted by the idea that effective processes of recognition and binding of FPV to the nucleic acid are affected predominantly by the propensity to form intra- and intermolecular interactions. Three nuclear quadrupole resonance experimental techniques, namely 1H-14N cross-relaxation, multiple frequency sweeps, and two-frequency irradiation, followed by solid-state computational modelling (density functional theory supplemented by the quantum theory of atoms in molecules, 3D Hirshfeld Surfaces, and reduced density gradient) approaches were applied. The complete NQR spectrum consisting of nine lines indicating the presence of three chemically inequivalent nitrogen sites in the FPV molecule was detected, and the assignment of lines to particular sites was performed. The description of the nearest vicinity of all three nitrogen atoms was used to characterize the nature of the intermolecular interactions from the perspective of the local single atoms and to draw some conclusions on the nature of the interactions required for effective recognition and binding. The propensity to form the electrostatic N−H···O, N−H···N, and C−H···O intermolecular hydrogen bonds competitive with two intramolecular hydrogen bonds, strong O−H···O and very weak N−H···N, closing the 5-member ring and stiffening the structure, as well as π···π and F···F dispersive interactions, were analysed in detail. The hypothesis regarding the similarity of the interaction pattern in the solid and the RNA template was verified. It was discovered that the -NH2 group in the crystal participates in intermolecular hydrogen bonds N–H···N and N–H···O, in the precatalytic state only in N–H···O, while in the active state in N–H···N and N–H···O hydrogen bonds, which is of importance to link FVP to the RNA template. Our study elucidates the binding modes of FVP (in crystal, precatalytic, and active forms) in detail and should guide the design of more potent analogues targeting SARS-CoV-2. Strong direct binding of FVP-RTP to both the active site and cofactor discovered by us suggests a possible alternative, allosteric mechanism of FVP action, which may explain the scattering of the results of clinical trials or the synergistic effect observed in combined treatment against SARS-CoV-2.

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Early treatment of Favipiravir in COVID-19 patients without pneumonia: a multicentre, open-labelled, randomized control study

Cited by 21 publications

References 49 publications

Home Isolation and Online Support Strategies during Mild COVID-19 Pandemic Waves in Thailand: A Scoping Review

Home Isolation and Online Support Strategies during Mild COVID-19 Pandemic Waves in Thailand: A Scoping Review

Safety and Efficacy of Favipiravir in COVID-19 Patients with Pneumonia. A randomized, double-blind, placebo-controlled study (FAVID)

Elucidating the Role of Noncovalent Interactions in Favipiravir, a Drug Active against Various Human RNA Viruses; a 1H-14N NQDR/Periodic DFT/QTAIM/RDS/3D Hirshfeld Surfaces Combined Study

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