ABSTRACT
Background: No antiviral drug has been proven effective for the treatment of patients with moderate-to-severe coronavirus disease 2019 (COVID-19). Favipiravir and hydroxychloroquine were introduced as potential antiviral agents to treat patients with COVID-19.Methods: We conducted an investigator-initiated, multicentre, open-label, randomised trial involving hospitalised patients with confirmed moderate-to-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at nine hospitals in Saudi Arabia. Eligible patients were adult with moderate-to-severe COVID-19 defined as oxygen saturation (Sao2) of 94% or less while breathing ambient air or significant clinical symptoms with chest X-ray changes requiring hospital admission. Randomisation was in a 1:1 ratio to receive standard care (control group) or standard care plus favipiravir and hydroxychloroquine. The favipiravir loading dose was 1800 mg twice daily on day 1, then 800mg twice daily for nine days and hydroxychloroquine as 400mg twice daily, followed by 200mg twice daily for days 2-5. The primary outcome was time to clinical improvement of two points (from the status at randomisation) on a seven-category ordinal scale or live discharge from the hospital within 14 days. Analyses were done in an intention-to-treat population of patients to assess the primary and secondary endpoints. The trial is registered at ClinicalTrials.gov (NCT04392973).Findings: From May 2020 to Jan 2021, 254 patients were enrolled; 129 were assigned to standard of care and 125 patients to the combination of favipiravir and hydroxychloroquine. The mean age was 52·65 ±13·06 years, 59·4% were men, and 229 (90·15%) required supplemental oxygen at randomisation (with or without non-invasive ventilation). The time to clinical improvement was not significantly different between the two groups; median of 9 days (95%CI: 8, 12) in the treatment group and 7 days (95%CI: 6, 10) in the control group (HR:0·845; 95% CI 0·617 to 1·157; p-value = 0·29). The median duration of hospitalisation among patients discharged on or before day 14 was 9 days (95%CI: 8, 12) for the treatment group and 8 days (95%CI: 7, 10) for the control group with a p-value of 0·42. The 28-day mortality was not significantly different between the two groups, 9 (7·63%) in the treatment group vs 13 (10·32%) in the control group; p-value=0·45. The most prevalent adverse events were headache, elevation in ALT, and the prolonged QTc interval in the treatment group.Interpretation: The combination of favipiravir and hydroxychloroquine did not result in a statistically significant clinical benefit in patients with moderate-to-severe COVID-19. No new safety signals were recognised for both medications.Trial Registration: This trial is registered with ClinicalTrials.gov, Identifier: NCT04392973, May 19, 2020.Funding Statement: King Abdullah International Medical Research Center, Saudi Arabia.Declaration of Interests: All authors declare no competing interests.Ethics Approval Statement: This trial was approved by the Saudi Food and Drug Authority (SFDA). Ethical approval was obtained from the Institutional Review Board (IRB) at the Ministry of National Guard-Health Affairs (MNGHA) and Ministry of Health (MOH). The trial was overseen by an independent data and safety monitoring board (DSMB). The trial was done according to the Declaration of Helsinki principles and the International Conference on Harmonization-Good Clinical Practice guidelines.
Subject(s)
COVID-19 , Coronavirus InfectionsABSTRACT
BackgroundThe Saudi Vision 2030 project recognized the integral role of health research in transforming, modernizing and governing the healthcare system, as well as improving health. The nature of health research prioritization is context-specific, and there is an obligation to effectively allocate resources to initiatives that will achieve the greatest impact, which is discussed in this paper.MethodsThe best practice for health research prioritization depends on the existing needs and context. The e-Delphi technique was conducted via an online self-administered questionnaire that covered health research topics, topics related to Vision 2030, as well as collaborative research. Criteria used for scoring the selected topics were: appropriateness, relevance, feasibility, urgency, collaboration and impact of research outcome. Research domains were prioritized by ranking the weighted mean aggregate score and all topics of the top five ranked domains, along with the aggregate scores of the answers of those in leadership positions were pooled together, validated, verified, summarized, refined and then classified into themes. ResultsThe participants included those from a full range of health specialties and subspecialties (46.5% physicians, 39% health specialists, 10% pharmacists and 3.6% dentists), and the study achieved balanced regional participation and covered a wide spectrum of qualification and professional levels. In total there were 2252 participants and 98% belonged to MoH. Of those from the MoH, 134 were leaders (85 Headquarters policy makers and 49 regional decision makers), while the rest were made up from individuals from 16 Health Affairs Directorates spanning 75 hospitals and specialized health centers, 24 primary health care centers , 2 healthcare clusters, in addition to five medical cities. Community involvement was represented by 26 organizations. Approximately half of stakeholders contributed to scientific research, while 24% had previous publications, and only 6% had a direct influence in health policymaking. The study deliverables were listed into three agendas:1. Health System Research Priority Themes: Service Delivery, Workforce, Information Systems, Access to Essential Medicines, Financing, Governance & Leadership and Disaster Response. 2. Diseases and Health Problems Themes: Non-Communicable and Communicable Diseases, Trauma, Public Health, Dental Health, Environmental Health, Pilgrims’ Health, Women’s Health, Child & Geriatric Health, Biomedical Technology, Radiology and Physical Technology.3. National and International Collaborative Research Themes: Major research areas impacted by COVID-19, Public Health, Healthcare Access, Medical Care & Universal Health Coverage, Value-based Healthcare, Health System Financing and Economics, Health Information and Communication Technology, Health System Governance, Health Workforce Development and Health System Preparedness and Response to Emergency.Conclusion Adequate description of the stakeholders and the methodology can strengthen legitimacy, credibility and maximize the impact of the priority setting process. Involvement of policymakers, researchers and funding organizations increases the opportunity of translation into actual research, supports redesigning the research landscape and ensures uptake of results and integration.