Yuichiro Shindo1, Yasuhiro Kondoh2, Akiko Kada3, Yohei Doi4, Keisuke Tomii5, Hiroshi Mukae6, Naohiko Murata7, Ryosuke Imai8, Masaki Okamoto9, Yasuhiko Yamano2, Yasunari Miyazaki10, Masahiro Shinoda11, Hiromichi Aso12, Shinyu Izumi13, Haruyuki Ishii14, Ryota Ito4, Akiko M Saito3, Toshiki I Saito3, Yoshinori Hasegawa15. 1. Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan. yshindo@med.nagoya-u.ac.jp. 2. Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan. 3. Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan. 4. Department of Infectious Diseases, Fujita Health University School of Medicine, Toyoake, Japan. 5. Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan. 6. Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan. 7. Department of Respiratory Medicine, Nagoya Daini Red Cross Hospital, Nagoya, Japan. 8. Department of Pulmonary Medicine, St. Luke's International Hospital, Tokyo, Japan. 9. Department of Respirology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan. 10. Department of Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan. 11. Department of Respiratory Medicine, Tokyo Shinagawa Hospital, Tokyo, Japan. 12. Department of Respiratory Medicine, Ichinomiya Municipal Hospital, Ichinomiya, Japan. 13. Department of Respiratory Medicine, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan. 14. Department of Respiratory Medicine, Kyorin University, Tokyo, Japan. 15. National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
Abstract
INTRODUCTION: The administration of systemic corticosteroids is a key strategy for improving COVID-19 outcomes. However, evidence is lacking on combination therapies of antiviral agents and systemic corticosteroids. The objective of this study was to investigate the efficacy and safety of the combination therapy of favipiravir and methylprednisolone in preventing respiratory failure progression in patients with COVID-19 and non-critical respiratory failure. METHODS: We conducted a multicenter, open-label, single-arm phase II study. The patients received favipiravir 3600 mg on the first day, followed by 1600 mg for a total of 10-14 days. Methylprednisolone was administered intravenously at 1 mg/ideal body weight (IBW)/day from days 1 to 5, followed by 0.5 mg/IBW/day from days 6 to 10 if clinically indicated. The primary endpoint was the proportion of patients requiring mechanical ventilation (MV) (including noninvasive positive pressure ventilation) or those who met the criteria for tracheal intubation within 14 days of the study treatment initiation (MVCTI-14). RESULTS: Sixty-nine patients were enrolled and underwent the study treatment. Of them, the MVCTI-14 proportion was 29.2% (90% confidence interval 20.1-39.9, p = 0.200). The proportion of patients who required MV or who died within 30 days was 26.2%, and 30-day mortality was 4.9%. The most significant risk factor for MVCTI-14 was a smoking history (odds ratio 4.1, 95% confidence interval 1.2-14.2). The most common grade 3-4 treatment-related adverse event was hyperglycemia, which was observed in 21.7%. CONCLUSION: The MVCTI-14 proportion did not reach a favorable level in the clinical trial setting with the threshold of 35%. However, the proportion of MV or death within 30 days was 26.6%, which might be close to the findings (28.1%) of the RECOVERY trial, which showed the efficacy of dexamethasone for patients with COVID-19 and non-critical respiratory failure. Further evaluation of this combination therapy is needed. CLINICAL TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) identifier jRCTs041200025.
INTRODUCTION: The administration of systemic corticosteroids is a key strategy for improving COVID-19 outcomes. However, evidence is lacking on combination therapies of antiviral agents and systemic corticosteroids. The objective of this study was to investigate the efficacy and safety of the combination therapy of favipiravir and methylprednisolone in preventing respiratory failure progression in patients with COVID-19 and non-critical respiratory failure. METHODS: We conducted a multicenter, open-label, single-arm phase II study. The patients received favipiravir 3600 mg on the first day, followed by 1600 mg for a total of 10-14 days. Methylprednisolone was administered intravenously at 1 mg/ideal body weight (IBW)/day from days 1 to 5, followed by 0.5 mg/IBW/day from days 6 to 10 if clinically indicated. The primary endpoint was the proportion of patients requiring mechanical ventilation (MV) (including noninvasive positive pressure ventilation) or those who met the criteria for tracheal intubation within 14 days of the study treatment initiation (MVCTI-14). RESULTS: Sixty-nine patients were enrolled and underwent the study treatment. Of them, the MVCTI-14 proportion was 29.2% (90% confidence interval 20.1-39.9, p = 0.200). The proportion of patients who required MV or who died within 30 days was 26.2%, and 30-day mortality was 4.9%. The most significant risk factor for MVCTI-14 was a smoking history (odds ratio 4.1, 95% confidence interval 1.2-14.2). The most common grade 3-4 treatment-related adverse event was hyperglycemia, which was observed in 21.7%. CONCLUSION: The MVCTI-14 proportion did not reach a favorable level in the clinical trial setting with the threshold of 35%. However, the proportion of MV or death within 30 days was 26.6%, which might be close to the findings (28.1%) of the RECOVERY trial, which showed the efficacy of dexamethasone for patients with COVID-19 and non-critical respiratory failure. Further evaluation of this combination therapy is needed. CLINICAL TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) identifier jRCTs041200025.
Authors: Sanjay H Chotirmall; Lindsay M Leither; Başak Çoruh; Louisa L Y Chan; Anthony M Joudi; Samuel M Brown; Benjamin D Singer; Nitin Seam Journal: Am J Respir Crit Care Med Date: 2021-06-15 Impact factor: 21.405
Authors: Rupert Waudby-West; Benjamin J Parcell; Colin N A Palmer; Samira Bell; James D Chalmers; Moneeza K Siddiqui Journal: Eur Respir J Date: 2021-07-20 Impact factor: 16.671
Authors: William Morgenlander; Stephanie Henson; Daniel Monaco; Athena Chen; Kirsten Littlefield; Evan M Bloch; Eric Fujimura; Ingo Ruczinski; Andrew R Crowley; Harini Natarajan; Savannah E Butler; Joshua A Weiner; Mamie Z Li; Tania S Bonny; Sarah E Benner; David Sullivan; Shmuel Shoham; Thomas C Quinn; Susan Eshleman; Arturo Casadevall; Andrew D Redd; Oliver Laeyendecker; Margaret E Ackerman; Andrew Pekosz; Stephen J Elledge; Matthew Robinson; Aaron A R Tobian; H Benjamin Larman Journal: medRxiv Date: 2020-12-18