TY - JOUR
T1 - Phase II Clinical Trial of Combination Therapy with Favipiravir and Methylprednisolone for COVID-19 with Non-Critical Respiratory Failure
AU - Shindo, Yuichiro
AU - Kondoh, Yasuhiro
AU - Kada, Akiko
AU - Doi, Yohei
AU - Tomii, Keisuke
AU - Mukae, Hiroshi
AU - Murata, Naohiko
AU - Imai, Ryosuke
AU - Okamoto, Masaki
AU - Yamano, Yasuhiko
AU - Miyazaki, Yasunari
AU - Shinoda, Masahiro
AU - Aso, Hiromichi
AU - Izumi, Shinyu
AU - Ishii, Haruyuki
AU - Ito, Ryota
AU - Saito, Akiko M.
AU - Saito, Toshiki I.
AU - Hasegawa, Yoshinori
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - Adverse events
KW - Mechanical ventilation
KW - Mortality
KW - Severe acute respiratory syndrome coronavirus 2
KW - Systemic corticosteroids
UR - https://www.scopus.com/pages/publications/85112629084
UR - https://www.scopus.com/inward/citedby.url?scp=85112629084&partnerID=8YFLogxK
U2 - 10.1007/s40121-021-00512-9
DO - 10.1007/s40121-021-00512-9
M3 - Article
AN - SCOPUS:85112629084
SN - 2193-8229
VL - 10
SP - 2353
EP - 2369
JO - Infectious Diseases and Therapy
JF - Infectious Diseases and Therapy
IS - 4
ER -
