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Multicenter, Single blinded Randomized Controlled, Comparative Study to Evaluate the Efficacy and Safety of Favipiravir and Nafamostat Mesilate in Patients with COVID-19 Pneumonia

Combination therapy of Favipiravir and Nafamostat Mesilate in Patients with COVID-19 Pneumonia

45

A total of 45 patients were enrolled. [Nafamostat with favipiravir group (group A): 21 cases] Gender: 12 males (57%), 9 females (43%), Median age at informed consent: 50.0, Median BMI (kg/m2): 22.84, Complications: diabetes mellitus 4 cases (19.0%), cardiovascular disease 0 cases (0%), chronic pulmonary disease 1 case (4.8%), other complications in 13 cases (31.9%), drug allergy 0 case (0%), other allergies in 2 cases (9.5%) [Favipiravir group (group B): 24 cases] Gender: 15 males (63%), 9 females (37%), Median age at informed consent: 54.0, Median BMI (kg/m2): 23.65, Complications: diabetes mellitus 5 cases (20.8%), cardiovascular disease 0 cases (0%), chronic pulmonary disease 1 case (4.2%), other complications in 14 cases (58.3%), drug allergy 0 case (0%), other allergies in 3 cases (12.5%)

Enrollment began on May 1, 2020 and ended on Dec. 15, 2021. The first patient was enrolled on Jun. 11, 2020. The primary outcome and number of target cases were changed on Oct. 2020 and on Dec. 2021, respectively. Database was locked on Feb. 2022 and statistical analysis was completed on Mar. 2022. In this study, 45 patients were enrolled and administrated with the study drugs. Although 11 patients discontinued during the study period, 45 patients were included in the analysis.

All adverse event was 19/21 (90.5%) in group A and 20/24 (83.3%) in group B. In group A, adverse events which cannot be ruled out with the study drug occurred in 16 (76.2%) and in 18 (85.7%). In group B, adverse events which cannot be ruled out with the study drug occurred in 18 (75.0%). No difference was observed between two group (p=0.800). No serious adverse events or deaths were reported.

[Primary outcome] There was no significant difference in changes in the Clinical Progression Scale between groups (median, -0.444 vs. -0.150; least-squares mean difference, -0.294; p=0.364). [Secondary outcomes] The time to improvement in body temperature was significantly shorter in the combination group (5.0 days; 95% CI, 4.0-7.0) than in the favipiravir group (9.0 days; 95% CI, 7.0-18.0; p=0.009). Changes in SpO2 on day 7 were greater in the combination group than in the favipiravir group (0.526% vs. -1.304%; least-squares mean difference, 1.831; p=0.022). However, the rate of change in viral load on day 3 and 5 did not differ between two groups.

Nafamostat combined with favipiravir did not improve clinical progression. However, early defervescence and recovery of SpO2 were observed in the combination group.

Mar. 31, 2023

No

None

https://jrct.niph.go.jp/latest-detail/jRCTs031200026

Shu Okugawa

The University of Tokyo Hospital

7-3-1, Hongo, Bunkyo-ku, Tokyo

okugawa-tky@g.ecc.u-tokyo.ac.jp

Shu Okugawa

The University of Tokyo Hospital

7-3-1, Hongo, Bunkyo-ku, Tokyo

+81-3-3815-5411

okugawa-tky@g.ecc.u-tokyo.ac.jp

Complete

May. 01, 2020

Interventional

randomized controlled trial

single blind

active control

parallel assignment

treatment purpose

1) Patients who have given written consent to participate in the study
2) SARS-CoV-2 test positive
3) Patients with pneumonia on chest image
4) Patients with fever over 37.5 degrees
5) Pregnancy test-negative

1) Patients with fever over 37.5 degrees for more than 10 days
2) Patients having less than 93% of oxygen saturation (SpO2) in without the oxygen administration
3) Patients having cardiac dysfunctions such as congestive heart failure, having severe liver dysfunction, and having renal dysfunction requiring dialysis
4) Patients having history of gout or currently undergoing treatment of gout or hyperuricemia
5) Patients having disorders of consciousness such as disorientation
6) Patients who are pregnant or who may be pregnant
7)Patients who are suspected to have an infection with a microorganism other than SARS-COV-2, causative organism of pneumonia.
8) Patients with hyperkalemia or hyponatremia
9) Patients who are considered inappropriate for inclusion in the study by the investigator

Both

Coronavirus Disease 2019 (COVID-19)

COVID-19 patients are randomly assigned to the group which adds Favipiravir and Nafamostat Mesilate to standard treatment or the group which add Favipiravir to standard treatment

COVID-19

Change in patient condition on a 10-point scale from baseline to day7

1) Change in patient condition on a 10-point scale from baseline to day4 and day8
2) Change in SARS-CoV-2 viral load
3) Duration of fever and respiratory symptom
4) Change of clinical manifestations
5) Change of vital signs
6) Change of NEWS (National Early Warning Score)
7) Remission rate of chest image findings
8) Ratio of patients who required oxygen administration and mean duration of oxygen administration
9) Ratio of patients who required mechanical ventilation and mean duration of mechanical ventilation
10) Change of WBC count, hemoglobin, platelet count, creatinine, blood glucose, total bilirubin, ALT, PT, APTT,and D-dimer

+81-3-5841-0818

April. 30, 2020

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