In-vitro studies revealed that nafamostat mesylate has antiviral activity against Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and anti-inflammatory and anti-coagulation effect. However, there is no clinical studies on the efficacy of nafamostat in patients with COVID-19. This study is conducted to evaluate the clinical efficacy of nafamostate mesylate in adult patients hospitalized with COVID-19 pneumonia.
* The COVID-19 epidemic expanded to the whole world since it started from the Wuhan area in China in Dec. 2019. The Republic of Korea experiences a sharp increase in the patient since 24th Feb. 2020. An analysis of more than 70,000 patients in China, about 15% of them cause severe pneumonia, 5% require treatment in the intensive care unit, half of them die of the disease. * There is no proven therapeutics for COVID-19 patients yet. Currently, the treatment with Kaletra, Hydroxychloroquine, etc. did not show apparent effect, and there are no other drugs that can apply to patients who get worse even with those drugs or severe. * There are research reports that defective innate immunity and accelerated activation of the complement cascade, caused by the SARS-CoV-2, induce rapidly progressing pneumonitis. * Action mechanism of Nafamostat mesilate A. Show anti-viral effect by an inhibition serine protease, which is required for the host membrane fusion of viral envelop protein. In vitro experiments showed that the drug is effective in MERS-CoV, Influenza virus, and SARS-CoV-2. B. Show anti-inflammatory effect by inhibition of the complement pathway, and inhibition of cytokine production. This study is conducted to evaluate the clinical efficacy of nafamostate mesylate in adult patients hospitalized with COVID-19 pneumonia.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
84
The Nafamostat mesilate group received continuous intravenous infusion of 0.1-0.2 mg/kg/h of nafamostat mesilate mixed with 5% DW.
Proportion of patients with clinical improvement
Proportion of patients with clinical improvement as defined by live discharge from hospital or a decline of 2 categories on the seven-category ordinal scale of clinical status. \* Seven-category ordinal scale of clinical status 1. not hospitalized with resumption of normal activities; 2. not hospitalized, but unable to resume normal activities; 3. hospitalization, not requiring supplemental oxygen; 4. hospitalization, requiring supplemental oxygen; 5. hospitalization, requiring nasal high-flow oxygen therapy and/or noninvasive mechanical ventilation; 6. hospitalization, requiring extracorporeal membrane oxygenation and/or invasive mechanical ventilation; 7. death.
Time frame: Day 14 & Day 28
Time to clinical improvement (TTCI)
Time to clinical improvement (TTCI) was defined as time from randomization to a decline of 2 categories on the seven-category ordinal scale of clinical status or live discharge from the hospital, whichever came first.
Time frame: up to 28 days
Clinical status assessed by 7-category ordinal scale
\* Seven-category ordinal scale of clinical status 1. not hospitalized with resumption of normal activities; 2. not hospitalized, but unable to resume normal activities; 3. hospitalization, not requiring supplemental oxygen; 4. hospitalization, requiring supplemental oxygen; 5. hospitalization, requiring nasal high-flow oxygen therapy and/or noninvasive mechanical ventilation; 6. hospitalization, requiring extracorporeal membrane oxygenation and/or invasive mechanical ventilation; 7. death. * Higher scores of Seven-category ordinal scale mean serious clinical status.
Time frame: days 7, 14, and 28
Change in National Early Warning Score (NEWS)
The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The range of NEW score is from zero to 23. Higher scores of NEWS mean the higher risk of poor outcomes. The NEW Score is being used as an efficacy measure.
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Time frame: Day 1 trough Day 28
Time to National Early Warning Score (NEWS) of ≤ 2 and maintained for 24 hours
Time frame: Day 1 through Day 28
Duration of hospitalization
Time frame: Day 1 through Day 28
Duration of new non-invasive ventilation or high flow oxygen use
Time frame: Day 1 through Day 28
Incidence of new non-invasive ventilation or high flow oxygen use
Time frame: Day 1 through Day 28
Duration of new supplement oxygen use
Time frame: Day 1 through Day 28
Incidence of new supplement oxygen use
Time frame: Day 1 through Day 28
Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use
Time frame: Day 1 through Day 28
Incidence of new ventilator or extracorporeal membrane oxygenation (ECMO) use
Time frame: Day 1 through Day 28
Mortality at day 28
Time frame: Day 1 through Day 28
Time (days) from treatment initiation to death
Time frame: Day 1 through Day 28
Proportions of patients with a negative nasopharyngeal swab and sputum sample for SARS-CoV-2 quantitative RT-PCR
Time frame: days 3, 7, 10, 14, and 21
Viral load change (log10 viral load) of nasopharyngeal swab and sputum sample for SARS-CoV-2 quantitative RT-PCR
Time frame: days 3, 7, 10, 14, and 21
Adverse events that occurred during treatment
Time frame: Day 1 through Day 28