Back to resultsClinical Efficacy of Nafamostat Mesylate for COVID-19 Pneumonia
Primary Purpose
Corona Virus Infection, COVID-19
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Nafamostat Mesylate
Sponsored by
About this trial
This is an interventional treatment trial for Corona Virus Infection focused on measuring Nafamostat, Pneumonia, TMPSS2, Serine protease inhibitor
Eligibility Criteria
Inclusion Criteria:
- 18 years old or older
Patients who have been confirmed of COVID-19 infection and has evidence for pneumonia
- Confirmation of COVID-19 infection by RT-PCR of SARS-CoV-2
- Definite diagnosis of new infiltration of the lungs by chest CT scan of chest radiographic inspection
- Patients who are within 72 hours of COVID-19 pneumonia confirmation
Patients with 3(hospitalization, not requiring supplemental oxygen) or higher in seven-category ordinal scale of clinical status
Seven-category ordinal scale of clinical status
- not hospitalized with resumption of normal activities;
- not hospitalized, but unable to resume normal activities;
- hospitalization, not requiring supplemental oxygen;
- hospitalization, requiring supplemental oxygen;
- hospitalization, requiring nasal high-flow oxygen therapy and/or noninvasive mechanical ventilation;
- hospitalization, requiring extracorporeal membrane oxygenation and/or invasive mechanical ventilation;
- death.
- Patients who are eligible for diagnosis/evaluation to chest CT scan and related to it
- Patients should be able to understand the essence of the clinical trial and to submit a written consent document. For the patients who can understand the nature of the research but cannot sign the document, a relative can agree to the study.
Exclusion Criteria:
- Patients who have a record of HIV or AIDS
- Female patients, either who are pregnant within 6 months before the investigation, who breast-fed babies within 3 months before the investigation, or who may get pregnant or breast-feed within 1 month after the investigation is over
- Patients at high risk of death within 3 days of randomized assignment, by the judge of the investigator
- Patients with liver cirrhosis whose Child-Puch score is B or C
- Patients who have liver disease abnormalities with ALT or AST > 5 times ULN
- Patients who can be in danger or who shows clinically-important other conditions which may interfere with the evaluation or completion of the test procedure, as the investigator's opinion
- Patients who are not appropriate for the test, as the investigator's opinion
- Patients who have hypersensitivity to the investigational drug
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Conventional therapy
Conventional therapy + Nafamostat mesylate
Arm Description
The conventional therapy comprised, as necessary, Lopinavir/ritonavir, Hydroxychlorquine, supplemental oxygen, Non-invasive and invasive ventilation, antibiotic agents, renal-replacement therapy (e.g.: CRRT, HD), extracorporeal membrane oxygenation (ECMO).
The conventional therapy comprised, as necessary, Lopinavir/ritonavir, Hydroxychlorquine, supplemental oxygen, Non-invasive and invasive ventilation, antibiotic agents, renal-replacement therapy (e.g.: CRRT, HD), extracorporeal membrane oxygenation (ECMO). Nafamostat mesylate injection day), taking into account the severity and underlying disease of the clinical trial patient. Method of administration: Nafamostat injection is mixed with 1,000 ml of 5% DW infusion, followed by continuous infusion over 24 hours. Duration of administration: The researcher administers for 10-14 days considering the severity and underlying disease of the clinical trial patient.
Outcomes
Primary Outcome Measures
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
not hospitalized with resumption of normal activities;
not hospitalized, but unable to resume normal activities;
hospitalization, not requiring supplemental oxygen;
hospitalization, requiring supplemental oxygen;
hospitalization, requiring nasal high-flow oxygen therapy and/or noninvasive mechanical ventilation;
hospitalization, requiring extracorporeal membrane oxygenation and/or invasive mechanical ventilation;
death.
Secondary Outcome Measures
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.
Clinical status assessed by 7-category ordinal scale
* Seven-category ordinal scale of clinical status
not hospitalized with resumption of normal activities;
not hospitalized, but unable to resume normal activities;
hospitalization, not requiring supplemental oxygen;
hospitalization, requiring supplemental oxygen;
hospitalization, requiring nasal high-flow oxygen therapy and/or noninvasive mechanical ventilation;
hospitalization, requiring extracorporeal membrane oxygenation and/or invasive mechanical ventilation;
death.
Higher scores of Seven-category ordinal scale mean serious clinical status.
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.
Time to National Early Warning Score (NEWS) of ≤ 2 and maintained for 24 hours
Duration of hospitalization
Duration of new non-invasive ventilation or high flow oxygen use
Incidence of new non-invasive ventilation or high flow oxygen use
Duration of new supplement oxygen use
Incidence of new supplement oxygen use
Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use
Incidence of new ventilator or extracorporeal membrane oxygenation (ECMO) use
Mortality at day 28
Time (days) from treatment initiation to death
Proportions of patients with a negative nasopharyngeal swab and sputum sample for SARS-CoV-2 quantitative RT-PCR
Viral load change (log10 viral load) of nasopharyngeal swab and sputum sample for SARS-CoV-2 quantitative RT-PCR
Adverse events that occurred during treatment
Full Information
NCT ID
NCT04418128
First Posted
June 3, 2020
Last Updated
June 6, 2020
Sponsor
Gyeongsang National University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04418128
Brief Title
Clinical Efficacy of Nafamostat Mesylate for COVID-19 Pneumonia
Official Title
Treatment Effect of Nafamostat Mesylate in Patients With COVID-19 Pneumonia: Open Labelled Randomized Controlled Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Unknown status
Study Start Date
June 10, 2020 (Anticipated)
Primary Completion Date
March 30, 2021 (Anticipated)
Study Completion Date
April 30, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Gyeongsang National University Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Corona Virus Infection, COVID-19
Keywords
Nafamostat, Pneumonia, TMPSS2, Serine protease inhibitor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
This study is an open-labelled, randomized clinical trial to evaluate the efficacy of nafamostate in patients with COVID-19 pneumonia.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
84 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Conventional therapy
Arm Type
No Intervention
Arm Description
The conventional therapy comprised, as necessary, Lopinavir/ritonavir, Hydroxychlorquine, supplemental oxygen, Non-invasive and invasive ventilation, antibiotic agents, renal-replacement therapy (e.g.: CRRT, HD), extracorporeal membrane oxygenation (ECMO).
Arm Title
Conventional therapy + Nafamostat mesylate
Arm Type
Experimental
Arm Description
The conventional therapy comprised, as necessary, Lopinavir/ritonavir, Hydroxychlorquine, supplemental oxygen, Non-invasive and invasive ventilation, antibiotic agents, renal-replacement therapy (e.g.: CRRT, HD), extracorporeal membrane oxygenation (ECMO).
Nafamostat mesylate injection day), taking into account the severity and underlying disease of the clinical trial patient.
Method of administration: Nafamostat injection is mixed with 1,000 ml of 5% DW infusion, followed by continuous infusion over 24 hours.
Duration of administration: The researcher administers for 10-14 days considering the severity and underlying disease of the clinical trial patient.
Intervention Type
Drug
Intervention Name(s)
Nafamostat Mesylate
Intervention Description
The Nafamostat mesilate group received continuous intravenous infusion of 0.1-0.2 mg/kg/h of nafamostat mesilate mixed with 5% DW.
Primary Outcome Measure Information:
Title
Proportion of patients with clinical improvement
Description
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
not hospitalized with resumption of normal activities;
not hospitalized, but unable to resume normal activities;
hospitalization, not requiring supplemental oxygen;
hospitalization, requiring supplemental oxygen;
hospitalization, requiring nasal high-flow oxygen therapy and/or noninvasive mechanical ventilation;
hospitalization, requiring extracorporeal membrane oxygenation and/or invasive mechanical ventilation;
death.
Time Frame
Day 14 & Day 28
Secondary Outcome Measure Information:
Title
Time to clinical improvement (TTCI)
Description
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
Title
Clinical status assessed by 7-category ordinal scale
Description
* Seven-category ordinal scale of clinical status
not hospitalized with resumption of normal activities;
not hospitalized, but unable to resume normal activities;
hospitalization, not requiring supplemental oxygen;
hospitalization, requiring supplemental oxygen;
hospitalization, requiring nasal high-flow oxygen therapy and/or noninvasive mechanical ventilation;
hospitalization, requiring extracorporeal membrane oxygenation and/or invasive mechanical ventilation;
death.
Higher scores of Seven-category ordinal scale mean serious clinical status.
Time Frame
days 7, 14, and 28
Title
Change in National Early Warning Score (NEWS)
Description
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.
Time Frame
Day 1 trough Day 28
Title
Time to National Early Warning Score (NEWS) of ≤ 2 and maintained for 24 hours
Time Frame
Day 1 through Day 28
Title
Duration of hospitalization
Time Frame
Day 1 through Day 28
Title
Duration of new non-invasive ventilation or high flow oxygen use
Time Frame
Day 1 through Day 28
Title
Incidence of new non-invasive ventilation or high flow oxygen use
Time Frame
Day 1 through Day 28
Title
Duration of new supplement oxygen use
Time Frame
Day 1 through Day 28
Title
Incidence of new supplement oxygen use
Time Frame
Day 1 through Day 28
Title
Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use
Time Frame
Day 1 through Day 28
Title
Incidence of new ventilator or extracorporeal membrane oxygenation (ECMO) use
Time Frame
Day 1 through Day 28
Title
Mortality at day 28
Time Frame
Day 1 through Day 28
Title
Time (days) from treatment initiation to death
Time Frame
Day 1 through Day 28
Title
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
Title
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
Title
Adverse events that occurred during treatment
Time Frame
Day 1 through Day 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
18 years old or older
Patients who have been confirmed of COVID-19 infection and has evidence for pneumonia
Confirmation of COVID-19 infection by RT-PCR of SARS-CoV-2
Definite diagnosis of new infiltration of the lungs by chest CT scan of chest radiographic inspection
Patients who are within 72 hours of COVID-19 pneumonia confirmation
Patients with 3(hospitalization, not requiring supplemental oxygen) or higher in seven-category ordinal scale of clinical status
Seven-category ordinal scale of clinical status
not hospitalized with resumption of normal activities;
not hospitalized, but unable to resume normal activities;
hospitalization, not requiring supplemental oxygen;
hospitalization, requiring supplemental oxygen;
hospitalization, requiring nasal high-flow oxygen therapy and/or noninvasive mechanical ventilation;
hospitalization, requiring extracorporeal membrane oxygenation and/or invasive mechanical ventilation;
death.
Patients who are eligible for diagnosis/evaluation to chest CT scan and related to it
Patients should be able to understand the essence of the clinical trial and to submit a written consent document. For the patients who can understand the nature of the research but cannot sign the document, a relative can agree to the study.
Exclusion Criteria:
Patients who have a record of HIV or AIDS
Female patients, either who are pregnant within 6 months before the investigation, who breast-fed babies within 3 months before the investigation, or who may get pregnant or breast-feed within 1 month after the investigation is over
Patients at high risk of death within 3 days of randomized assignment, by the judge of the investigator
Patients with liver cirrhosis whose Child-Puch score is B or C
Patients who have liver disease abnormalities with ALT or AST > 5 times ULN
Patients who can be in danger or who shows clinically-important other conditions which may interfere with the evaluation or completion of the test procedure, as the investigator's opinion
Patients who are not appropriate for the test, as the investigator's opinion
Patients who have hypersensitivity to the investigational drug
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
IN-GYU BAE, MD
Phone
+82-55-750-8055
Email
ttezebae@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Kyunglan Moon, MD
Email
lannya@naver.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
IN-GYU BAE, MD
Organizational Affiliation
Gyeongsang National University Hospital
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
30301856
Citation
Gralinski LE, Sheahan TP, Morrison TE, Menachery VD, Jensen K, Leist SR, Whitmore A, Heise MT, Baric RS. Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis. mBio. 2018 Oct 9;9(5):e01753-18. doi: 10.1128/mBio.01753-18.
Results Reference
background
PubMed Identifier
26166259
Citation
Yamaya M, Shimotai Y, Hatachi Y, Lusamba Kalonji N, Tando Y, Kitajima Y, Matsuo K, Kubo H, Nagatomi R, Hongo S, Homma M, Nishimura H. The serine protease inhibitor camostat inhibits influenza virus replication and cytokine production in primary cultures of human tracheal epithelial cells. Pulm Pharmacol Ther. 2015 Aug;33:66-74. doi: 10.1016/j.pupt.2015.07.001. Epub 2015 Jul 10.
Results Reference
background
PubMed Identifier
32142651
Citation
Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Muller MA, Drosten C, Pohlmann S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020 Apr 16;181(2):271-280.e8. doi: 10.1016/j.cell.2020.02.052. Epub 2020 Mar 5.
Results Reference
result
PubMed Identifier
32312781
Citation
Hoffmann M, Schroeder S, Kleine-Weber H, Muller MA, Drosten C, Pohlmann S. Nafamostat Mesylate Blocks Activation of SARS-CoV-2: New Treatment Option for COVID-19. Antimicrob Agents Chemother. 2020 May 21;64(6):e00754-20. doi: 10.1128/AAC.00754-20. Print 2020 May 21. No abstract available.
Results Reference
result
PubMed Identifier
34814935
Citation
Moon K, Hong KW, Bae IG. Treatment effect of nafamostat mesylate in patients with COVID-19 pneumonia: study protocol for a randomized controlled trial. Trials. 2021 Nov 23;22(1):832. doi: 10.1186/s13063-021-05760-1.
Results Reference
derived
Learn more about this trial
Clinical Efficacy of Nafamostat Mesylate for COVID-19 Pneumonia
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