Status Approved
First Submitted Date
2020/05/05
Registered Date
2020/05/11
Last Updated Date
2020/05/07
CRIS Required
WHO ICTRP (International Clinical Trial Registry Platform) Required
1. Background
CRIS Registration Number |
KCT0005003 |
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Unique Protocol ID | GNUH-2020-04-012 |
Public/Brief Title | Clinical efficacy of Nafamostat for COVID-19 pneumonia |
Scientific Title | Treatment effect of Nafamostat mesilate in patients with COVID-19 pneumonia: open labelled randomized controlled clinical trial |
Acronym | |
MFDS Regulated Study | Yes |
IND/IDE Protocol | No |
Registered at Other Registry | No |
Healthcare Benefit Approval Status | Submitted pending |
2. Institutional Review Board / Ethics Committee
Board Approval Status | Submitted approval |
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Board Approval Number | GNUH 2020-04-012-006 |
Approval Date | 2020-05-08 |
Institutional Review Board Name | Gyeonsang National University Hospital Institute Review Board |
Institutional Review Board Address | 79, Gangnam-ro, Jinju-si, Gyeongsangnam-do |
Institutional Review Board Telephone | 055-750-9250 |
Data Monitoring Committee | No |
3. Contact Details
Contact Person for Principal Investigator / Scientific Queries | |
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Name | IN-GYU BAE |
Title | Professor |
Telephone | +82-55-750-8055 |
Affiliation | Gyeongsang National University Hospital |
Address | 79 Gangnam-ro, Jinju, South Korea |
Contact Person for Public Queries | |
Name | IN-GYU BAE |
Title | Professor |
Telephone | +82-55-750-8055 |
Affiliation | Gyeongsang National University Hospital |
Address | 79 Gangnam-ro, Jinju, South Korea |
Contact Person for Updating Information | |
Name | IN-GYU BAE |
Title | Professor |
Telephone | +82-55-750-8055 |
Affiliation | Gyeongsang National University Hospital |
Address | 79 Gangnam-ro, Jinju, South Korea |
4. Status
Study Site | Multi-center Number of center : 7 | |
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Overall Recruitment Status | Not yet recruiting | |
Date of First Enrollment | 2020-05-25 Anticipated | |
Target Number of Participant | 84 | |
Primary Completion Date | 2021-03-31 , Anticipated | |
Study Completion Date | 2021-04-21 , Anticipated | |
Recruitment Status by Participating Study Site 1 | ||
Name of Study | Pusan National University Hospital | |
Recruitment Status | Not yet recruiting | |
Date of First Enrollment | 2020-06-01 , | |
Recruitment Status by Participating Study Site 2 | ||
Name of Study | Seoul National University Bundang Hospital | |
Recruitment Status | Not yet recruiting | |
Date of First Enrollment | 2020-06-01 , | |
Recruitment Status by Participating Study Site 3 | ||
Name of Study | Seoul Medical Center | |
Recruitment Status | Not yet recruiting | |
Date of First Enrollment | 2020-06-01 , | |
Recruitment Status by Participating Study Site 4 | ||
Name of Study | Pusan National University Yangsan Hospital | |
Recruitment Status | Not yet recruiting | |
Date of First Enrollment | 2020-06-01 , | |
Recruitment Status by Participating Study Site 5 | ||
Name of Study | Chungnam National University Hospital | |
Recruitment Status | Not yet recruiting | |
Date of First Enrollment | 2020-06-01 , | |
Recruitment Status by Participating Study Site 6 | ||
Name of Study | Chungbuk National University Hospital | |
Recruitment Status | Not yet recruiting | |
Date of First Enrollment | 2020-06-01 , | |
Recruitment Status by Participating Study Site 7 | ||
Name of Study | Myongji Hospital | |
Recruitment Status | Not yet recruiting | |
Date of First Enrollment | 2020-06-01 , |
5. Source of Monetary / Material Support
1. Source of Monetary/Material Support | |
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Organization Name | Ministry of Science and ICT |
Organization Type | Government |
Project ID | 2020M3E9A1085862 |
6. Sponsor Organization
1. Sponsor Organization | |
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Organization Name | Gyeongsang National University Hospital |
Organization Type | Medical Institute |
7. Study Summary
Lay Summary | - Research purpose: Contribute to the establishment of therapeutic strategy by evaluating the therapeutic effect of Nafamostat by a randomized trial. - Research background: 1. 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. 2. 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. * Nafamostat mesilate, ‘serine protease inhibitor’, is used for prevention of perfused blood coagulation when patients with hemorrhagic lesion or tendency to hemorrhage go through extracorporeal circulation instead of heparin, for treatment of patients with Disseminated intravascular coagulation (DIC), and improvement fo symptoms of acute pancreatitis. ※ Proposed 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 |
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8. Study Design
Study Type | Interventional Study |
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Study Purpose | Treatment |
Phase | Phase2 |
Intervention Model | Parallel |
Blinding/Masking | Open |
Allocation | RCT |
Intervention Type | Drug |
Intervention Description | 1. Control group: Conventional treatment * Conventional treatment: Treatments with Lopinavir / ritonavir, Hydroxychloroquine, Oxygen therapy, Non-invasive and invasive ventilaton, antibiotic therapy, renal-replacement therapy (e.g. CRRT, HD), extracorporeal membrane oxygenation (ECMO), etc. can be applied as a standard treatment for patients eligible for this study. 2. Intervention group: Conventional treatment + Nafamostat IV * Nafamostat injection - Dosage: The researcher administers a dose of 0.1 to 0.2 mg / kg / hr (2.4 to 4.8 mg / kg / 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. |
Number of Arms | 2 |
Arm 1 |
Arm Label Control group |
Target Number of Participant 42 |
|
Arm Type No intervention |
|
Arm Description Conventional treatment : Treatments with Lopinavir / ritonavir, Hydroxychloroquine, Oxygen therapy, Non-invasive and invasive ventilaton, antibiotic therapy, renal-replacement therapy (e.g. CRRT, HD), extracorporeal membrane oxygenation (ECMO), etc. can be applied as a standard treatment for patients eligible for this study. |
|
Arm 2 |
Arm Label Intervention group |
Target Number of Participant 42 |
|
Arm Type Experimental |
|
Arm Description Conventional treatment + Nafamostat IV * Nafamostat IV injection - Dosage: The researcher administers a dose of 0.1 to 0.2 mg / kg / hr (2.4 to 4.8 mg / kg / 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. |
9. Subject Eligibility
Condition(s)/Problem(s) |
* (U00-U99)Codes for special purposes (U07.1)Coronavirus disease 2019, virus identified [COVID-19, virus identified] SARS-CoV-2 COVID-19 Pneumonia |
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Rare Disease | No |
Inclusion Criteria |
Gender Both |
Age 18Year~No Limit |
|
Description 1. 18 years old or older 2. Patients who have been confirmed of COVID-19 infection and has evidence for pneumonia A. Confirmation of COVID-19 infection by RT-PCR of SARS-CoV-2 B. Definite diagnosis of new infiltration of the lungs by chest CT scan of chest radiographic inspection 3. Patients who are within 72 hours of COVID-19 pneumonia confirmation 4. Patients with 3 (hospitalization, not requiring supplemental oxygen) or higher in seven-category ordinal scale of clinical status 5. Patients who are eligible for diagnosis/evaluation to chest CT scan and related to it 6. 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 |
1. Patients who have a record of HIV or AIDS 2. 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 3. Patients at high risk of death within 3 days of randomized assignment, by the judge of the investigator 4. Patients with liver cirrhosis whose Child-Puch score is B or C 5. Patients who have liver disease abnormalities with ALT or AST > 5 times ULN 6. 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 7. Patients who are not appropriate for the test, as the investigator’s opinion 8. Patients who have hypersensitivity to the investigational drug |
Healthy Volunteers | No |
10. Outcome Measure(s)
Type of Primary Outcome | /Safety/Efficacy | |
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Primary Outcome(s) 1 | ||
Outcome | 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 |
|
Timepoint | Day 14 and Day 28 |
|
Secondary Outcome(s) 1 | ||
Outcome | 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. |
|
Timepoint | from day 1 through 28 days |
|
Secondary Outcome(s) 2 | ||
Outcome | Clinical status assessed by 7-category ordinal scale |
|
Timepoint | days 7, 14, 28 |
|
Secondary Outcome(s) 3 | ||
Outcome | Change in National Early Warning Score (NEWS) |
|
Timepoint | from day 1 through day 28 |
|
Secondary Outcome(s) 4 | ||
Outcome | Time to National Early Warning Score (NEWS) of ≤ 2 and maintained for 24 hours |
|
Timepoint | from day 1 through day 28 |
|
Secondary Outcome(s) 5 | ||
Outcome | Duration of hospitalization |
|
Timepoint | from day 1 through day 28 |
|
Secondary Outcome(s) 6 | ||
Outcome | Duration of new non-invasive ventilation or high flow oxygen use |
|
Timepoint | from day 1 through day 28 |
|
Secondary Outcome(s) 7 | ||
Outcome | Incidence of new non-invasive ventilation or high flow oxygen use |
|
Timepoint | from day 1 through day 28 |
|
Secondary Outcome(s) 8 | ||
Outcome | Duration of new supplement oxygen use |
|
Timepoint | from day 1 through day 28 |
|
Secondary Outcome(s) 9 | ||
Outcome | Incidence of new supplement oxygen use |
|
Timepoint | from day 1 through day 28 |
|
Secondary Outcome(s) 10 | ||
Outcome | Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use |
|
Timepoint | from day 1 through day 28 |
|
Secondary Outcome(s) 11 | ||
Outcome | Incidence of new ventilator or extracorporeal membrane oxygenation (ECMO) use |
|
Timepoint | from day 1 through day 28 |
|
Secondary Outcome(s) 12 | ||
Outcome | Mortality at day 28 |
|
Timepoint | from day 1 through day 28 |
|
Secondary Outcome(s) 13 | ||
Outcome | Time (days) from treatment initiation to death |
|
Timepoint | from day 1 through day 28 |
|
Secondary Outcome(s) 14 | ||
Outcome | Viral load change (log10 viral load) of nasopharyngeal swab and sputum sample for SARS-CoV-2 quantitative RT-PCR |
|
Timepoint | day 0, 3, 7, 10, 14, and 21 |
|
Secondary Outcome(s) 15 | ||
Outcome | Adverse events that occurred during treatment |
|
Timepoint | from day 1 through day 28 |
11. Study Results and Publication
Result Registered | No |
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12. Sharing of Study Data(Deidentified Individual-Patient Data, IPD)
Sharing Statement | Yes |
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Time of Sharing | 2021. 7 |
Way of Sharing | Available on Request
(ttezebae@gmail.com) |
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