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Clinical Efficacy of Nafamostat Mesylate for COVID-19 Pneumonia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04418128
Recruitment Status : Not yet recruiting
First Posted : June 5, 2020
Last Update Posted : June 9, 2020
Sponsor:
Information provided by (Responsible Party):
IN-GYU BAE, MD, Gyeongsang National University Hospital

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.


Condition or disease Intervention/treatment Phase
Corona Virus Infection COVID-19 Drug: Nafamostat Mesylate Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment
Official Title: Treatment Effect of Nafamostat Mesylate in Patients With COVID-19 Pneumonia: Open Labelled Randomized Controlled Clinical Trial
Estimated Study Start Date : June 10, 2020
Estimated Primary Completion Date : March 30, 2021
Estimated Study Completion Date : April 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pneumonia

Arm Intervention/treatment
No Intervention: Conventional therapy
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).
Experimental: Conventional therapy + Nafamostat mesylate
  • 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.
Drug: Nafamostat Mesylate
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 Measures :
  1. Proportion of patients with clinical improvement [ Time Frame: Day 14 & Day 28 ]

    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.


Secondary Outcome Measures :
  1. Time to clinical improvement (TTCI) [ Time Frame: up to 28 days ]
    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.

  2. Clinical status assessed by 7-category ordinal scale [ Time Frame: days 7, 14, and 28 ]

    * 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.

  3. Change in National Early Warning Score (NEWS) [ Time Frame: Day 1 trough Day 28 ]
    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.

  4. Time to National Early Warning Score (NEWS) of ≤ 2 and maintained for 24 hours [ Time Frame: Day 1 through Day 28 ]
  5. Duration of hospitalization [ Time Frame: Day 1 through Day 28 ]
  6. Duration of new non-invasive ventilation or high flow oxygen use [ Time Frame: Day 1 through Day 28 ]
  7. Incidence of new non-invasive ventilation or high flow oxygen use [ Time Frame: Day 1 through Day 28 ]
  8. Duration of new supplement oxygen use [ Time Frame: Day 1 through Day 28 ]
  9. Incidence of new supplement oxygen use [ Time Frame: Day 1 through Day 28 ]
  10. Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use [ Time Frame: Day 1 through Day 28 ]
  11. Incidence of new ventilator or extracorporeal membrane oxygenation (ECMO) use [ Time Frame: Day 1 through Day 28 ]
  12. Mortality at day 28 [ Time Frame: Day 1 through Day 28 ]
  13. Time (days) from treatment initiation to death [ Time Frame: Day 1 through Day 28 ]
  14. 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 ]
  15. 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 ]
  16. Adverse events that occurred during treatment [ Time Frame: Day 1 through Day 28 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • Inclusion Criteria:

    1. 18 years old or older
    2. 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
    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

      • 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.
    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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04418128


Contacts
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Contact: IN-GYU BAE, MD +82-55-750-8055 ttezebae@gmail.com
Contact: Kyunglan Moon, MD lannya@naver.com

Sponsors and Collaborators
Gyeongsang National University Hospital
Investigators
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Principal Investigator: IN-GYU BAE, MD Gyeongsang National University Hospital
Publications of Results:
Other Publications:
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Responsible Party: IN-GYU BAE, MD, Professor, Gyeongsang National University Hospital
ClinicalTrials.gov Identifier: NCT04418128    
Other Study ID Numbers: 2020-04-012
First Posted: June 5, 2020    Key Record Dates
Last Update Posted: June 9, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by IN-GYU BAE, MD, Gyeongsang National University Hospital:
Nafamostat
Pneumonia
TMPSS2
Serine protease inhibitor
Additional relevant MeSH terms:
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Coronavirus Infections
Severe Acute Respiratory Syndrome
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Virus Diseases
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Nafamostat
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Anticoagulants
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Trypsin Inhibitors
Serine Proteinase Inhibitors
Complement Inactivating Agents
Immunosuppressive Agents
Immunologic Factors