Clinical Efficacy of Nafamostat Mesylate for COVID-19 Pneumonia

NCT ID: NCT04418128

Last Updated: 2020-06-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-10
• Study Completion Date: 2021-04-30

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.

Conditions

Corona Virus Infection; COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: NO_INTERVENTION

No interventions assigned to this group

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.

Group Type: EXPERIMENTAL

Nafamostat Mesylate

Intervention Type: DRUG

The Nafamostat mesilate group received continuous intravenous infusion of 0.1-0.2 mg/kg/h of nafamostat mesilate mixed with 5% DW.

Interventions

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.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gyeongsang National University Hospital

OTHER

Sponsor Role: lead

Responsible Party

IN-GYU BAE, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

IN-GYU BAE, MD

Role: PRINCIPAL_INVESTIGATOR

Gyeongsang National University Hospital

Central Contacts

IN-GYU BAE, MD

Role: CONTACT

ttezebae@gmail.com

+82-55-750-8055

Kyunglan Moon, MD

Role: CONTACT

lannya@naver.com

References

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.

Reference Type: BACKGROUND

PMID: 30301856 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26166259 (View on PubMed)

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.

Reference Type: RESULT

PMID: 32142651 (View on PubMed)

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.

Reference Type: RESULT

PMID: 32312781 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34814935 (View on PubMed)

Other Identifiers

2020-04-012

Identifier Type: -

Identifier Source: org_study_id