Clinical Efficacy of Nafamostat Mesylate for COVID-19 Pneumonia

NCT04418128 | Unknown Phase 2

• 1 other identifier: 2020-04-012
• Study Type: interventional
• Target: 84
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Corona Virus Infection; COVID-19

Keywords

Nafamostat; Pneumonia; TMPSS2; Serine protease inhibitor

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 14 & Day 28

Secondary Outcomes (16)

• Time to clinical improvement (TTCI)

  up to 28 days

• Clinical status assessed by 7-category ordinal scale

  days 7, 14, and 28

• Change in National Early Warning Score (NEWS)

  Day 1 trough Day 28

• Time to National Early Warning Score (NEWS) of ≤ 2 and maintained for 24 hours

  Day 1 through Day 28

• Duration of hospitalization

  Day 1 through Day 28

Study Arms (2)

Conventional therapy

NO INTERVENTION

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).

Conventional therapy + Nafamostat mesylate

EXPERIMENTAL

* 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

Interventions

Nafamostat Mesylate DRUG

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

Conventional therapy + Nafamostat mesylate

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gyeongsang National University Hospital: lead

Related Publications (5)

• 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.

  PMID: 30301856 BACKGROUND

• 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.

  PMID: 26166259 BACKGROUND

• 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.

  PMID: 32142651 RESULT

• 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.

  PMID: 32312781 RESULT

• 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.

  PMID: 34814935 DERIVED

MeSH Terms

Conditions

Coronavirus Infections; COVID-19; Pneumonia

Interventions

nafamostat

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Pneumonia, Viral; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• IN-GYU BAE, MD

  Gyeongsang National University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

IN-GYU BAE, MD

CONTACT

+82-55-750-8055; ttezebae@gmail.com

Kyunglan Moon, MD

CONTACT

lannya@naver.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This study is an open-labelled, randomized clinical trial to evaluate the efficacy of nafamostate in patients with COVID-19 pneumonia.

Study Record Dates

• First Submitted: June 3, 2020
• First Posted: June 5, 2020
• Study Start: June 10, 2020
• Primary Completion: March 30, 2021
• Study Completion: April 30, 2021
• Last Updated: June 9, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share