Efficacy of Nafamostat in Covid-19 Patients (RACONA Study)

NCT ID: NCT04352400

Last Updated: 2023-11-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 256 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-04
• Study Completion Date: 2024-12-31

Brief Summary

RACONA is a prospective trial that will test the hypothesis that nafamostat can lower lung function deterioration and need for intensive care admission in COVID-19 patients.

Design: Adult hospitalized COVID-19 patients will be randomized in a prospective double-blind randomized placebo-controlled study to test the clinical efficacy of nafamostat mesylate (administered intravenously) on top of best standard of care.

Primary outcome measures: the time-to-clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven category ordinal scale or live discharge from the hospital, whichever comes first.

Detailed Description

Purpose: SARS-Cov-2 enters the lung cells by binding to ACE-2 and activating the protease TMPRSS2, which, therefore, can be a target for antiviral treatment. Accordingly, TMPRSS2 inhibitors prevent SARS-CoV cell entry in vitro. The most potent such inhibitors, nafamostat is being used as anticoagulant and anti-pancreatitis agent, and is approved for the treatment of cystic fibrosis as its mucolytic action can prevent lung function deterioration by owering airways infections.

RACONA study will test the hypothesize that nafamostat is useful in COVID-19 lung involvement because COVID-19 entails activation of the coagulation cascade, pulmonary embolism, and bacterial superinfections.

Conditions

COVID19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Nafamostat

Nafamostat mesylate on top of best standard of care.

Group Type: ACTIVE_COMPARATOR

Nafamostat Mesilate

Intervention Type: DRUG

administered intravenously as a continuous infusion

Placebo

Placebo on top of best standard of care.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

administered intravenously as a continuous infusion

Interventions

Nafamostat Mesilate

administered intravenously as a continuous infusion

Intervention Type: DRUG

Placebo

administered intravenously as a continuous infusion

Intervention Type: DRUG

Other Intervention Names

no alternative name. Commercial brands are available.; no alternative name.

Eligibility Criteria

Inclusion Criteria

• Hospitalized, COVID-19 positive, between 18 and ≤ 85 years of age;
• Signed Inform Consent Form;
• Body temperature > 37.3 ℃;
• Oxygenation criterion (any of the following): i) Oxygen saturation ≤94% on Room Air; ii) PaO2/FiO2 ratio ≤300 mmHg but > 100 mmHg, if patient on supplemental oxygen; iii) SpO2/FiO2<200 if no arterial blood gas available;
• Respiratory rate (RR) ≥ 25 beats/min.

Exclusion Criteria

• Pregnant or lactating females;
• Unwillingness or inability to complete the study.
• Rapidly deteriorating clinical condition or low likelihood to complete the study according to the investigator;
• eGFR < 30 ml/min/m2 assessed with CKD EPI formula;
• Current or chronic history of liver disease (Child Pugh score ≥ 10), or known hepatic or biliary abnormalities;
• Participation in a clinical trial with an investigational product within the following time period prior to the first dosing day in the current study: 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer);
• Patients requiring high doses of loop diuretics (i.e. > 240 mg furosemide daily) with significant intravascular volume depletion, as assessed clinically;
• History of allergy;
• History of sensitivity to heparin or heparin-induced thrombocytopenia;
• Unstable hemodynamics in the preceding 4 hours (SBP < 90 mmHg, and/or vasoactive agents required);
• Hemoglobin < 7 at time of drug infusion. Transfusion is allowed to increase hemoglobin levels before entry into the study;
• Malignancy or any other condition for which estimated 6-month mortality >50%;
• Arterial blood pH less than 7.2;
• Known evidence of chronic interstitial infiltration at imaging;
• Known hospitalization within the past six months for respiratory failure (PaCO2 > 50 mmHg or PaO2 < 55 mmHg, or oxygen saturation <88% on FiO2 = 0.21);
• Known chronic vascular disease resulting in severe exercise restriction (i.e. unable to perform household duties);
• Known secondary polycythemia, severe pulmonary hypertension, or ventilator dependency;
• Known vasculitis with diffuse alveolar hemorrhage;.
• Pre-existing renal failure on hemodialysis or peritoneal dialysis requiring renal replacement therapy;
• Extracorporeal membrane oxygenation (ECMO);
• Immunosuppressive treatment;
• Patient in trials for COVID-19 within 30 days before;
• Unstable hemodynamics in the preceding 4 hours (MAP ≤ 65 mmHg, or SAP < 90 mmHg, DAP < 60 mmHg, and vasoactive agents required);
• Hyperkalemia , i.e. serum K+ levels > 5.0 mEq/L;
• Severe active bleeding;
• Any other uncontrolled comorbidities that increase the risks associated with the study drug administration, as assessed by the medical expert team.

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

Sponsors

Yokohama City University

OTHER

Sponsor Role: collaborator

University of Zurich

OTHER

Sponsor Role: collaborator

University Hospital Padova

OTHER

Sponsor Role: lead

Responsible Party

Gian Paolo Rossi, MD, FAHA, FACC

Prof.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gian Paolo Rossi, Prof.

Role: PRINCIPAL_INVESTIGATOR

University of Padova, Italy

Locations

Azienda Ospedale Università di Padova

Padua, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Gian Paolo Rossi, Prof.

Role: CONTACT

gianpaolo.rossi@unipd.it

0039049821 ext. 2279

Facility Contacts

Gian Paolo Rossi, Prof.

Role: primary

References

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Reference Type: RESULT

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Reference Type: RESULT

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Minakata D, Fujiwara SI, Ikeda T, Kawaguchi SI, Toda Y, Ito S, Ochi SI, Nagayama T, Mashima K, Umino K, Nakano H, Yamasaki R, Morita K, Kawasaki Y, Sugimoto M, Yamamoto C, Ashizawa M, Hatano K, Sato K, Oh I, Ohmine K, Muroi K, Ohmori T, Kanda Y. Comparison of gabexate mesilate and nafamostat mesilate for disseminated intravascular coagulation associated with hematological malignancies. Int J Hematol. 2019 Feb;109(2):141-146. doi: 10.1007/s12185-018-02567-w. Epub 2018 Dec 8.

Reference Type: RESULT

PMID: 30536180 (View on PubMed)

Yu G, Li S, Wan R, Wang X, Hu G. Nafamostat mesilate for prevention of post-ERCP pancreatitis: a meta-analysis of prospective, randomized, controlled trials. Pancreas. 2015 May;44(4):561-9. doi: 10.1097/MPA.0000000000000310.

Reference Type: RESULT

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Ferreira FL, Bota DP, Bross A, Melot C, Vincent JL. Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA. 2001 Oct 10;286(14):1754-8. doi: 10.1001/jama.286.14.1754.

Reference Type: RESULT

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Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.

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Study Documents

Document Type: Individual Participant Data Set

The link https://ncov.medsci.ox.ac.uk allows connection to EDCap database, a secure web platform for building and managing online databases and surveys. Data collection will use the WHO Case Record Form.

View Document

Other Identifiers

RACONA Nafamostat

Identifier Type: -

Identifier Source: org_study_id