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

October 31, 2023 updated by: Gian Paolo Rossi, MD, FAHA, FACC, University Hospital Padova

RAndomized Clinical Trial in COvid19 Patients to Assess the Efficacy of the Transmembrane Protease Serine 2 (TMPRSS2) Inhibitor NAfamostat (RACONA Study)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

256

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Padova, Italy, 35128
        • Recruiting
        • Azienda Ospedale Università di Padova
        • Contact:
          • Gian Paolo Rossi, Prof.
        • Sub-Investigator:
          • Andrea Vianello, MD
        • Sub-Investigator:
          • Gabriella Guarnieri, MD
        • Sub-Investigator:
          • Sara Lococo, MD
        • Sub-Investigator:
          • Beatrice Molena, BSc
        • Principal Investigator:
          • Paola Fioretto, MD
        • Sub-Investigator:
          • Filippo Farnia, MD
        • Sub-Investigator:
          • Federico Capone, MD
        • Principal Investigator:
          • Annamaria Cattelan, MD
        • Sub-Investigator:
          • Maria Mazzitelli, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Nafamostat
Nafamostat mesylate on top of best standard of care.
Drug: Nafamostat Mesilate
administered intravenously as a continuous infusion
Other Names:
  • no alternative name. Commercial brands are available.
Placebo Comparator: Placebo
Placebo on top of best standard of care.
Drug: Placebo
administered intravenously as a continuous infusion
Other Names:
  • no alternative name.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time-to-clinical improvement
Time Frame: day 1 until day 28
Time-to-clinical improvement (time from randomization to an improvement of two points (from the status at randomization) on a 7 category ordinal scale or live discharge from the hospital, whichever came first.
day 1 until day 28

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Responders
Time Frame: day 1 until day 28
Rate of patients showing improvement of 2 points in 7 category ordinal scale (with 7 points the worst)(PubMed ID: 32187464)
day 1 until day 28
Critical or dead patients
Time Frame: day 1 until day 28
Proportion of patients who will progress to critical illness/death
day 1 until day 28
pO2/FiO2 ratio
Time Frame: day 1 until day 28
Change in pO2/FiO2 ratio over time
day 1 until day 28
SOFA score over time
Time Frame: day 1 until day 28
Change Sequential organ failure assessment score (SOFA score) over time. The Score ranges from 0 to 24 (with 24 the worst)(PubMed ID: 11594901)
day 1 until day 28
Hospitalization
Time Frame: day 1 until day 28
Duration of hospitalization in survivors (days)
day 1 until day 28
Mechanical ventilation
Time Frame: day 1 until day 28
Number of patients who require ventilation
day 1 until day 28
Mechanical ventilation duration
Time Frame: day 1 until day 28
Duration of ventilation (days)
day 1 until day 28
Cardiovascular disease
Time Frame: day 1 until day 28
Proportion of patients who develop arrhythmia, or myocardial infarction, or other cardiovascular disease not present at the baseline
day 1 until day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Padova

Collaborators

University of Zurich
Yokohama City University

Investigators

  • Principal Investigator: Gian Paolo Rossi, Prof., University of Padova, Italy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 4, 2021

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

December 1, 2024

Study Registration Dates

First Submitted

April 3, 2020

First Submitted That Met QC Criteria

April 15, 2020

First Posted (Actual)

April 20, 2020

Study Record Updates

Last Update Posted (Actual)

November 1, 2023

Last Update Submitted That Met QC Criteria

October 31, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RACONA Nafamostat

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Study Data/Documents

  1. Individual Participant Data Set
    Information identifier: GPR (PI)
    Information comments: 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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on COVID19

Clinical Trials on Nafamostat Mesilate

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kenya

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe