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

• Status: Recruiting
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital Padova
• Collaborators: University of Zurich; Yokohama City University
• Treatments: Nafamostat

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.