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

RACONA Nafamostat

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.

2021-06-04

2024-12-01

2024-12-01

Recruiting

Early phase I

256

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.

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2023-11-01