NCT04352400.

Study name	RAndomized clinical trial in COvid19 patients to assess the efficacy of the transmembrane protease serine 2 (TMPRSS2) inhibitor NAfamostat (RACONA Study)
Starting date	1 April 2020
Contact information	Gian Paolo Rossi University Hospital Padova, Italy 00390498217821 | gianpaolo.rossi@unipd.it
Methods	Multicentre, double‐blind, 2‐armed, parallel‐assignment RCT
Participants	256 participants, 18‐85 years, female and male Inclusion criteria Hospitalized, COVID‐19‐positive, between 18 and ≤ 85 years of age Signed informed consent form Body temperature > 37.3 °C Oxygenation criterion (any of the following): oxygen saturation ≤ 94% on room air PaO2/FiO2 ratio ≤ 300 mmHg but > 100 mmHg, if participant on supplemental oxygen SpO2/FiO2 < 200 if no arterial blood gas available Respiratory rate (RR) ≥ 25 breaths/min Exclusion criteria Pregnant or lactating women 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) participants 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 HIT Unstable haemodynamics in the preceding 4 h (SBP < 90 mmHg, and/or vasoactive agents required) Haemoglobin < 7 at time of drug infusion. Transfusion is allowed to increase haemoglobin levels before entry into the study Malignancy or any other condition for which estimated 6‐month mortality > 50% Arterial blood pH < 7.2 Known evidence of chronic interstitial infiltration at imaging Known hospitalisation within the past 6 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 polycythaemia, severe pulmonary hypertension, or ventilator dependency Known vasculitis with diffuse alveolar haemorrhage Pre‐existing renal failure on haemodialysis or peritoneal dialysis requiring renal replacement therapy ECMO Immunosuppressive treatment Participant in studies for COVID‐19 within 30 days before Unstable haemodynamics in the preceding 4 h (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
Interventions	Experimental: nafamostat mesilate, administered IV as a continuous infusion Comparator: placebo, administered IV as a continuous infusion
Outcomes	Primary Time‐to‐clinical improvement (time frame: day 1 until day 28). Time‐to‐clinical improvement (time from randomisation to an improvement of 2 points (from the status at randomisation) on a 7‐category ordinal scale or live discharge from the hospital, whichever came first Secondary Responders (time frame: day 1 until day 28). Rate of participants showing improvement of 2 points in 7‐category ordinal scale (with 7 points the worst) (PubMed ID: 32187464) Critical or dead participants (time frame: day 1 until day 28). Proportion of participants who will progress to critical illness/death pO2/FiO2 ratio (time frame: day 1 until day 28). Change in pO2/FiO2 ratio over time SOFA score over time (time frame: day 1 until day 28). Change SOFA score over time. The score ranges from 0‐24 (with 24 the worst) (PubMed ID: 11594901) Hospitalisation (time frame: day 1 until day 28) Duration of hospitalisation in survivors (days) Mechanical ventilation (time frame: day 1 until day 28). Number of participants who require ventilation Mechanical ventilation duration (time frame: day 1 until day 28). Duration of ventilation (days) Cardiovascular disease (time frame: day 1 until day 28). Proportion of participants who develop arrhythmia, or myocardial infarction, or other cardiovascular disease not present at the baseline
Notes	NCT04352400 | No data provided