Testing nafamostat for treating COVID-19 patients

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

This study is testing if a medication called nafamostat can help hospitalized COVID-19 patients recover faster and avoid needing intensive care.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 256 (estimated)
• Ages: 18 Years to 85 Years
• Sex: All
• Sponsor: University Hospital Padova (Academic / other)
• Locations: 1 site (Padova)
• Trial ID: NCT04352400 on ClinicalTrials.gov

What this trial studies

The RACONA trial is a prospective, double-blind, randomized, placebo-controlled study aimed at evaluating the efficacy of nafamostat mesylate in hospitalized COVID-19 patients. Participants will receive either nafamostat or a placebo in addition to the best standard of care. The primary outcome measure is the time to clinical improvement, defined as a two-point improvement on a seven-category ordinal scale or live discharge from the hospital. The study hypothesizes that nafamostat can reduce lung function deterioration and the need for intensive care by targeting the protease TMPRSS2, which plays a role in SARS-CoV-2 cell entry.

Who should consider this trial

Good fit: Ideal candidates are hospitalized adults aged 18 to 85 who are COVID-19 positive and meet specific respiratory and oxygenation criteria.

Not a fit: Patients who are pregnant, have rapidly deteriorating conditions, or severe liver disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve lung function and reduce the need for intensive care in COVID-19 patients.

How similar studies have performed: Other studies have explored protease inhibitors for COVID-19, but the specific use of nafamostat in this context is novel.

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.

Where this trial is running

Padova

• Azienda Ospedale Università di Padova — Padova, Italy (Recruiting)

Study contacts

• Principal investigator: Gian Paolo Rossi, Prof. — University of Padova, Italy
• Study coordinator: Gian Paolo Rossi, Prof.

Conditions COVID19; Nafamostat; proteases; TMPRSS2; covid-19; coronavirus