RAndomized Clinical Trial in COvid19 Patients to Assess the Efficacy of the Transmembrane Protease Serine 2 (TMPRSS2) Inhibitor NAfamostat (RACONA Study)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 256
- 试验地点
- 1
- 主要终点
- Time-to-clinical improvement
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Randomization will be done with an algorithm tailored to the study design. Investigators and patients will be blinded to the treatment administered.
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Nafamostat
Nafamostat mesylate on top of best standard of care.
干预措施: Nafamostat Mesilate (Drug)
Placebo
Placebo on top of best standard of care.
干预措施: Placebo (Drug)
结局指标
主要结局
Time-to-clinical improvement
时间窗: 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.
次要结局
- pO2/FiO2 ratio(day 1 until day 28)
- Critical or dead patients(day 1 until day 28)
- Responders(day 1 until day 28)
- Hospitalization(day 1 until day 28)
- Mechanical ventilation duration(day 1 until day 28)
- Cardiovascular disease(day 1 until day 28)
- SOFA score over time(day 1 until day 28)
- Mechanical ventilation(day 1 until day 28)
研究者
Gian Paolo Rossi, MD, FAHA, FACC
Prof.
University Hospital Padova