Spironolactone and Dexamethasone in Patients Hospitalized With Moderate-to-severe COVID-19 (SPIDEX-II): a Randomized Clinical Trial
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 440
- 试验地点
- 1
- 主要终点
- Evaluation of the clinical status
研究概览
简要总结
The Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) is a rapidly spreading infection of the respiratory tract. Most infected patients have either asymptomatic disease or mild symptoms. However, a proportion of patients, especially elderly men or patients with comorbidities, are at risk of developing acute respiratory distress syndrome (ARDS). ARDS, alongside clotting abnormalities, is known to be a major contributor to SARS-CoV-2-related mortality and admission to intensive care units, with evidenced effective preventative treatment options lacking. In this study, the investigators test a novel hypothesis that the use of a combination of spironolactone and dexamethasone at low doses will improve the clinical progression of the infection evaluated by the 6-point ordinal scale in patients with moderate and severe disease by blocking exocytosis of the Weibel-Palade bodies from endothelial cells.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years or above;
- •Signed informed consent;
- •PCR-confirmed diagnosis of SARS-CoV-2 infection
- •Presenting with moderate-to-severe disease (scores 4-6 on WHO ordinal scale)
排除标准
- •Women of childbearing age without a negative urine pregnancy test, currently pregnant or breastfeeding women;
- •Severe heart failure (NYHA4), severe renal failure (eGFR < 30 ml/min/1.73 m2), severe liver failure (ALT/AST ratio > 5 norms), severe anemia (haemoglobin < 30 g/l)
- •Participating in another clinical trial
- •Severe electrolyte imbalance (hyperkalemia > 5.0 mmol/l, hyponatremia < 120 mmol/l)
- •Hypersensitivity or contraindications to the study drugs (spironolactone and dexamethasone)
- •Renal dialysis
- •Severe uncontrolled diabetes mellitus
- •Patient receiving one of the following medications that cannot be substituted over the trial duration: ACE inhibitors, amiloride, eplerenone, cortisone acetate, potassium canrenoate, triamterene
研究组 & 干预措施
Treatment
After randomisation (Day 1): Spironolactone [100 mg 1x/day] + dexamethasone [2 mg 2x/day, 12/12h] Days 2-12*: Spironolactone [50 mg 2x/day, 12/12h] + dexamethasone [2 mg 2x/day, 12/12h] Days 13-20: Spironolactone [25 mg 2x/day, 12/12h] Days 21-28: Spironolactone [25 mg 1x/day] Standard treatment is according to the treatment protocol for 2019-nCoV infection.
*In case of cortisol levels above 100 nmol/L on days 3 and 4, the dexamethasone dose should be increased to 3 mg in the morning and in the evening (total 6 mg per day).
干预措施: Spironolactone + Dexamethasone (Drug)
Control
Patients receiving standard-of-care treatment for SARS-CoV-2 infection as regulated by the relevant guidelines of the Ministry of Healthcare of the Russian Federation
干预措施: Standard-of-care SARS-CoV-2 treatment (Drug)
结局指标
主要结局
Evaluation of the clinical status
时间窗: Day 14 post-randomization
Clinical status at day 14 post-randomization defined by a 6-point ordinal scale score (6 being the worst score)
次要结局
- 28-day all-cause mortality(28 days post-randomization)
- Oxygen-free days(28 days post-randomization)
- Invasive mechanical ventilation(28 days post-randomization)
- Ventilator-free days(28 days post-randomization)
- Time to discharge(28 days post-randomization)
- Length of ICU stay(28 days post-randomization)
- New ICU admission(28 days post-randomization)
- Long-COVID development(60 and 90 days post-admission)
- Evaluation of the clinical status(Day 7 post-randomization)