A Multicenter, Randomized, Active Controlled, Open Label, Platform Trial on the Efficacy and Safety of Experimental Therapeutics for Patients With COVID-19 (Caused by Infection With Severe Acute Respiratory Syndrome Coronavirus-2)
试验速览
- 阶段
- 2 期
- 入组人数
- 500
- 试验地点
- 9
- 主要终点
- sustained improvement (>48h) of one point on the WHO Scale
研究概览
简要总结
The Austrian Coronavirus Adaptive Clinical Trial (ACOVACT) is a randomized, controlled, multicenter, open-label basket trial that aims to compare various antiviral treatments for COVID-19. Moreover three substudies have been integrated. Currently, patients will be randomized to receive (hydroxy-)chloroquine (Treatment stopped after reports of safety issues), lopinavir/ritonavir, remdesivir or standard of care. Moreover, these patients are eligible for substudy A (randomized to rivaroxaban 5mg 1-0-1 vs. standard of care), substudy B (renin-angiotensin (RAS) blockade vs. no RAS blockade for patients with blood pressure >120/80mmHg), and substudy C (asunercept vs standard of care, pentglobin vs. standard of care for patients with respiratory deterioration and high inflammatory biomarkers).
Endpoints were chosen based on the master protocol published by the World Health Organisation and include a 7-point scale of clinical performance, mortality, oxygen requirement (both dose and type), duration of hospitalization, viral load and safety.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Asunercept 400mg
400mg 1x per week, maximum of four doses only patients with oxygen requirement
干预措施: Asunercept 400mg (Drug)
Best Standard of Care - Control Group for Asunercept
only patients with oxygen requirement
干预措施: Best standard of care (Other)
(Hydroxy)Chloroquine (STOPPED)
Due to limited availability of the experimental substances, this arm will include both chloroquine and hydroxychloroquine treatment. However, both substances are similar chemically and also with regards to the mechanism of action comparable.
Dosage: Hydroxychloroquine 200mg 2-0-2 on day 1 followed by 200mg 1-0-1, or Chloroquine 250mg 2-0-2, as available
干预措施: Chloroquine or Hydroxychloroquine (Drug)
Lopinavir/Ritonavir
Dosage: 200mg/50mg 4-0-4 on day 1 and 3-0-3 thereafter
干预措施: Lopinavir/Ritonavir (Drug)
Standard of Care
patients will be treated with "standard of care", which precludes treatment with lopinavir/ritonavir or (hydroxy-)chloroquine
干预措施: Best standard of care (Other)
Rivaroxaban
5mg 1-0-1
干预措施: Rivaroxaban (Drug)
Thromboprophylaxis
according to local standard
干预措施: Thromboprophylaxis (Drug)
Remdesivir
200mg loading dose on day 1, 100mg for a total treatment duration of 5-10 days
干预措施: Remdesivir (Drug)
RAS Blockade
Renin-Angiotensin-System-Blockade (RAS) by candesartan intake starting with 4mg once daily and titrated to normotension patients > 120/80 mmHG are eligible
干预措施: Candesartan (Drug)
non-RAS-Blockade
non-RAS blocking antihypertensive agents titrated to normotension Those with normal blood pressure may only be controlled without further treatment
干预措施: non-RAS blocking antihypertensives (Drug)
Asunercept 25mg
25mg 1x per week, maximum of four doses only patients with oxygen requirement
干预措施: Asunercept 25mg (Drug)
Asunercept 100mg
100mg 1x per week, maximum of four doses only patients with oxygen requirement
干预措施: Asunercept 100mg (Drug)
Pentaglobin
Patients treated at the intensive care unit only, continuous infusion of 7ml/kg/day over 12h for 5 days
干预措施: Pentaglobin (Drug)
best standard of care
Patients treated at the intensive care unit only
干预措施: Best standard of care (Other)
结局指标
主要结局
sustained improvement (>48h) of one point on the WHO Scale
时间窗: Inclusion to day 29, daily evaluation
The primary endpoint is time to clinical improvement which is defined as time from randomization to an (sustained) improvement of at least one category on two consecutive days compared to the status at randomization measured on a seven-category ordinal scale (proposed by WHO). The 7-categories of the World Health Organization proposed scale, as follows: 1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities; 3. Hospitalized, not requiring supplemental oxygen; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6. Hospitalized, on invasive mechanical ventilation or ECMO; 7. Death. During hospitalization this score will be determined daily (till day 29). If a patient is released from the hospital before day 29, the score will be determined at day 11 and 29 after randomization (depending when the patient was released or by telephone call).
次要结局
- Obesity - mortality(BMI at admission, mortality until day 29)
- modified Sequential Organ Failure Assessment(Inclusion to day 29, daily evaluation)
- C-reactive protein(baseline, day 2, 3, 4, 5, 7)
- Time to improvement on WHO Scale(Inclusion to day 29, daily evaluation)
- Oxygenation free days(Inclusion to day 29, daily evaluation)
- Duration of Hospitalization(Inclusion to day 29, daily evaluation)
- Mortality(15-day, 29-day, 60-day, 90-day mortality)
- Obesity - new oxygen use(BMI at admission, new oxygen use until day 29 or discharge)
- Renin Angiotensin System (RAS) fingerprint(Inclusion to day 29, daily evaluation)
- time to discharge or a National Early Warning Score (NEWS) ≤2 (maintained for 24h), whichever occurs first(Inclusion to day 29, daily evaluation)
- change from baseline in National Early Warning Score (NEWS)(Inclusion to day 29, daily evaluation)
- Incidence of new oxygen use during the trial(Inclusion to day 29, daily evaluation)
- Incidence of new mechanical ventilation use during the trial(Inclusion to day 29, daily evaluation)
- Drug-drug interactions with lopinavir/ritonavir(Inclusion to day 29, daily evaluation)
- paO/FiO2 ratio(Inclusion to day 29, daily evaluation)
- IgA Concentrations(baseline, day 2, 3, 4, 5, 7)
- Mean change in the ranking on an ordinal scale from baseline(Inclusion to day 29, daily evaluation)
- duration of oxygen use during the trial(Inclusion to day 29, daily evaluation)
- Ventilator free days until day 29(Inclusion to day 29, daily evaluation)
- Viral load/viral clearance(Inclusion to day 29, daily evaluation)
- IgM Concentrations(baseline, day 2, 3, 4, 5, 7)
- differential blood counts(baseline, day 2, 3, 4, 5, 7)
- duration of mechanical ventilation use during the trial(Inclusion to day 29, daily evaluation)
- Obesity - duration of hospitalization(BMI at admission, duration of hospitalization until day 29 or discharge)
- Obesity - ICU admission(BMI at admission, ICU admission until day 29 or discharge)
- SpO2/FiO2 ratio(Inclusion to day 29, daily evaluation)
- Interleukin-6(baseline, day 2, 3, 4, 5, 7)
- procalcitonin(baseline, day 2, 3, 4, 5, 7)
研究者
Bernd Jilma
Univ.Prof.Dr. Bernd Jilma
Medical University of Vienna