Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- UMC Utrecht
- 入组人数
- 20,000
- 试验地点
- 408
- 主要终点
- All-cause mortality
研究概览
简要总结
REMAP-CAP is a randomised, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia.
The purpose of this study is to evaluate the effect of a range of interventions to improve outcome of patients admitted to intensive care with community-acquired pneumonia.
In addition, REMAP-CAP provides and adaptive research platform for evaluation of multiple treatment modalities in the event of a respiratory pandemic such as COVID-19.
REMAP-COVID is a sub-platform of REMAP-CAP that evaluates treatments specific to COVID-19 in the United States of America.
详细描述
Community-acquired pneumonia (CAP) that is of sufficient severity to require admission to an intensive care unit (ICU) is associated with substantial mortality.
Patients with pneumonia who are being treated in an ICU will receive therapy that consists of many different treatments, as many as 20 or 30. These treatments act together to treat both the infection and its effects on the body. When treating a patient, doctors choose from many different treatments, most of which are known or believed to be safe and effective. However, doctors don't always know which treatment option is the better one, as individuals or groups of individuals may respond differently. This study aims to help doctors understand which treatments work best.
This clinical study has been designed in a way that allows the information from patients already in the study to help new patients joining the study. Most studies aren't able to do that. REMAP-CAP has been designed to:
- Evaluate multiple treatment strategies, at the same time, in the same patient.
- Reach platform conclusions when sufficient data is accrued, rather than when a pre-specified sample size is reached
- Utilise data that is already accrued to increase the likelihood that patients within the trial are randomised to treatments that are more likely to be beneficial
- New questions can be substituted into the trial as initial questions are answered, meaning that the trial can be perpetual or open-ended
- Interactions between interventions in different domains can be evaluated
It is reasonable to presume that any pandemic respiratory infection of major significance to public health will manifest as life-threatening respiratory infection including Severe Acute Respiratory illness and severe Community Acquired Pneumonia (CAP) with concomitant admission to hospital, and for some patients, admission to an Intensive Care Unit (ICU). Previous pandemics and more localized outbreaks of respiratory emerging infections have resulted in severe CAP and ICU admission.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Antibiotic Domain
Patients with community-acquired pneumonia admitted to participating intensive care units and requiring empiric antibiotic therapy will be randomised one of five antibiotic interventions.
Note: the ceftaroline + macrolide intervention has been closed to recruitment.
干预措施: Ceftriaxone (Drug)
Antibiotic Domain
Patients with community-acquired pneumonia admitted to participating intensive care units and requiring empiric antibiotic therapy will be randomised one of five antibiotic interventions.
Note: the ceftaroline + macrolide intervention has been closed to recruitment.
干预措施: Moxifloxacin or Levofloxacin (Drug)
Antibiotic Domain
Patients with community-acquired pneumonia admitted to participating intensive care units and requiring empiric antibiotic therapy will be randomised one of five antibiotic interventions.
Note: the ceftaroline + macrolide intervention has been closed to recruitment.
干预措施: Piperacillin-tazobactam (Drug)
Antibiotic Domain
Patients with community-acquired pneumonia admitted to participating intensive care units and requiring empiric antibiotic therapy will be randomised one of five antibiotic interventions.
Note: the ceftaroline + macrolide intervention has been closed to recruitment.
干预措施: Ceftaroline (Drug)
Antibiotic Domain
Patients with community-acquired pneumonia admitted to participating intensive care units and requiring empiric antibiotic therapy will be randomised one of five antibiotic interventions.
Note: the ceftaroline + macrolide intervention has been closed to recruitment.
干预措施: Amoxicillin-clavulanate (Drug)
Macrolide Duration Domain
Patients with community-acquired pneumonia admitted to participating intensive care units who have been allocated to a beta-lactam antibiotic intervention in the Antibiotic Domain will be randomised to either a standard course or extended course of macrolide therapy
干预措施: Standard course macrolide (Drug)
Macrolide Duration Domain
Patients with community-acquired pneumonia admitted to participating intensive care units who have been allocated to a beta-lactam antibiotic intervention in the Antibiotic Domain will be randomised to either a standard course or extended course of macrolide therapy
干预措施: Extended course macrolide (Drug)
Corticosteroid Domain
Patients with community acquired pneumonia (CAP) admitted to participating hospitals will be randomised to a steroid use strategy.
Note: this domain is now closed to patients with suspected or proven COVID-19. It remains open to patients with CAP without COVID-19.
Note: the fixed-course hydrocortisone has been closed to recruitment
干预措施: No systemic corticosteroid (Other)
Corticosteroid Domain
Patients with community acquired pneumonia (CAP) admitted to participating hospitals will be randomised to a steroid use strategy.
Note: this domain is now closed to patients with suspected or proven COVID-19. It remains open to patients with CAP without COVID-19.
Note: the fixed-course hydrocortisone has been closed to recruitment
干预措施: Fixed-duration Hydrocortisone (Drug)
Corticosteroid Domain
Patients with community acquired pneumonia (CAP) admitted to participating hospitals will be randomised to a steroid use strategy.
Note: this domain is now closed to patients with suspected or proven COVID-19. It remains open to patients with CAP without COVID-19.
Note: the fixed-course hydrocortisone has been closed to recruitment
干预措施: Shock-dependent hydrocortisone (Drug)
Corticosteroid Domain
Patients with community acquired pneumonia (CAP) admitted to participating hospitals will be randomised to a steroid use strategy.
Note: this domain is now closed to patients with suspected or proven COVID-19. It remains open to patients with CAP without COVID-19.
Note: the fixed-course hydrocortisone has been closed to recruitment
干预措施: Fixed-duration higher dose Hydrocortisone (Drug)
Corticosteroid Domain
Patients with community acquired pneumonia (CAP) admitted to participating hospitals will be randomised to a steroid use strategy.
Note: this domain is now closed to patients with suspected or proven COVID-19. It remains open to patients with CAP without COVID-19.
Note: the fixed-course hydrocortisone has been closed to recruitment
干预措施: Fixed-duration dexamethasone (Drug)
Influenza Antiviral Domain
Patients with community-acquired pneumonia admitted to participating hospitals with microbiological testing confirmed influenza infection will be randomised to one of six interventions.
干预措施: No antiviral agent for influenza (Other)
Influenza Antiviral Domain
Patients with community-acquired pneumonia admitted to participating hospitals with microbiological testing confirmed influenza infection will be randomised to one of six interventions.
干预措施: Five-days oseltamivir (Drug)
Influenza Antiviral Domain
Patients with community-acquired pneumonia admitted to participating hospitals with microbiological testing confirmed influenza infection will be randomised to one of six interventions.
干预措施: Ten-days oseltamivir (Drug)
Influenza Antiviral Domain
Patients with community-acquired pneumonia admitted to participating hospitals with microbiological testing confirmed influenza infection will be randomised to one of six interventions.
干预措施: Baloxavir Marboxil (Drug)
Influenza Antiviral Domain
Patients with community-acquired pneumonia admitted to participating hospitals with microbiological testing confirmed influenza infection will be randomised to one of six interventions.
干预措施: Five-days oseltamivir + baloxavir marboxil (Drug)
Influenza Antiviral Domain
Patients with community-acquired pneumonia admitted to participating hospitals with microbiological testing confirmed influenza infection will be randomised to one of six interventions.
干预措施: Ten-days oseltamivir + baloxavir marboxil (Drug)
COVID-19 Antiviral Domain
Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to no ivermectin or ivermectin.
Note: an earlier version of this domain evaluated lopinavir-ritonavir, hydroxychloroquine, and combination lopinavir-ritonavir and hydroxychloroquine against a 'no antiviral' control.
This domain is now closed.
干预措施: No antiviral agent for COVID-19 (Other)
COVID-19 Antiviral Domain
Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to no ivermectin or ivermectin.
Note: an earlier version of this domain evaluated lopinavir-ritonavir, hydroxychloroquine, and combination lopinavir-ritonavir and hydroxychloroquine against a 'no antiviral' control.
This domain is now closed.
干预措施: Lopinavir / Ritonavir (Drug)
COVID-19 Antiviral Domain
Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to no ivermectin or ivermectin.
Note: an earlier version of this domain evaluated lopinavir-ritonavir, hydroxychloroquine, and combination lopinavir-ritonavir and hydroxychloroquine against a 'no antiviral' control.
This domain is now closed.
干预措施: Hydroxychloroquine (Drug)
COVID-19 Antiviral Domain
Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to no ivermectin or ivermectin.
Note: an earlier version of this domain evaluated lopinavir-ritonavir, hydroxychloroquine, and combination lopinavir-ritonavir and hydroxychloroquine against a 'no antiviral' control.
This domain is now closed.
干预措施: Hydroxychloroquine + lopinavir/ritonavir (Drug)
COVID-19 Antiviral Domain
Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to no ivermectin or ivermectin.
Note: an earlier version of this domain evaluated lopinavir-ritonavir, hydroxychloroquine, and combination lopinavir-ritonavir and hydroxychloroquine against a 'no antiviral' control.
This domain is now closed.
干预措施: Ivermectin (Drug)
COVID-19 Immune Modulation Domain
Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to one of up to five interventions.
Note: this domain is now closed.
干预措施: No immune modulation for COVID-19 (Other)
COVID-19 Immune Modulation Domain
Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to one of up to five interventions.
Note: this domain is now closed.
干预措施: Interferon beta-1a (Drug)
COVID-19 Immune Modulation Domain
Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to one of up to five interventions.
Note: this domain is now closed.
干预措施: Anakinra (Drug)
COVID-19 Immune Modulation Domain
Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to one of up to five interventions.
Note: this domain is now closed.
干预措施: Tocilizumab (Drug)
COVID-19 Immune Modulation Domain
Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to one of up to five interventions.
Note: this domain is now closed.
干预措施: Sarilumab (Drug)
Anticoagulation Domain
Patients admitted to participating intensive care units with suspected or microbiological testing confirmed COVID-19 will be randomised to an anticoagulation strategy.
Note: A previous version of this domain evaluated local standard venous thromboprophylaxis against therapeutic dose anticoagulation. This domain is now closed.
干预措施: Local standard venous thromboprophylaxis (Drug)
Anticoagulation Domain
Patients admitted to participating intensive care units with suspected or microbiological testing confirmed COVID-19 will be randomised to an anticoagulation strategy.
Note: A previous version of this domain evaluated local standard venous thromboprophylaxis against therapeutic dose anticoagulation. This domain is now closed.
干预措施: Therapeutic dose anticoagulation (Drug)
Anticoagulation Domain
Patients admitted to participating intensive care units with suspected or microbiological testing confirmed COVID-19 will be randomised to an anticoagulation strategy.
Note: A previous version of this domain evaluated local standard venous thromboprophylaxis against therapeutic dose anticoagulation. This domain is now closed.
干预措施: Conventional low dose thromboprophylaxis (Drug)
Anticoagulation Domain
Patients admitted to participating intensive care units with suspected or microbiological testing confirmed COVID-19 will be randomised to an anticoagulation strategy.
Note: A previous version of this domain evaluated local standard venous thromboprophylaxis against therapeutic dose anticoagulation. This domain is now closed.
干预措施: Intermediate dose thromboprophylaxis (Drug)
Anticoagulation Domain
Patients admitted to participating intensive care units with suspected or microbiological testing confirmed COVID-19 will be randomised to an anticoagulation strategy.
Note: A previous version of this domain evaluated local standard venous thromboprophylaxis against therapeutic dose anticoagulation. This domain is now closed.
干预措施: Continuation of therapeutic dose anticoagulation (Drug)
Immunoglobulin Domain
Immunosuppressed patients admitted to participating hospitals with microbiological testing confirmed COVID-19 will be randomised to receive no immunoglobulin for COVID-19, or to receive high-titre convalescent plasma.
Note: an earlier version of this domain was not restricted to immunosuppressed patients.
干预措施: No immunoglobulin (Other)
Immunoglobulin Domain
Immunosuppressed patients admitted to participating hospitals with microbiological testing confirmed COVID-19 will be randomised to receive no immunoglobulin for COVID-19, or to receive high-titre convalescent plasma.
Note: an earlier version of this domain was not restricted to immunosuppressed patients.
干预措施: Convalescent plasma (Biological)
Immunoglobulin Domain
Immunosuppressed patients admitted to participating hospitals with microbiological testing confirmed COVID-19 will be randomised to receive no immunoglobulin for COVID-19, or to receive high-titre convalescent plasma.
Note: an earlier version of this domain was not restricted to immunosuppressed patients.
干预措施: Delayed administration of convalescent plasma (Biological)
Vitamin C Domain
Patients admitted to participating hospitals with community-acquired pneumonia will be randomised to receive no vitamin C, or vitamin C.
Note: this domain is now closed.
干预措施: No vitamin C (Other)
Vitamin C Domain
Patients admitted to participating hospitals with community-acquired pneumonia will be randomised to receive no vitamin C, or vitamin C.
Note: this domain is now closed.
干预措施: Vitamin C (Drug)
Simvastatin Domain
Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to receive no simvastatin, or simvastatin.
Note: this domain is now closed.
干预措施: No simvastatin (Other)
Simvastatin Domain
Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to receive no simvastatin, or simvastatin.
Note: this domain is now closed.
干预措施: Simvastatin (Drug)
Antiplatelet Domain
Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to receive no antiplatelet, aspirin, or site-preferred P2Y12 inhibitor.
Note: this domain is now closed.
干预措施: No antiplatelet (Other)
Antiplatelet Domain
Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to receive no antiplatelet, aspirin, or site-preferred P2Y12 inhibitor.
Note: this domain is now closed.
干预措施: Aspirin (Drug)
Antiplatelet Domain
Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to receive no antiplatelet, aspirin, or site-preferred P2Y12 inhibitor.
Note: this domain is now closed.
干预措施: P2Y12 inhibitor (Drug)
Mechanical Ventilation Domain
Patients with community-acquired pneumonia admitted to participating intensive care units who are intubated and receiving invasive mechanical ventilation will be randomised to protocolised mechanical ventilation strategy, or clinician-preferred mechanical ventilation strategy
干预措施: Clinician-preferred mechanical ventilation strategy (Procedure)
Mechanical Ventilation Domain
Patients with community-acquired pneumonia admitted to participating intensive care units who are intubated and receiving invasive mechanical ventilation will be randomised to protocolised mechanical ventilation strategy, or clinician-preferred mechanical ventilation strategy
干预措施: Protocolised mechanical ventilation strategy (Procedure)
COVID-19 Immune Modulation (2) Domain
Patients admitted to participating hospitals with microbiological testing confirmed COVID-19 will be randomised to receive one of three interventions.
Note: this domain is now closed.
干预措施: No immune modulation for COVID-19 (Other)
COVID-19 Immune Modulation (2) Domain
Patients admitted to participating hospitals with microbiological testing confirmed COVID-19 will be randomised to receive one of three interventions.
Note: this domain is now closed.
干预措施: Eritoran (Drug)
ACE2 RAS Domain
Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to one of up to five renin-angiotensin system blockade strategies.
Note: this domain is now closed.
干预措施: Angiotensin Receptor Blockers (Drug)
COVID-19 Immune Modulation (2) Domain
Patients admitted to participating hospitals with microbiological testing confirmed COVID-19 will be randomised to receive one of three interventions.
Note: this domain is now closed.
干预措施: Apremilast (Drug)
ACE2 RAS Domain
Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to one of up to five renin-angiotensin system blockade strategies.
Note: this domain is now closed.
干预措施: No renin-angiotensin system inhibitor (Other)
ACE2 RAS Domain
Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to one of up to five renin-angiotensin system blockade strategies.
Note: this domain is now closed.
干预措施: Angiotensin converting enzyme inhibitor (Drug)
ACE2 RAS Domain
Patients admitted to participating hospitals with suspected or microbiological testing confirmed COVID-19 will be randomised to one of up to five renin-angiotensin system blockade strategies.
Note: this domain is now closed.
干预措施: ARB + DMX-200 (Drug)
Cysteamine Domain
Patients admitted to participating hospitals with severe community-acquired pneumonia, including patients with suspected or proven influenza or COVID-19, will be randomised to receive no cysteamine, or cysteamine.
Note: this domain is now closed.
干预措施: No cysteamine (Other)
Cysteamine Domain
Patients admitted to participating hospitals with severe community-acquired pneumonia, including patients with suspected or proven influenza or COVID-19, will be randomised to receive no cysteamine, or cysteamine.
Note: this domain is now closed.
干预措施: Cysteamine (Drug)
Endothelial Domain
Patients admitted to participating hospitals with severe community-acquired pneumonia, including patients with suspected or proven influenza or COVID-19, will be randomised to receive no endothelial modulator or enteral imatinib.
干预措施: No endothelial modulator (Other)
Endothelial Domain
Patients admitted to participating hospitals with severe community-acquired pneumonia, including patients with suspected or proven influenza or COVID-19, will be randomised to receive no endothelial modulator or enteral imatinib.
干预措施: Imatinib (Drug)
Influenza Immune Modulation
Patients with community-acquired pneumonia admitted to participating intensive care units with microbiological testing confirmed influenza infection will be randomised to one of three interventions.
干预措施: No Immune Modulator for Influenza (Other)
Influenza Immune Modulation
Patients with community-acquired pneumonia admitted to participating intensive care units with microbiological testing confirmed influenza infection will be randomised to one of three interventions.
干预措施: Tocilizumab (Drug)
Influenza Immune Modulation
Patients with community-acquired pneumonia admitted to participating intensive care units with microbiological testing confirmed influenza infection will be randomised to one of three interventions.
干预措施: Baricitinib (Drug)
COVID-19 Antiviral (II) Domain
Patients admitted to participating hospitals with microbiological testing confirmed COVID-19 will be randomised to one of up to four interventions.
干预措施: No antiviral agent for COVID-19 (Other)
COVID-19 Antiviral (II) Domain
Patients admitted to participating hospitals with microbiological testing confirmed COVID-19 will be randomised to one of up to four interventions.
干预措施: Nirmatrelvir/ritonavir (Drug)
COVID-19 Antiviral (II) Domain
Patients admitted to participating hospitals with microbiological testing confirmed COVID-19 will be randomised to one of up to four interventions.
干预措施: Remdesivir (Drug)
COVID-19 Antiviral (II) Domain
Patients admitted to participating hospitals with microbiological testing confirmed COVID-19 will be randomised to one of up to four interventions.
干预措施: Nirmatrelvir/ritonavir + remdesivir (Drug)
结局指标
主要结局
All-cause mortality
时间窗: Day 90
Days alive and not receiving organ support in ICU
时间窗: Day 21
Primary end-point for patients with suspected or proven COVID-19 pandemic infection
次要结局
- Hospital length of stay(Day 90)
- Ventilator free days(Day 28)
- World Health Organisation 8-point ordinal scale outcome(Hospital discharge)
- Organ failure free days(Day 28)
- All-cause mortality(6 months)
- Destination at time of hospital discharge(Free text Day 90)
- Proportion of intubated patients who receive a tracheostomy(Day 28)
- ICU length of stay(Day 90)
- Readmission to the index ICU during the index hospitalization(Day 90)
- ICU Mortality(Day 90)
- Health-related Quality of life assessment(6 months)