Randomised Evaluation of COVID-19 Therapy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 70,000
- 试验地点
- 18
- 主要终点
- All-cause mortality
研究概览
简要总结
RECOVERY is a randomised trial of treatments to prevent death in patients hospitalised with pneumonia.
The treatments being investigated are:
COVID-19: Lopinavir-Ritonavir, Hydroxychloroquine, Corticosteroids, Azithromycin, Colchicine, IV Immunoglobulin (children only), Convalescent plasma, Casirivimab+Imdevimab, Tocilizumab, Aspirin, Baricitinib, Empagliflozin, Sotrovimab, Molnupiravir, Paxlovid or Anakinra (children only)
Influenza: Baloxavir marboxil, Oseltamivir, Corticosteroids (dexamethasone)
Community-acquired pneumonia: Corticosteroids (dexamethasone)
详细描述
The RECOVERY trial has already shown that:
- Dexamethasone (a type of steroid) reduces the risk of dying for patients hospitalised with COVID-19 receiving oxygen.
- Regeneron's monoclonal antibody combination reduces deaths for hospitalised COVID-19 patients who have not mounted their own immune response.
- Tocilizumab reduces the risk of death when given to hospitalised patients with severe COVID-19. It also shortens the time until patients are successfully discharged from hospital and reduces the need for a mechanical ventilator.
- Baricitinib reduces the risk of death when given to hospitalised patients with severe COVID-19.
- In patients hospitalised for COVID-19 with clinical hypoxia but requiring either no oxygen or simple oxygen only, higher dose corticosteroids significantly increased the risk of death compared to usual care, which included low dose corticosteroids.
- Sotrovimab reduces the risk of death in some patients (specifically those with higher levels of the virus in their blood) hospitalised with COVID-19.
- In patients hospitalised with COVID-19, dexamethasone (at a dose of 6mg daily in hypoxic patients), tocilizumab (in hypoxic patients with CRP ≥75 mg/L), baricitinib, casirivimab-imdevimab (in seronegative patients), and sotrovimab (in high antigen patients) reduced 6-month mortality. Dexamethasone at a dose of 6mg daily was associated with an increase in major non-COVID infection but there was no evidence of other later emerging harms. Other treatments tested in RECOVERY did not reduce 6-month mortality.
The trial also concluded that there is no beneficial effect of hydroxychloroquine, lopinavir-ritonavir, azithromycin, convalescent plasma, colchicine, aspirin, dimethyl fumarate, empagliflozin, molnupiravir, or paxlovid in patients hospitalised with COVID-19, and these arms have been closed to recruitment with results reported.
BACKGROUND: In early 2020, as the RECOVERY Trial was being set-up, there were no approved treatments for COVID-19, a disease induced by the novel coronavirus SARSCoV-2 that emerged in China in late 2019. Opening in March 2020, RECOVERY evaluated twenty SARS-CoV-2 therapies, providing reliable evidence about their efficacy and safety that has informed the treatment of patients worldwide.
Since then, the progress in COVID-19 treatment has highlighted the need for better evidence for the treatment of pneumonia caused by other pathogens, such as influenza and bacteria, for which therapies are widely used without good evidence of benefit or safety.
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
- 0 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eligibility Criteria (as per Protocol v28.0):
- •Patients are eligible for the study if all of the following are true:
- •(i) Hospitalised
- •(ii) Pneumonia syndrome
- •In general, pneumonia should be suspected when a patient presents with:
- •typical symptoms of a new respiratory tract infection (e.g. influenza-like illness with fever and muscle pain, or respiratory illness with cough and shortness of breath); and
- •objective evidence of acute lung disease (e.g. consolidation or ground-glass shadowing on X-ray or CT, hypoxia, or compatible clinical examination); and
- •alternative causes have been considered unlikely or excluded (e.g. heart failure).
- •However, the diagnosis remains a clinical one based on the opinion of the managing doctor (the above criteria are just a guide).
- •(iii) One of the following diagnoses:
- •Confirmed influenza A or B infection (including patients with SARS-CoV-2 co-infection)
- •Community-acquired pneumonia (CAP) with planned antibiotic treatment (excluding patients with suspected or confirmed SARS-CoV-2, influenza, active pulmonary tuberculosis or Pneumocystis jirovecii pneumonia)
- •(iv) No medical history that might, in the opinion of the attending clinician, put the patient at significant risk if he/she were to participate in the trial
- •Patients with suspected or confirmed active pulmonary tuberculosis or Pneumocystis jirovecii pneumonia (also known as PCP or PJP) are excluded from the CAP comparison, as these infections are caused by specific organisms with distinct pathologies, and so are not usually categorised as CAP. Eligibility for the CAP comparison also requires planned antibiotic treatment, so patients being treated solely for fungal or viral pneumonia are not eligible.
- •Patients with SARS-CoV-2 and influenza co-infection are eligible, but would be excluded from certain comparisons if the attending clinician believes that there is a specific contra-indication to one of the active drug treatment arms (see Protocol Appendix 2, Appendix 3 for children, and Appendix 4 for pregnant and breastfeeding women), or that the patient should definitely be receiving one of the active drug treatment arms then that arm will not be available for randomisation for that patient. For patients who lack capacity, an advanced directive or behaviour that clearly indicates that they would not wish to participate in the trial would be considered sufficient reason to exclude them from the trial.
- •Patients who have been previously recruited into RECOVERY are eligible to be recruited again as long as their previous randomisation was >6 months ago. Patients will not be recruited into the same randomised comparison (e.g. sotrovimab vs. usual care) on more than one occasion, regardless of how far apart they occur.
- •In some locations, children (aged <18 years) will not be recruited, to comply with local and national regulatory approvals (see Appendix 6).
- •Note: the eligibility criteria has changed from COVID-19 to pneumonia (Influenza & CAP). For detailed information about previous eligibility criteria please see the previous Protocol's on the study website: https://www.recoverytrial.net/uk/for-site-staff/site-set-up-1/regulatory-documents
排除标准
- 未提供
研究组 & 干预措施
Lopinavir-Ritonavir
First (main) randomisation part A (COVID-19)
[This arm is now closed to recruitment]
干预措施: Lopinavir-Ritonavir (Drug)
Standard Care
Patient receives usual hospital care
Corticosteroids
First (main) randomisation part A (COVID-19)
[This arm is now closed to recruitment]
干预措施: Corticosteroid (Drug)
Corticosteroids (dexamethasone) (influenza arm)
Randomisation part I (influenza)
干预措施: Corticosteroids (dexamethasone) (Drug)
Corticosteroids (dexamethasone) (community-acquired pneumonia arm)
Randomisation part M (community-acquired pneumonia)
干预措施: Corticosteroids (dexamethasone) (Drug)
Sotrovimab
First (main) randomisation part J (COVID-19)
[This arm is now closed to recruitment]
干预措施: Sotrovimab (Drug)
Molnupiravir
First (main) randomisation part K (COVID-19)
[This arm is now closed to recruitment]
干预措施: Molnupiravir (Drug)
Paxlovid
First (main) randomisation part L (COVID-19)
[This arm is now closed to recruitment]
干预措施: Paxlovid (Drug)
Convalescent plasma
First (main) randomisation part B (COVID-19)
[This arm is now closed to recruitment]
干预措施: Convalescent plasma (Biological)
Intravenous Immunoglobulin
First (main) randomisation part A (children only)
[This arm is now closed to recruitment]
干预措施: Immunoglobulin (Biological)
Synthetic neutralising antibodies
First (main) randomisation part B (COVID-19)
[This arm is now closed to recruitment]
干预措施: Synthetic neutralising antibodies (Drug)
High Dose Corticosteroids
First (main) randomisation part E (COVID-19)
[This arm is now closed to recruitment]
干预措施: High Dose Corticosteroid (Drug)
Anakinra
Randomisation for children only with PIMS-TS
(Children with COVID-19 pneumonia are not eligible for this comparison).
[This arm is now closed to recruitment]
干预措施: Anakinra (Drug)
Hydroxychloroquine
First (main) randomisation part A (COVID-19)
[This arm is now closed to recruitment]
干预措施: Hydroxychloroquine (Drug)
Azithromycin
First (main) randomisation part A (COVID-19)
[This arm is now closed to recruitment]
干预措施: Azithromycin (Drug)
Tocilizumab
Participants with progressive COVID-19 (as evidenced by hypoxia and an inflammatory state) may undergo randomisation between Tocilizumab and no additional treatment.
(Children with COVID-19 pneumonia are not eligible for this comparison).
[This arm is now closed to recruitment]
干预措施: Tocilizumab (Drug)
Aspirin
First (main) randomisation part C (COVID-19)
[This arm is now closed to recruitment]
干预措施: Aspirin (Drug)
Dimethyl fumarate
First (main) randomisation part A (COVID-19) (UK adults only; early phase assessment)
[This arm is now closed to recruitment]
干预措施: Dimethyl fumarate (Drug)
Colchicine
First (main) randomisation part A (COVID-19)
[This arm is now closed to recruitment]
干预措施: Colchicine (Drug)
Baricitinib
First (main) randomisation part D (COVID-19)
[This arm is now closed to recruitment]
干预措施: Baricitinib (Drug)
Empagliflozin
First (main) randomisation part F (COVID-19)
[This arm is now closed to recruitment]
干预措施: Empagliflozin (Drug)
Baloxavir marboxil
Randomisation part G (influenza)
干预措施: Baloxavir Marboxil (Drug)
Oseltamivir
Randomisation part H (influenza)
干预措施: Oseltamivir (Drug)
结局指标
主要结局
All-cause mortality
时间窗: Within 28 days after randomisation
For each pairwise comparison with the 'no additional treatment' arm, the primary objective is to provide reliable estimates of the effect of study treatments on all-cause mortality.
Influenza co-primary outcome: All-cause mortality (with subsidiary analysis of cause of death and death at various timepoints following discharge)
时间窗: Within 28 days after randomisation
Influenza co-primary outcome: Time to discharge alive from hospital
时间窗: Within the first 28-days
Community-acquired pneumonia: All-cause mortality (with subsidiary analyses of cause of death and of death at various timepoints following discharge)
时间窗: Within 28 days after randomisation
For each pairwise comparison with the 'no additional treatment' arm, the primary objective is to provide reliable estimates of the effect of study treatments on all-cause mortality.
次要结局
- COVID-19 & community-acquired pneumonia: Duration of hospital stay(Within 28 days and up to 6 months after the main randomisation)
- COVID-19 & community-acquired pneumonia: Composite endpoint of death or need for mechanical ventilation or ECMO(Within 28 days and up to 6 months after the main randomisation)
- Influenza: Composite endpoint of death or need for mechanical ventilation or ECMO(Within 28 days and up to 6 months after the main randomisation)
- Community-acquired pneumonia: Duration of hospital stay(Within 28 days and up to 6 months after the main randomisation)
- Community-acquired pneumonia: Composite endpoint of death or need for mechanical ventilation or ECMO(Within 28 days and up to 6 months after the main randomisation)