A Phase 3 interventional study of Lopinavir-Ritonavir and Corticosteroid in Pneumonia, sponsored by University of Oxford. Recruiting at 16 sites in 16 countries. Open to participants aged 0 Years and older. Per ClinicalTrials.gov, last updated 2026-04-21.
Sponsored by University of Oxford · Phase 3, Interventional, and Treatment
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)
The RECOVERY trial has already shown that:
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.
ELIGIBILITY AND RANDOMISATION: This protocol (version 28.0) includes treatment comparisons for influenza and community-acquired pneumonia. No COVID-19 comparisons are currently open in the trial. Eligible patients are randomly allocated between one or more treatment arms, each to be given in addition to the usual standard of care in the participating hospital. The study is dynamic, and treatments are added and removed as results and suitable treatments become available, or as new infectious respiratory threats emerge. For patients for whom not all the trial arms are appropriate or at locations where not all are available, randomisation will be between fewer comparisons.
All COVID-19 arms of the protocol (Part A to F, and J to L) have now been discontinued with results reported.
The arms currently open to recruitment are as follows:
Part G (Influenza): UK patients ≥12 years old (≥18 years old in other countries), with or without SARS-CoV-2 co-infection, randomised to baloxavir marboxil vrs no additional treatment.
Part H (Influenza): UK patients any age (≥18 years old in other countries), with or without SARS-CoV-2 co-infection, randomised to oseltamivir vrs no additional treatment.
Part I (Influenza): UK patients any age (≥18 years old in other countries), without suspected or confirmed SARS-CoV-2 infection, and with clinical evidence of hypoxia (i.e. receiving oxygen or with oxygen saturations \<92% on room air), randomised to corticosteroids (dexamethasone) vrs no additional treatment.
Part M (Community-acquired pneumonia with planned antibiotic treatment and without suspected or confirmed SARS-CoV-2, influenza, active pulmonary tuberculosis, or Pneumocystis pneumonia): Patients ≥18 years old randomised to corticosteroids (dexamethasone) vs no additional treatment.
For patients for whom not all the trial arms are appropriate or at locations where not all are available, randomisation will be between fewer arms.
ADAPTIVE DESIGN: The interim trial results will be monitored by an independent Data Monitoring Committee (DMC). The most important task for the DMC will be to assess whether the randomised comparisons in the study have provided evidence on mortality that is strong enough (with a range of uncertainty around the results that is narrow enough) to affect national and global treatment strategies. In such a circumstance, the DMC will inform the Trial Steering Committee who will make the results available to the public and amend the trial arms accordingly. New trial arms can be added as evidence emerges that other candidate therapeutics should be evaluated.
OUTCOMES: The main outcomes will be death, discharge, need for ventilation and need for renal replacement therapy. For the main analyses, follow-up will be censored at 28 days after randomisation. Additional information on longer term outcomes may be collected through review of medical records or linkage to medical databases where available (such as those managed by NHS England and equivalent organisations in the devolved nations).
SIMPLICITY OF PROCEDURES: To facilitate collaboration, even in hospitals that suddenly become overloaded, patient enrolment (via the internet) and all other trial procedures are greatly streamlined. Informed consent is simple and data entry is minimal. Randomisation via the internet is simple and quick, at the end of which the allocated treatment is displayed on the screen and can be printed or downloaded. Key follow-up information is recorded at a single timepoint and may be ascertained by contacting participants in person, by phone or electronically, or by review of medical records and databases.
DATA TO BE RECORDED: At randomisation, information will be collected on the identity of the randomising clinician and of the patient, age, sex, major co-morbidity, pregnancy, illness onset date and severity, and any contraindications to the study treatments. The main outcomes will be death (with date and probable cause), discharge (with date), need for ventilation (with number of days recorded) and need for renal replacement therapy.
Other information to be recorded relevant to safety will include acute kidney or liver injury, cardiac arrhythmia, infection, thrombosis, bleeding, metabolic disturbances, and seizures.
Reminders will be sent if outcome data have not been recorded by 28 days after randomisation. Suspected Serious Adverse Reactions (SSARs) to one of the study medications (eg, Stevens-Johnson syndrome, anaphylaxis, aplastic anaemia) will be collected and unexpected SSARs (SUSARs) will be reported in an expedited fashion. Other adverse events will not be recorded but may be available through linkage to medical databases.
NUMBERS TO BE RANDOMISED: The larger the number randomised the more accurate the results will be, but the numbers that can be randomised will depend critically on the epidemiology of the relevant infections over the next few years. If substantial numbers are hospitalised in the participating centres then it may be possible to randomise several thousand with mild disease and a few thousand with severe disease, but realistic, appropriate sample sizes could not be estimated at the start of the trial.
HETEROGENEITY BETWEEN POPULATIONS: If sufficient numbers are studied, it may be possible to generate reliable evidence in certain patient groups (e.g. those with major comorbidity or who are older). To this end, data from this study may be combined with data from other trials of treatments for viral or bacterial pneumonia.
ADD-ON STUDIES: Particular countries or groups of hospitals, may well want to collaborate in adding further measurements or observations, such as serial blood gases or chemistry, or serial documentation of other aspects of disease status. While well-organised additional research studies of the natural history of the disease or of the effects of the trial treatments could well be valuable (although the lack of placebo control may bias the assessment of subjective side-effects, such as gastrointestinal problems), they are not core requirements.
7,990 studies on the registry are indexed under COVID-19; 466 are open to participants now.
This study's planned enrollment of 70,000 is above the median of 102 across 4,364 interventional studies indexed under COVID-19.
Browse COVID-19 studies →University of Oxford is the lead sponsor of 812 studies on the registry; 119 are open to participants now.
Compared within COVID-19, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Pneumonia. The counts are of registry records indexed under each term, refreshed daily. How we classify →
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:
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:
(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 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
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patient receives usual hospital care
First (main) randomisation part A (COVID-19) \[This arm is now closed to recruitment\]
Drug: Corticosteroid
First (main) randomisation part A (COVID-19) \[This arm is now closed to recruitment\]
Drug: Hydroxychloroquine
First (main) randomisation part A (COVID-19) \[This arm is now closed to recruitment\]
Drug: Lopinavir-Ritonavir
First (main) randomisation part A (COVID-19) \[This arm is now closed to recruitment\]
Drug: Azithromycin
First (main) randomisation part B (COVID-19) \[This arm is now closed to recruitment\]
Biological: Convalescent plasma
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). \[This arm is now closed to recruitment\]
Drug: Tocilizumab
First (main) randomisation part A (children only) \[This arm is now closed to recruitment\]
Biological: Immunoglobulin
First (main) randomisation part B (COVID-19) \[This arm is now closed to recruitment\]
Drug: Synthetic neutralising antibodies
First (main) randomisation part C (COVID-19) \[This arm is now closed to recruitment\]
Drug: Aspirin
First (main) randomisation part A (COVID-19) \[This arm is now closed to recruitment\]
Drug: Colchicine
First (main) randomisation part D (COVID-19) \[This arm is now closed to recruitment\]
Drug: Baricitinib
Randomisation for children only with PIMS-TS (Children with COVID-19 pneumonia are not eligible for this comparison). \[This arm is now closed to recruitment\]
Drug: Anakinra
First (main) randomisation part A (COVID-19) (UK adults only; early phase assessment) \[This arm is now closed to recruitment\]
Drug: Dimethyl fumarate
First (main) randomisation part E (COVID-19) \[This arm is now closed to recruitment\]
Drug: High Dose Corticosteroid
First (main) randomisation part F (COVID-19) \[This arm is now closed to recruitment\]
Drug: Empagliflozin
First (main) randomisation part J (COVID-19) \[This arm is now closed to recruitment\]
Drug: Sotrovimab
First (main) randomisation part K (COVID-19) \[This arm is now closed to recruitment\]
Drug: Molnupiravir
First (main) randomisation part L (COVID-19) \[This arm is now closed to recruitment\]
Drug: Paxlovid
Randomisation part G (influenza)
Drug: Baloxavir Marboxil
Randomisation part H (influenza)
Drug: Oseltamivir
Randomisation part I (influenza)
Drug: Corticosteroids (dexamethasone)
Randomisation part M (community-acquired pneumonia)
Drug: Corticosteroids (dexamethasone)
Lopinavir 400mg-Ritonavir 100mg by mouth (or nasogastric tube) every 12 hours for 10 days.
Corticosteroid in the form of dexamethasone administered as an oral (liquid or tablets) or intravenous preparation 6 mg once daily for 10 days. In pregnancy or breastfeeding women, prednisolone 40 mg administered by mouth (or intravenous hydrocortisone 80 mg twice daily) should be used instead of dexamethasone. Corticosteroid (in children ≤44 weeks gestational age, or \>44 weeks gestational age with PIMS-TS only) in the form of Hydrocortisone or Methylprednisolone sodium succinate (see Protocol for timing and dosage)
Hydroxychloroquine by mouth for a total of 10 days (see Protocol for timing and dosage).
Azithromycin 500mg by mouth (or nasogastric tube) or intravenously once daily for 10 days.
Single unit of ABO compatible convalescent plasma (275mls +/- 75 mls) intravenous per day on study days 1 (as soon as possible after randomisation) and 2 (with a minimum of 12 hour interval between 1st and 2nd units).
Tocilizumab by intravenous infusion with the dose determined by body weight (see Protocol for dosage)
Intravenous immunoglobulin (IVIg) for children \>44 weeks gestational age and \<18 years with PIMS-TS only (see Protocol for dosage)
Patients ≥12 years only with COVID-19 pneumonia: A single dose of REGN10933 + REGN10987 8 g (4 g of each monoclonal antibody) in 250ml 0.9% saline infused intravenously over 60 minutes +/- 15 minutes as soon as possible after randomisation
Also known as: REGEN-COV, casirivimab and imdevimab
150 mg by mouth (or nasogastric tube) or per rectum once daily until discharge, for adults ≥18 years old.
1 mg after randomisation followed by 500mcg 12 hours later and then 500 mcg twice daily by mouth or nasogastric tube for 10 days in total, for men ≥18 years old and women ≥55 years old only
UK \[age ≥2 years with COVID pneumonia\] and India \[age ≥18 years with COVID-19 pneumonia\]: 4 mg once daily by mouth or nasogastric tube for 10 days in total.
For children ≥1 \<18 years old only: subcutaneously or intravenously once daily for 7 days or discharge (if sooner). NB Anakinra will be excluded from the randomisation of children \<10 kg in weight.
Early phase assessment. UK adults ≥18 years old only (excluding those on ECMO). 120 mg every 12 hours for 4 doses followed by 240 mg every 12 hours by mouth for 8 days (10 days in total).
Adults ≥18 years old with hypoxia only. Dexamethasone 20 mg (base) once daily by mouth, nasogastric tube or intravenous infusion for 5 days follow by dexamethasone 10 mg (base) once daily by mouth, nasogastric tube or intravenous infusion for 5 days.
Adults ≥18 years old only. 10 mg once daily by mouth for 28 days (or until discharge, if earlier).
UK patients ≥12 years old. 1000 mg in 100 mL 0.9% sodium chloride or 5% dextrose by intravenous infusion over 1 hour as soon as possible after randomisation.
Patients ≥18 years old. 800 mg twice daily for 5 days by mouth.
UK patients ≥18 years old. 300/100 mg twice daily for 5 days by mouth.
Also known as: nirmatrelvir/ritonavir
Patients ≥12 years old in the UK (or ≥18 years old in other countries), with or without SARS-CoV-2 co-infection. 40mg (or 80mg if weight ≥80kg) once daily by mouth or nasogastic tube to be given on day 1 and day 4.
Also known as: Xofluza
Any age in the UK (or ≥18 years old in other countries), with or without SARS-CoV-2 co-infection. 75mg twice daily by mouth or nasogastric tube for five days. (See Protocol for detailed dosage information)
Also known as: Tamiflu
Any age in the UK (or ≥18 years old in other countries), without suspected or confirmed SARS-CoV-2 infection, and with clinical evidence of hypoxia (i.e. receiving oxygen or with oxygen saturations \<92% on room air) 6mg once daily given orally or intravenously for ten days or until discharge (whichever happens earliest)
Patients ≥18 years old with a diagnosis of community-acquired pneumonia (with planned antibiotic use and without suspected or confirmed SARS-CoV-2, influenza, active pulmonary tuberculosis, or Pneumocystis jirovecii infection) 6mg once daily given orally or intravenously for ten days or until discharge (whichever happens earliest)
Community-acquired pneumonia: All-cause mortality (with subsidiary analyses of cause of death and of death at various timepoints following discharge)
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.
Time frame: Within 28 days after randomisation
Influenza co-primary outcome: All-cause mortality (with subsidiary analysis of cause of death and death at various timepoints following discharge)
Time frame: Within 28 days after randomisation
Influenza co-primary outcome: Time to discharge alive from hospital
Time frame: Within the first 28-days
Community-acquired pneumonia: Duration of hospital stay
To assess the effects of study treatment on number of days stay in hospital
Time frame: 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
Among patients not on invasive mechanical ventilation at baseline, the number of patients with a composite endpoint of death or need for invasive mechanical ventilation or ECMO.
Time frame: Within 28 days and up to 6 months after the main randomisation
Influenza: Composite endpoint of death or need for mechanical ventilation or ECMO
Among patients not on invasive mechanical ventilation at baseline, the number of patients with a composite endpoint of death or need for invasive mechanical ventilation or ECMO.
Time frame: Within 28 days and up to 6 months after the main randomisation
Need for (and duration of) ventilation
To assess the effects of study treatment on number of patients who needed any ventilation and (for invasive mechanical ventilation) the number of days it was required
Time frame: Within 28 days and up to 6 months after the main randomisation
Need for renal replacement
To assess the effects of study treatment on number of patients who needed renal replacement therapy
Time frame: Within 28 days and up to 6 months after the main randomisation
Number of patients who had thrombotic events
To assess the effects of study treatment on number of patients who had thrombotic events, defined as either (i) acute pulmonary embolism; (ii) deep vein thrombosis; (iii) ischaemic stroke; (iv) myocardial infarction; or (v) systemic arterial embolism.
Time frame: Within 28 days and up to 6 months after the main randomisation
Not enrolling at this site.
Plan to share: Yes — RECOVERY data are available via the Infectious Diseases Data Observatory (IDDO), or by contacting the study team (for datasets not held by IDDO). https://www.iddo.org/covid19/data-reuse/accessing-data https://www.ndph.ox.ac.uk/data-access
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: Datasets are available.
Access criteria: RECOVERY data are available via the Infectious Diseases Data Observatory (IDDO), or by contacting the study team (for datasets not held by IDDO).
Data sharing details ↗ · www.iddo.org
Started Mar 2020 (actual). Primary completion is estimated for Sep 2028, 102 months after the start.
Of 285 non-industry phase 3 interventional studies under COVID-19, half reached primary completion within 10 months of starting (the median), counting those still running; a quarter within 5 and three quarters within 19. This study's planned 102 months is above that.
Counting every sponsor, half of 453 studies reached it within 9 months; a quarter within 4 and three quarters within 17.
How these figures are worked out, and which studies are left out of them.
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Studies of the drugs tested here: Hydroxychloroquine · Azithromycin · Tocilizumab · Immunoglobulins · Aspirin · Colchicine · Baricitinib · Interleukin 1 Receptor Antagonist Protein · Dimethyl Fumarate · Empagliflozin · Sotrovimab · Molnupiravir · Baloxavir · Oseltamivir · Dexamethasone