THC Science

The Randomised Evaluation of COVID-19 Therapy (RECOVERY Trial)^[1] is a large-enrollment clinical trial of possible treatments for people in the United Kingdom admitted to hospital with severe COVID-19 infection.^[2]^[3]^[4] The trial was later expanded to Indonesia, Nepal and Vietnam.^[5] The trial has tested ten interventions on adults: eight repurposed drugs, one newly developed drug and convalescent plasma.^[2]

Treatments

As of 20 March 2021, the following treatments are allocated at random to hospitalized people with severe COVID-19 infection:^[2]^[6]

REGN-COV2 (a cocktail of two anti-viral monoclonal antibodies)
Baricitinib (an immunomodulatory drug used in rheumatoid arthritis)
Dimethyl fumarate (adults only, early phase assessment)
Infliximab (adults only)
High-dose dexamethasone (adults with hypoxia only)

Children with PIMS-TS may also be allocated the following:^[6]

Low-dose dexamethasone (a steroid, which reduces inflammation)
Intravenous immunoglobulin
Tocilizumab (an anti-inflammatory)
Anakinra (a drug used to treat rheumatoid arthritis)

The following treatments have previously been included in the trial:

Lopinavir-Ritonavir (an HIV medication)
Hydroxychloroquine (used to treat malaria and rheumatism)
Azithromycin (an antibiotic)
Convalescent plasma (blood plasma from people who have recovered from COVID-19 and which may contain antibodies against the SARS-CoV-2 virus)

The latter four arms were closed to new entrants after being shown to be ineffective.^[7]^[8]^[9]^[10]

Dexamethasone and Tocilizumab were closed to new adult entries after positive results.

Design

The RECOVERY Trial is a large-scale, randomized controlled trial.^[2]^[11] The primary objective of the trial is to "provide reliable estimates of the effect of study treatments on all-cause mortality at 28 days after first randomisation".^[2]^[11]

It is an "open label" study: people receiving the treatment and the attending clinicians both know which treatment is being administered.^[2] It is a multi-arm adaptive clinical trial, meaning that new treatments can be added into the trial as it progresses, and other treatment "arms" closed to new enrolment when results have been produced.^[4]

The trial protocol was developed in March 2020. The design minimizes the administrative load on hospital staff, who at the time were facing the prospect of overwhelming numbers of COVID-19 admissions.^[12]^[13]

When people who have been hospitalised with COVID-19 are enrolled in the trial, they are automatically randomized to receive trial treatments. If any treatment is contra-indicated (or positively indicated) for that patient, or is not available, then that treatment is not included in the randomization process. The main randomization stage has three parts, so that patients might be allocated none, one, two or three of the trial treatments. If their disease progresses, there may also be a second randomization.^[13]

The very fast setting up of the trial was crucial for the fast-developing COVID-19 pandemic. Martin Landray, one of the trial's creators, said in March 2021 "I think it has set a new standard for what can be delivered and not just for pandemics. It would be a travesty if we went back to a situation where it takes years sometimes to get a trial off the ground."^[14]

Operations

The trial is run by the Nuffield Departments of Population Health and of Medicine at the University of Oxford.^[8]^[12] The study is led by Peter Horby and Martin Landray who serve as Co-Chief Investigators of the trial.^[15]^[16] By July 2020, the trial was in progress at 176 NHS hospitals in the UK, involving many thousands of health professionals.^[17]

The trial began in March 2020. As of March 2021 the trial had enrolled more than 40,000 COVID-19 participants admitted to hospitals in the UK;^[14] the estimated primary completion date was December 2021, and the estimated study completion date was December 2031.^[11]^[9]

Results

Dexamethasone

On 22 June 2020, preliminary results were published in a preprint showing that low-dose dexamethasone treatment reduced the death rate by one third in hospitalized people needing ventilators due to severe COVID-19 infection, and by one fifth in people treated with oxygen therapy. There was no benefit (and the possibility of harm) among people who did not require oxygen.^[18] The preliminary report was subsequently published in The New England Journal of Medicine.^[19]

Impacts

Six days before the pre-print, these results had been announced in a news release.^[20] A UK Therapeutic Alert was issued the same day, and all the Chief Medical Officers in the United Kingdom exceptionally recommended an immediate change of UK-wide clinical practice, in advance of publication of any final paper.^[21]

Demand for dexamethasone surged after publication of the preprint.^[22]

Based on the preliminary, unpublished results of the RECOVERY trial, the US National Institutes of Health COVID-19 Treatment Guidelines Panel recommended dexamethasone in patients with COVID-19 who are on mechanical ventilation or those who require supplemental oxygen, and recommended against dexamethasone for those not requiring supplemental oxygen.^[23]

Other countries granted specific approval for the drug as part of standard medical care, among them Japan,^[24] Taiwan^[25] and South Africa.^[26]

A pre-print study, which was awarded Health Data Research UK Open Access Publication of the Month for August 2020, found that the discovery would save approximately 650,000 lives globally over the course of six months.^[27]^[28]

Limitations of dexamethasone result

John Fletcher, research editor at the BMJ, noted that there were "limitations and causes of concern" in the dexamethasone results.^[22]
Around a third of patients in the trial were still in hospital at the end of the 28-day trial period, so their final outcomes were not known.^[22]
As an immunosuppressive drug, there are fears that dexamethasone could make the illness worse, and prolong the infection in patients where the immune system has not yet overreacted and caused inflammation.^[12]^[29]
The preprint authors themselves warned that "the results are consistent with possible harm" in patients who did not require oxygen at the time of enrolment.^[18] The trial observed a 22% increase in mortality in these patients (rate ratio 1.22 [95% Confidence Interval 0.93 to 1.61]; p=0.14), though this observation may still be due to chance.^[18]
Responding to the publication, the WHO emphasized that dexamethasone should only be used for patients with severe or critical disease, under close clinical supervision, stating that "There is no evidence this drug works for patients with mild disease or as a preventative measure, and it could cause harm."^[30]

Confirmation of dexamethasone result

The results of this initial finding have now been replicated in a systematic review by the World Health Organization's Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group.^[31]

Hydroxychloroquine

On 5 June 2020, the trial determined that there was no clinical benefit from use of hydroxychloroquine in people hospitalized with COVID-19.^[8]

Lopinavir-ritonavir

On 29 June 2020, chief investigators of the trial reported there was no clinical benefit from use of lopinavir-ritonavir in 1,596 people hospitalized with severe COVID-19 infection over 28 days of treatment.^[7] These results were published in The Lancet on 5 October 2020.^[32]

Azithromycin

In a news release on 14 December 2020, the chief investigators announced that they had found no benefit from azithromycin in patients hospitalised with COVID-19. 2582 patients had received azithromycin, and 5182 were randomised to usual care alone. 28-day mortality in both cohorts was 19%.^[9] These preliminary results were released as a preprint on the same day.^[33]

Convalescent plasma

In a news release on 15 January 2021, the chief investigators announced the closure of the convalescent plasma arm of the trial. Among 1873 reported deaths from 10,405 patients, the trial reported "no significant difference in the primary endpoint of 28-day mortality (18% convalescent plasma vs. 18% usual care alone; risk ratio 1.04 [95% confidence interval 0.95-1.14]; p=0.34)".^[10] The article with full results was published on 14 May 2021.^[34]

Tocilizumab

Tocilizumab significantly reduces the risk of death when given to hospitalised patients with severe COVID-19. 2022 patients allocated to Tocilizumab were compared to 2094 who received standard hospital care. "596 (29%) of the patients in the tocilizumab group died within 28 days compared with 694 (33%) patients in the usual care group (rate ratio 0·86; [95% confidence interval [CI] 0·77 to 0·96]; p=0·007), an absolute difference of 4%." Receiving tocilizumab also increased the chance of discharge from hospital within 28 days.^[35]^[36]^[37]

This result supports the earlier findings of the Remap-Cap trial on the effectiveness of Tocilizumab for patients in intensive care, and extends those findings to a wider group of patients.^[38]

References

^ "ISRCTN - ISRCTN50189673: A randomised trial of treatments to prevent death in patients hospitalised with COVID-19 (coronavirus)". www.isrctn.com.
^ ^a ^b ^c ^d ^e ^f "RECOVERY Trial". Retrieved 17 June 2020.
^ "Coronavirus: Dexamethasone being used to treat NHS patients today". BBC News. 17 June 2020. Retrieved 17 June 2020.
^ ^a ^b "Biggest COVID-19 trial tests repurposed drugs first". Nature Biotechnology. 38 (5): 510. 11 May 2020. doi:10.1038/s41587-020-0528-x. PMID 32393915. S2CID 218593584. Retrieved 26 June 2020.
^ "International sites — RECOVERY Trial". www.recoverytrial.net. Retrieved 2021-05-17.
^ ^a ^b "Recovery Trial Protocol v15" (PDF). Recovery Trial. Retrieved 4 Feb 2021.{{cite web}}: CS1 maint: url-status (link)
^ ^a ^b "No clinical benefit from use of lopinavir-ritonavir in hospitalised COVID-19 patients studied in RECOVERY" (PDF). RECOVERY Trial: Statement from the Chief Investigators. 29 June 2020. Retrieved 30 June 2020.
^ ^a ^b ^c "No clinical benefit from use of hydroxychloroquine in hospitalised patients with COVID-19". Recovery Trial, Nuffield Department of Population Health, University of Oxford, UK. 2020-06-05. Retrieved 2020-06-07.
^ ^a ^b ^c Peter Horby; Martin Landray (14 December 2020). "RECOVERY trial finds no benefit from azithromycin in patients hospitalised with COVID-19". RECOVERY Trial.
^ ^a ^b RECOVERY trial chief investigators (15 January 2021). "Recovery trial closes recruitment for convalescent plasma treatment for patients hospitalised with COVID-19". Retrieved 15 January 2021.{{cite web}}: CS1 maint: url-status (link)
^ ^a ^b ^c Clinical trial number NCT04381936 for "Randomised Evaluation of COVID-19 Therapy (RECOVERY)" at ClinicalTrials.gov. 2 March 2021; page is updated from time to time.
^ ^a ^b ^c Fergus Walsh (20 June 2020). "At last some good news about coronavirus". BBC News. Retrieved 20 June 2020.
^ ^a ^b "Randomised evaluation of COVID-19 therapy (RECOVERY) - Trial protocol v11" (PDF). RECOVERY Trial. 21 Nov 2020. Retrieved 14 Dec 2020.
^ ^a ^b Gallagher, James (25 March 2021). "Covid: The London bus trip that saved maybe a million lives". BBC News.
^ "Preliminary trial results find dexamethasone reduces death in hospitalised patients with severe respiratory complications of COVID-19 - UK Research and Innovation". www.ukri.org. UK Research and Innovation. Retrieved 19 October 2020.
^ editor, Sarah Boseley Health (17 June 2020). "Dexamethasone: low-cost drug helps prevent deaths of sickest coronavirus patients". The Guardian. {{cite news}}: |last1= has generic name (help)
^ KupferschmidtJul. 2, Kai (2 July 2020). "One U.K. trial is transforming COVID-19 treatment. Why haven't others delivered more results?". Science. Retrieved 19 October 2020.{{cite news}}: CS1 maint: numeric names: authors list (link)
^ ^a ^b ^c ^d ^e RECOVERY Collaborative Group (2020). "Effect of Dexamethasone in Hospitalized Patients with COVID-19 – Preliminary Report". MedRXiv: 2020.06.22.20137273. doi:10.1101/2020.06.22.20137273. S2CID 219965377. Retrieved 23 June 2020.
^ Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, et al. (July 2020). "Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report". New England Journal of Medicine. 384 (8): 693–704. doi:10.1056/NEJMoa2021436. PMC 7383595. PMID 32678530.
^ "Dexamethasone reduces death in hospitalised patients with severe respiratory complications of COVID-19". University of Oxford. 16 June 2020. Retrieved 16 June 2020.
^ "Dexamethasone in COVID-19" (PDF). 16 June 2020. Retrieved 23 June 2020.
^ ^a ^b ^c Mahase E (June 2020). "Covid-19: Demand for dexamethasone surges as RECOVERY trial publishes preprint". BMJ. 369: m2512. doi:10.1136/bmj.m2512. PMID 32576548.
^ "The National Institutes of Health COVID-19 Treatment Guidelines Panel Provides Recommendations for Dexamethasone in Patients with COVID-19". NIH COVID-19 Treatment Guidelines. National Institutes of Health. 25 June 2020. Retrieved 26 June 2020.
^ hermesauto (2020-07-22). "Japan approves dexamethasone as coronavirus treatment". The Straits Times. Retrieved 2020-09-06.
^ "Taiwan provisionally approves dexamethasone as coronavirus treatment". Reuters. 2020-08-04. Retrieved 2020-09-06.
^ "South Africa approves dexamethasone to treat COVID-19".
^ "The potential health and economic impact of dexamethasone treatment for patients with COVID-19". HDR UK. Retrieved 2020-09-06.
^ Aguas, Ricardo; Mahdi, Adam; Shretta, Rima; Horby, Peter; Landray, Martin; White, Lisa J. (2020-07-30). "The potential health and economic impact of dexamethasone treatment for patients with COVID-19". MedRxiv: 2020.07.29.20164269. doi:10.1101/2020.07.29.20164269. S2CID 220846974.
^ Roni Caryn Rabin (24 June 2020). "Breakthrough Drug for Covid-19 May Be Risky for Mild Cases". New York Times. Retrieved 25 June 2020.
^ "WHO Director-General's opening remarks at the media briefing on COVID-19 - 22 June 2020". World Health Organization. Retrieved 25 June 2020.
^ Group, The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working; Sterne, Jonathan A. C.; Murthy, Srinivas; Diaz, Janet V.; Slutsky, Arthur S.; Villar, Jesús; Angus, Derek C.; Annane, Djillali; Azevedo, Luciano Cesar Pontes; Berwanger, Otavio; Cavalcanti, Alexandre B. (2020-09-02). "Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis". JAMA. 324 (13): 1330–1341. doi:10.1001/jama.2020.17023. PMC 7489434. PMID 32876694.{{cite journal}}: CS1 maint: numeric names: authors list (link)
^ Horby, Peter W.; Mafham, Marion; Bell, Jennifer L.; Linsell, Louise; Staplin, Natalie; Emberson, Jonathan; Palfreeman, Adrian; Raw, Jason; Elmahi, Einas; Prudon, Benjamin; Green, Christopher; Carley, Simon; Chadwick, David; Davies, Matthew; Wise, Matthew P.; Baillie, J Kenneth; Chappell, Lucy C.; Faust, Saul N.; Jaki, Thomas; Jefferey, Katie; Lim, Wei Shen; Montgomery, Alan; Rowan, Kathryn; Juszczak, Edmund; Haynes, Richard; Landray, Martin J. (5 October 2020). "Lopinavir–ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial". The Lancet. 396 (10259): 1345–1352. doi:10.1016/S0140-6736(20)32013-4. PMC 7535623. PMID 33031764.
^ Horby, Peter W.; et al. (14 December 2020). "Azithromycin in Hospitalised Patients with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial". MedRxiv: 2020.12.10.20245944. doi:10.1101/2020.12.10.20245944. Retrieved 14 December 2020.
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BrownCarolineCWrightCatherineCWrightDemiDWrightFrancescaFWrightImogenIWrightLeeLWrightLianneLWrightPetePWrightRachelRWrightRebeccaRWrightStephanieSWrightTimTWroeCarolineCWroeHannahHWuHenryHWuPeishanPWuPenseePWubetuJonathanJWulandariRetnoRWyattCraigCWyn-GriffithsFrederickFWynterInezIXavierBindhuBXhikolaArnoldAXiaZhongyangZXiaoHuiyuanHYakubiMassehMYanMayMYangFredaFYangYingjiaYYanneyMichaelMYapWoei LinWLYaqoobNabilNYaqubNaairahNYasminSalimaSYatesBryanBYatesDavidDYatesEdwardEYatesHelenHYatesJulieJYatesMarkMYearwood MartinCharlotteCYeatmanAndrewAYeinKhinKYelnoorkarFionaFYewPeterPYipKawaiKYlquimicheLauraLYlquimiche MellyLauraLYnterInezIYongHHYorkeJemmaJYouensJasmineJYounes IbrahimAbdelAYoungEoinEYoungGailGYoungLouiseLYoungRichardRYousafzarAsfandAYoussoufSajedaSYousufAhmedAYuChrissieCYungBernardBYusefDanielDYusefSaidSYusufIntekhabIZafarAnna-SophiaASZagaloSilviaSZaherSuSZahoorAqsaAZakiKareemKZakirNabhanNZalewskaKasiaKZamalloaAneAZamanMohsinMZamanRaisaRZamanShakirSZamikulaJulieJZammitLouiseLZammit-MangionMarieMZarbLynnLZebrackiEstherEZehnderDanielDZeidanLisaLZelmanMarianMZhaoXiaobeiXZhengDonglingDZhuDoreenDZiaMadihaMZibdehOmarOZill-E-HumaRabiaRZinEi ThanktETZindondaVeronicaVZinkinEleanorEZinyembaVivianVZipitisChristosCZmierczakArkadiuszAZubirAzamAZuhaRoslinRZuhraNazNZulaikhaRashaRZulfikarSabrinaSZulloCarolCZuriaga-AlvaroAnaAZuurbierWillWZyengiShebaS (2021-05-14). 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External links

[1] "ISRCTN - ISRCTN50189673: A randomised trial of treatments to prevent death in patients hospitalised with COVID-19 (coronavirus)". www.isrctn.com.

[RECOVERY_Home-2] ^ ^a ^b ^c ^d ^e ^f "RECOVERY Trial". Retrieved 17 June 2020.

[BBC17June20-3] "Coronavirus: Dexamethasone being used to treat NHS patients today". BBC News. 17 June 2020. Retrieved 17 June 2020.

[NatBio_11May20-4] "Biggest COVID-19 trial tests repurposed drugs first". Nature Biotechnology. 38 (5): 510. 11 May 2020. doi:10.1038/s41587-020-0528-x. PMID 32393915. S2CID 218593584. Retrieved 26 June 2020.

[5] "International sites — RECOVERY Trial". www.recoverytrial.net. Retrieved 2021-05-17.

[Recovery_Protocol-6] "Recovery Trial Protocol v15" (PDF). Recovery Trial. Retrieved 4 Feb 2021.{{cite web}}: CS1 maint: url-status (link)

[lop-rit-7] "No clinical benefit from use of lopinavir-ritonavir in hospitalised COVID-19 patients studied in RECOVERY" (PDF). RECOVERY Trial: Statement from the Chief Investigators. 29 June 2020. Retrieved 30 June 2020.

[rec-nobenefit-8] "No clinical benefit from use of hydroxychloroquine in hospitalised patients with COVID-19". Recovery Trial, Nuffield Department of Population Health, University of Oxford, UK. 2020-06-05. Retrieved 2020-06-07.

[Azithromycin-20201214-9] Peter Horby; Martin Landray (14 December 2020). "RECOVERY trial finds no benefit from azithromycin in patients hospitalised with COVID-19". RECOVERY Trial.

[Plasma-20210115-10] RECOVERY trial chief investigators (15 January 2021). "Recovery trial closes recruitment for convalescent plasma treatment for patients hospitalised with COVID-19". Retrieved 15 January 2021.{{cite web}}: CS1 maint: url-status (link)

[rec-04381936-11] Clinical trial number NCT04381936 for "Randomised Evaluation of COVID-19 Therapy (RECOVERY)" at ClinicalTrials.gov. 2 March 2021; page is updated from time to time.

[BBC_20Jun20-12] Fergus Walsh (20 June 2020). "At last some good news about coronavirus". BBC News. Retrieved 20 June 2020.

[Protocol-13] "Randomised evaluation of COVID-19 therapy (RECOVERY) - Trial protocol v11" (PDF). RECOVERY Trial. 21 Nov 2020. Retrieved 14 Dec 2020.

[gallagher-14] Gallagher, James (25 March 2021). "Covid: The London bus trip that saved maybe a million lives". BBC News.

[15] "Preliminary trial results find dexamethasone reduces death in hospitalised patients with severe respiratory complications of COVID-19 - UK Research and Innovation". www.ukri.org. UK Research and Innovation. Retrieved 19 October 2020.

[16] tor, Sarah Boseley Health (17 June 2020). "Dexamethasone: low-cost drug helps prevent deaths of sickest coronavirus patients". The Guardian. {{cite news}}: |last1= has generic name (help)

[17] KupferschmidtJul. 2, Kai (2 July 2020). "One U.K. trial is transforming COVID-19 treatment. Why haven't others delivered more results?". Science. Retrieved 19 October 2020.{{cite news}}: CS1 maint: numeric names: authors list (link)

[Paper_22June2020-18] RECOVERY Collaborative Group (2020). "Effect of Dexamethasone in Hospitalized Patients with COVID-19 – Preliminary Report". MedRXiv: 2020.06.22.20137273. doi:10.1101/2020.06.22.20137273. S2CID 219965377. Retrieved 23 June 2020.

[NEJM-17July20-19] Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, et al. (July 2020). "Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report". New England Journal of Medicine. 384 (8): 693–704. doi:10.1056/NEJMoa2021436. PMC 7383595. PMID 32678530.

[Oxford_16Jun2020-20] "Dexamethasone reduces death in hospitalised patients with severe respiratory complications of COVID-19". University of Oxford. 16 June 2020. Retrieved 16 June 2020.

[CMO_16June2020-21] "Dexamethasone in COVID-19" (PDF). 16 June 2020. Retrieved 23 June 2020.

[BMJ_23Jun20-22] Mahase E (June 2020). "Covid-19: Demand for dexamethasone surges as RECOVERY trial publishes preprint". BMJ. 369: m2512. doi:10.1136/bmj.m2512. PMID 32576548.

[23] "The National Institutes of Health COVID-19 Treatment Guidelines Panel Provides Recommendations for Dexamethasone in Patients with COVID-19". NIH COVID-19 Treatment Guidelines. National Institutes of Health. 25 June 2020. Retrieved 26 June 2020.

[24] rmesauto (2020-07-22). "Japan approves dexamethasone as coronavirus treatment". The Straits Times. Retrieved 2020-09-06.

[25] "Taiwan provisionally approves dexamethasone as coronavirus treatment". Reuters. 2020-08-04. Retrieved 2020-09-06.

[26] "South Africa approves dexamethasone to treat COVID-19".

[27] "The potential health and economic impact of dexamethasone treatment for patients with COVID-19". HDR UK. Retrieved 2020-09-06.

[28] Aguas, Ricardo; Mahdi, Adam; Shretta, Rima; Horby, Peter; Landray, Martin; White, Lisa J. (2020-07-30). "The potential health and economic impact of dexamethasone treatment for patients with COVID-19". MedRxiv: 2020.07.29.20164269. doi:10.1101/2020.07.29.20164269. S2CID 220846974.

[NYT_24Jun20-29] Roni Caryn Rabin (24 June 2020). "Breakthrough Drug for Covid-19 May Be Risky for Mild Cases". New York Times. Retrieved 25 June 2020.

[WHO_22Jun20-30] "WHO Director-General's opening remarks at the media briefing on COVID-19 - 22 June 2020". World Health Organization. Retrieved 25 June 2020.

[31] Group, The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working; Sterne, Jonathan A. C.; Murthy, Srinivas; Diaz, Janet V.; Slutsky, Arthur S.; Villar, Jesús; Angus, Derek C.; Annane, Djillali; Azevedo, Luciano Cesar Pontes; Berwanger, Otavio; Cavalcanti, Alexandre B. (2020-09-02). "Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis". JAMA. 324 (13): 1330–1341. doi:10.1001/jama.2020.17023. PMC 7489434. PMID 32876694.{{cite journal}}: CS1 maint: numeric names: authors list (link)

[Lancet-20201005-32] Horby, Peter W.; Mafham, Marion; Bell, Jennifer L.; Linsell, Louise; Staplin, Natalie; Emberson, Jonathan; Palfreeman, Adrian; Raw, Jason; Elmahi, Einas; Prudon, Benjamin; Green, Christopher; Carley, Simon; Chadwick, David; Davies, Matthew; Wise, Matthew P.; Baillie, J Kenneth; Chappell, Lucy C.; Faust, Saul N.; Jaki, Thomas; Jefferey, Katie; Lim, Wei Shen; Montgomery, Alan; Rowan, Kathryn; Juszczak, Edmund; Haynes, Richard; Landray, Martin J. (5 October 2020). "Lopinavir–ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial". The Lancet. 396 (10259): 1345–1352. doi:10.1016/S0140-6736(20)32013-4. PMC 7535623. PMID 33031764.

[medRxiv-20201214-33] Horby, Peter W.; et al. (14 December 2020). "Azithromycin in Hospitalised Patients with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial". MedRxiv: 2020.12.10.20245944. doi:10.1101/2020.12.10.20245944. Retrieved 14 December 2020.

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IbrahimAbdelAYoungEoinEYoungGailGYoungLouiseLYoungRichardRYousafzarAsfandAYoussoufSajedaSYousufAhmedAYuChrissieCYungBernardBYusefDanielDYusefSaidSYusufIntekhabIZafarAnna-SophiaASZagaloSilviaSZaherSuSZahoorAqsaAZakiKareemKZakirNabhanNZalewskaKasiaKZamalloaAneAZamanMohsinMZamanRaisaRZamanShakirSZamikulaJulieJZammitLouiseLZammit-MangionMarieMZarbLynnLZebrackiEstherEZehnderDanielDZeidanLisaLZelmanMarianMZhaoXiaobeiXZhengDonglingDZhuDoreenDZiaMadihaMZibdehOmarOZill-E-HumaRabiaRZinEi ThanktETZindondaVeronicaVZinkinEleanorEZinyembaVivianVZipitisChristosCZmierczakArkadiuszAZubirAzamAZuhaRoslinRZuhraNazNZulaikhaRashaRZulfikarSabrinaSZulloCarolCZuriaga-AlvaroAnaAZuurbierWillWZyengiShebaS (2021-05-14). "Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial (RECOVERY Collaborative Group)". The Lancet: S0140673621008977. doi:10.1016/S0140-6736(21)00897-7. PMC 8121538. PMID 34000257.

[Tocilizumab-20210211-35] "Tocilizumab reduces deaths in patients hospitalised with COVID-19". Recovery Trial. 11 February 2021. Retrieved 11 February 2021.

[BBC-20210211-36] Michelle Roberts (11 February 2021). "Arthritis drug tocilizumab cuts deaths from Covid". BBC News Online. BBC. Retrieved 11 February 2021.

[pmid33933194-37] Gupta S, Leaf DE (May 2021). "Tocilizumab in COVID-19: some clarity amid controversy". Lancet. 397 (10285): 1599–1601. doi:10.1016/S0140-6736(21)00712-1. PMC 8084409. PMID 33933194.

[Guardian-20210211-38] Nicola Davis (11 February 2021). "Arthritis drug that helps Covid ICU patients has wider benefits, trial finds". Guardian News. The Guardian. Retrieved 11 February 2021.

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@@ Line 3: / Line 3: @@
 [[File:Recovery-logo-chosen-mar-2020.jpg|right]]
 {{COVID-19 pandemic sidebar}}
-The '''Randomised Evaluation of COVID-19 Therapy''' ('''RECOVERY Trial''')<ref>{{Cite web|url=http://www.isrctn.com/ISRCTN50189673|title=ISRCTN - ISRCTN50189673: A randomised trial of treatments to prevent death in patients hospitalised with COVID-19 (coronavirus)|website=www.isrctn.com}}</ref> is a large-enrollment [[clinical trial]] of possible treatments for people in the [[United Kingdom]] admitted to hospital with severe [[COVID-19]] infection.<ref name="RECOVERY Home">{{cite web |title=RECOVERY Trial |url=https://www.recoverytrial.net/ |access-date=17 June 2020}}</ref><ref name="BBC17June20">{{cite web |title=Coronavirus: Dexamethasone being used to treat NHS patients today |url=https://www.bbc.co.uk/news/health-53077893 |access-date=17 June 2020}}</ref><ref name="NatBio 11May20" /> The trial was later expanded to [[Indonesia]], [[Nepal]] and [[Vietnam]].<ref>{{Cite web|title=International sites — RECOVERY Trial|url=https://www.recoverytrial.net/international|access-date=2021-05-17|website=www.recoverytrial.net}}</ref> The trial has tested ten interventions on adults: eight [[COVID-19 drug repurposing research|repurposed drugs]], one [[COVID-19 drug development|newly developed drug]] and [[antiserum|convalescent plasma]].<ref name="RECOVERY Home" />
+The '''Randomised Evaluation of COVID-19 Therapy''' ('''RECOVERY Trial''')<ref>{{Cite web|url=http://www.isrctn.com/ISRCTN50189673|title=ISRCTN - ISRCTN50189673: A randomised trial of treatments to prevent death in patients hospitalised with COVID-19 (coronavirus)|website=www.isrctn.com}}</ref> is a large-enrollment [[clinical trial]] of possible treatments for people in the [[United Kingdom]] admitted to hospital with severe [[COVID-19]] infection.<ref name="RECOVERY Home">{{cite web |title=RECOVERY Trial |url=https://www.recoverytrial.net/ |access-date=17 June 2020}}</ref><ref name="BBC17June20">{{cite news |title=Coronavirus: Dexamethasone being used to treat NHS patients today |work=BBC News |date=17 June 2020 |url=https://www.bbc.co.uk/news/health-53077893 |access-date=17 June 2020}}</ref><ref name="NatBio 11May20" /> The trial was later expanded to [[Indonesia]], [[Nepal]] and [[Vietnam]].<ref>{{Cite web|title=International sites — RECOVERY Trial|url=https://www.recoverytrial.net/international|access-date=2021-05-17|website=www.recoverytrial.net}}</ref> The trial has tested ten interventions on adults: eight [[COVID-19 drug repurposing research|repurposed drugs]], one [[COVID-19 drug development|newly developed drug]] and [[antiserum|convalescent plasma]].<ref name="RECOVERY Home" />
 ==Treatments==
@@ Line 54: / Line 54: @@
 [[File:RECOVERY Trial Dexamethasone ventilated.jpg|thumb|right|Mortality over 28 days for 1007 COVID-19 patients on [[mechanical ventilation]] at time of randomisation: 324 patients who received [[dexamethasone]] (red) compared to 683 who received standard hospital care (black)<ref name="Paper 22June2020" />]]
-On 22 June 2020, preliminary results were published in a preprint showing that low-dose [[dexamethasone]] treatment reduced the death rate by one third in hospitalized people needing [[ventilator]]s due to severe COVID-19 infection, and by one fifth in people treated with [[oxygen therapy]]. There was no benefit (and the possibility of harm) among people who did not require oxygen.<ref name="Paper 22June2020">{{cite journal |author1=RECOVERY Collaborative Group |title=Effect of Dexamethasone in Hospitalized Patients with COVID-19 – Preliminary Report |url=https://www.medrxiv.org/content/10.1101/2020.06.22.20137273v1 |website=MedRXiv |year=2020 |doi=10.1101/2020.06.22.20137273 |s2cid=219965377 |access-date=23 June 2020|doi-access=free }}</ref> The preliminary report was subsequently published in ''[[The New England Journal of Medicine]]''.<ref name="NEJM-17July20">{{cite journal |vauthors=Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ | display-authors=6 |title=Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report |journal=New England Journal of Medicine |date=July 2020 |doi=10.1056/NEJMoa2021436 | pmid=32678530 | pmc=7383595 |doi-access=free }}</ref>
+On 22 June 2020, preliminary results were published in a preprint showing that low-dose [[dexamethasone]] treatment reduced the death rate by one third in hospitalized people needing [[ventilator]]s due to severe COVID-19 infection, and by one fifth in people treated with [[oxygen therapy]]. There was no benefit (and the possibility of harm) among people who did not require oxygen.<ref name="Paper 22June2020">{{cite journal |author1=RECOVERY Collaborative Group |title=Effect of Dexamethasone in Hospitalized Patients with COVID-19 – Preliminary Report |url=https://www.medrxiv.org/content/10.1101/2020.06.22.20137273v1 |journal=MedRXiv |year=2020 |pages=2020.06.22.20137273 |doi=10.1101/2020.06.22.20137273 |s2cid=219965377 |access-date=23 June 2020|doi-access=free }}</ref> The preliminary report was subsequently published in ''[[The New England Journal of Medicine]]''.<ref name="NEJM-17July20">{{cite journal |vauthors=Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ | display-authors=6 |title=Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report |journal=New England Journal of Medicine |date=July 2020 | volume=384 | issue=8 | pages=693–704 |doi=10.1056/NEJMoa2021436 | pmid=32678530 | pmc=7383595 |doi-access=free }}</ref>
 ====Impacts====
@@ Line 93: / Line 93: @@
 ===Azithromycin===
 In a news release on 14 December 2020, the chief investigators announced that they had found no benefit from azithromycin in patients hospitalised with COVID-19. 2582 patients had received azithromycin, and 5182 were randomised to usual care alone. 28-day mortality in both cohorts was 19%.<ref name="Azithromycin-20201214">{{cite web |author1=Peter Horby |author2=Martin Landray |title=RECOVERY trial finds no benefit from azithromycin in patients hospitalised with COVID-19 |url=https://www.recoverytrial.net/news/recovery-trial-finds-no-benefit-from-azithromycin-in-patients-hospitalised-with-covid-19 |publisher=RECOVERY Trial |date=14 December 2020}}</ref> These preliminary results were released as a preprint on the same day.<ref name="medRxiv-20201214">
-{{cite web
+{{cite journal
 |title=Azithromycin in Hospitalised Patients with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
 |url=https://www.medrxiv.org/content/10.1101/2020.12.10.20245944v1
 |access-date=14 December 2020
 |doi=10.1101/2020.12.10.20245944
-|date=14 December 2020}}
+|date=14 December 2020|last1=Horby
+|first1=Peter W.
+|last2=Roddick
+|first2=Alistair
+|last3=Spata
+|first3=Enti
+|last4=Staplin
+|first4=Natalie
+|last5=Emberson
+|first5=Jonathan R.
+|last6=Pessoa-Amorim
+|first6=Guilherme
+|last7=Peto
+|first7=Leon
+|last8=Campbell
+|first8=Mark
+|last9=Brightling
+|first9=Christopher
+|last10=Prudon
+|first10=Ben
+|last11=Chadwick
+|first11=David
+|last12=Ustianowski
+|first12=Andrew
+|last13=Ashish
+|first13=Abdul
+|last14=Todd
+|first14=Stacy
+|last15=Yates
+|first15=Bryan
+|last16=Buttery
+|first16=Robert
+|last17=Scott
+|first17=Stephen
+|last18=Maseda
+|first18=Diego
+|last19=Baillie
+|first19=J Kenneth
+|last20=Buch
+|first20=Maya H.
+|last21=Chappell
+|first21=Lucy C.
+|last22=Day
+|first22=Jeremy N.
+|last23=Faust
+|first23=Saul N.
+|last24=Jaki
+|first24=Thomas
+|last25=Jeffery
+|first25=Katie
+|last26=Juszczak
+|first26=Edmund
+|last27=Lim
+|first27=Wei Shen
+|last28=Montgomery
+|first28=Alan
+|last29=Mumford
+|first29=Andrew
+|last30=Rowan
+|first30=Kathryn
+|journal=MedRxiv
+|pages=2020.12.10.20245944
+|display-authors=1
+}}
 </ref>
 ===Convalescent plasma===
+In a news release on 15 January 2021, the chief investigators announced the closure of the convalescent plasma arm of the trial. Among 1873 reported deaths from 10,405 patients, the trial reported "no significant difference in the primary endpoint of 28-day mortality (18% convalescent plasma vs. 18% usual care alone; risk ratio 1.04 [95% confidence interval 0.95-1.14]; p=0.34)".<ref name="Plasma-20210115">{{cite web|last1=RECOVERY trial chief investigators|date=15 January 2021|title=Recovery trial closes recruitment for convalescent plasma treatment for patients hospitalised with COVID-19|url=https://www.recoverytrial.net/news/statement-from-the-recovery-trial-chief-investigators-15-january-2021-recovery-trial-closes-recruitment-to-convalescent-plasma-treatment-for-patients-hospitalised-with-covid-19|url-status=live|archive-url=|archive-date=|access-date=15 January 2021|website=}}</ref> The article with full results was published on 14 May 2021.<ref>{{Cite journal|date=2021-05-14|title=Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial (RECOVERY Collaborative Group)|url=https://linkinghub.elsevier.com/retrieve/pii/S0140673621008977|journal=The Lancet|language=en|pages=S0140673621008977|doi=10.1016/S0140-6736(21)00897-7|pmc=8121538|author1=RECOVERY Collaborative GroupAbaniObbinaOAbbasAliAAbbasFatimaFAbbasMustafaMAbbasiSadiaSAbbassHakamHAbbottAlfieAAbdallahNabeelNAbdelazizAshrafAAbdelfattahMohamedMAbdelqaderBushraBAbdoDavidDAbdulBasirBAbdul RasheedAlthafAAbdulakeemAjibodeAAbdul-KadirRezanRAbdulleAminaAAbdulmumeenAbdulfatahiAAbdul-RaheemRasheedRAbdulshukkoorNiyazNAbdusamadKulaKAbed El KhaleqYazeedYAbedallaMaiMAbeer Ul AmnaAbeer Ul AmnaAUAbernethyKatrinaKAboabaAdebankeAAbo-LeyahHaniHAbou-HaggarAhmedAAbouibrahimMahmoudMAbrahamMiriamMAbrahamTizzyTAbraheemAbraheemAAbramsJudithJAbuHyacinth-JohnHJAbu-ArafehAhmedAAbubackerSyed 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IbrahimAbdelAYoungEoinEYoungGailGYoungLouiseLYoungRichardRYousafzarAsfandAYoussoufSajedaSYousufAhmedAYuChrissieCYungBernardBYusefDanielDYusefSaidSYusufIntekhabIZafarAnna-SophiaASZagaloSilviaSZaherSuSZahoorAqsaAZakiKareemKZakirNabhanNZalewskaKasiaKZamalloaAneAZamanMohsinMZamanRaisaRZamanShakirSZamikulaJulieJZammitLouiseLZammit-MangionMarieMZarbLynnLZebrackiEstherEZehnderDanielDZeidanLisaLZelmanMarianMZhaoXiaobeiXZhengDonglingDZhuDoreenDZiaMadihaMZibdehOmarOZill-E-HumaRabiaRZinEi ThanktETZindondaVeronicaVZinkinEleanorEZinyembaVivianVZipitisChristosCZmierczakArkadiuszAZubirAzamAZuhaRoslinRZuhraNazNZulaikhaRashaRZulfikarSabrinaSZulloCarolCZuriaga-AlvaroAnaAZuurbierWillWZyengiShebaS|pmid=34000257}}</ref>
-In a news release on 15 January 2021, the chief investigators announced the closure of the convalescent plasma arm of the trial. Among 1873 reported deaths from 10,405 patients, the trial reported "no significant difference in the primary endpoint of 28-day mortality (18% convalescent plasma vs. 18% usual care alone; risk ratio 1.04 [95% confidence interval 0.95-1.14]; p=0.34)".<ref name="Plasma-20210115">{{cite web|last1=RECOVERY trial chief investigators|first=|date=15 January 2021|title=Recovery trial closes recruitment for convalescent plasma treatment for patients hospitalised with COVID-19|url=https://www.recoverytrial.net/news/statement-from-the-recovery-trial-chief-investigators-15-january-2021-recovery-trial-closes-recruitment-to-convalescent-plasma-treatment-for-patients-hospitalised-with-covid-19|url-status=live|archive-url=|archive-date=|access-date=15 January 2021|website=}}</ref> The article with full results was published on 14 May 2021.<ref>{{Cite journal|last=|first=|last2=|first2=|last3=|first3=|last4=|first4=|last5=|first5=|last6=|first6=|last7=|first7=|last8=|first8=|last9=|first9=|last10=|first10=|last11=|first11=|date=2021-05-14|title=Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial (RECOVERY Collaborative Group)|url=https://linkinghub.elsevier.com/retrieve/pii/S0140673621008977|journal=The Lancet|language=en|pages=S0140673621008977|doi=10.1016/S0140-6736(21)00897-7|pmc=8121538}}</ref>
 ===Tocilizumab===
-Tocilizumab significantly reduces the risk of death when given to hospitalised patients with severe COVID-19. 2022 patients allocated to Tocilizumab were compared to 2094 who received standard hospital care. "''596 (29%) of the patients in the tocilizumab group died within 28 days compared with 694 (33%) patients in the usual care group (rate ratio 0·86; [95% confidence interval [CI] 0·77 to 0·96]; p=0·007), an absolute difference of 4%.''" Receiving tocilizumab also increased the chance of discharge from hospital within 28 days.<ref name="Tocilizumab-20210211">{{cite web |title=Tocilizumab reduces deaths in patients hospitalised with COVID-19 |url=https://www.recoverytrial.net/news/tocilizumab-reduces-deaths-in-patients-hospitalised-with-covid-19 |website=Recovery Trial |access-date=11 February 2021 |date=11 February 2021}}</ref><ref name="BBC-20210211">{{cite web |author1=Michelle Roberts |title=Arthritis drug tocilizumab cuts deaths from Covid |url=https://www.bbc.co.uk/news/health-56024772 |website=BBC News Online |publisher=BBC |access-date=11 February 2021 |date=11 February 2021}}</ref><ref name="pmid33933194">{{cite journal | vauthors = Gupta S, Leaf DE | title = Tocilizumab in COVID-19: some clarity amid controversy | journal = Lancet | volume = 397 | issue = 10285 | pages = 1599–1601 | date = May 2021 | pmid = 33933194 | doi = 10.1016/S0140-6736(21)00712-1 | url = | doi-access = free }}</ref>
+Tocilizumab significantly reduces the risk of death when given to hospitalised patients with severe COVID-19. 2022 patients allocated to Tocilizumab were compared to 2094 who received standard hospital care. "''596 (29%) of the patients in the tocilizumab group died within 28 days compared with 694 (33%) patients in the usual care group (rate ratio 0·86; [95% confidence interval [CI] 0·77 to 0·96]; p=0·007), an absolute difference of 4%.''" Receiving tocilizumab also increased the chance of discharge from hospital within 28 days.<ref name="Tocilizumab-20210211">{{cite web |title=Tocilizumab reduces deaths in patients hospitalised with COVID-19 |url=https://www.recoverytrial.net/news/tocilizumab-reduces-deaths-in-patients-hospitalised-with-covid-19 |website=Recovery Trial |access-date=11 February 2021 |date=11 February 2021}}</ref><ref name="BBC-20210211">{{cite web |author1=Michelle Roberts |title=Arthritis drug tocilizumab cuts deaths from Covid |url=https://www.bbc.co.uk/news/health-56024772 |website=BBC News Online |publisher=BBC |access-date=11 February 2021 |date=11 February 2021}}</ref><ref name="pmid33933194">{{cite journal | vauthors = Gupta S, Leaf DE | title = Tocilizumab in COVID-19: some clarity amid controversy | journal = Lancet | volume = 397 | issue = 10285 | pages = 1599–1601 | date = May 2021 | pmid = 33933194 | doi = 10.1016/S0140-6736(21)00712-1 | pmc = 8084409 | url = | doi-access = free }}</ref>
 This result supports the earlier findings of the Remap-Cap trial on the effectiveness of Tocilizumab for patients in intensive care, and extends those findings to a wider group of patients.<ref name="Guardian-20210211">{{cite web |author1=Nicola Davis |title=Arthritis drug that helps Covid ICU patients has wider benefits, trial finds |url=https://www.theguardian.com/world/2021/feb/11/arthritis-drug-tocilizumab-found-to-help-covid-icu-patients-has-wider-benefits-trial-finds |website=Guardian News |publisher=The Guardian |access-date=11 February 2021 |date=11 February 2021}}</ref>