{"id":39928,"date":"2021-02-24T07:14:38","date_gmt":"2021-02-24T07:14:38","guid":{"rendered":"https:\/\/i-base.info\/htb\/?p=39928"},"modified":"2021-02-26T14:37:33","modified_gmt":"2021-02-26T14:37:33","slug":"uk-recovery-study-reports-no-benefit-against-covid-19-from-convalescent-plasma-limited-results-complicate-findings","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/39928","title":{"rendered":"No benefit from convalescent plasma in UK RECOVERY study: limited results restrict implications for COVID-19"},"content":{"rendered":"
\n

<\/span><\/strong>Simon Collins, HIV i-Base<\/span><\/strong>
\n<\/span><\/strong><\/p>\n<\/div>\n

\n

On 15 January 2021, the UK RECOVERY study reported top-line results showing no benefit from using convalescent plasma as a treatment for COVID-19. Also, that further enrollment to this arm was stopped based on a recommendation from the Data Monitoring Committee (DMC) the day before. [1]<\/span><\/strong><\/p>\n<\/div>\n

\n

However, only three days earlier, the investigators had issued a statement that \u201cstrongly encouraged continuing recruitment\u201d for low risk participant – based on the DMC review a week earlier. The suggests that either significant changes occurred during one week or a disconnect between the investigators and the DMC. [2]<\/span><\/p>\n<\/div>\n

\n

Now, more than a month later, no further details have been released and the pre-review paper is still not published. Also, although the press statement refers to the protocol for the RECOVERY study being available online, the only reference to convalescent plasma is a listing as a new treatment (in May 2020). [3]<\/span><\/p>\n<\/div>\n

\n

The press release reported 1873 deaths among 10,406 participants. There was no difference in the primary endpoint of 28-day mortality with 18% mortality in each arm: risk ratio 1.04 (95%CI: 0.95 to 1.14), p=0.34.\u00a0<\/span><\/p>\n<\/div>\n

\n

No details were given on the participants, time to treatment, antibody titre, numbers included in the analysis or how many were still in follow-up.<\/span><\/p>\n<\/div>\n

\n

Dosing information from the trial register includes that a single<\/span> unit of convalescent plasma (275 mls +\/\u2013 75 mls IV) was given on day one (as soon as possible after randomisation) and another on day two (with a minimum of 12 hour interval between the first and second units). [4]<\/p>\n<\/div>\n

\n

As background, although other early studies reported conflicting results from using convalescent plasma, [5] several larger studies highlighted the importance of perhaps only using high-titre plasma in early infection. <\/span><\/p>\n<\/div>\n

\n

In August 2020, a large open label US expanded access programme with more than 35,000 participants reported reductions in both 7- and 30-day mortality with early use (within 3 days vs >4 days after diagnosis) and greater IgG antibody levels in the transfused plasma. In this study, 52% of participants were in ICU and 27% were on mechanical ventilation. [6]\u00a0<\/span><\/p>\n<\/div>\n

\n

Shortly afterwards, in October 2020, a large randomised study (PLACID) reported no benefit from convalescent plasma, but included the possibility that using a high-titre plasma earlier in infection might be more effective. [7] <\/span><\/p>\n<\/div>\n

\n

More recently, a study published in January in the NEJM reported that early use of high-titre convalescent plasma was associated with a 48% reduction in the risk of developing severe respiratory disease. [8]<\/span><\/p>\n<\/div>\n

\n

This double-blind, placebo-controlled study randomised 160 participants at high risk of progression due to age and\/or comorbidities at multiple sites in Argentina. The primary endpoint was defined as developing a respiratory rate\u00a0><\/u>30 breaths per minute, oxygen saturation <93% on ambient air, or both.<\/span><\/p>\n<\/div>\n

\n

The primary endpoint was reached in 16% vs 31% participants (n=13 vs 25) in the active vs placebo arms respectively: relative risk 0.52 (95%CI: 0.29 to 0.94), p=0.03). This study used a <\/span>single 250 mL infusion with an IgG titer greater than 1:1000 against SARS-CoV-2 spike (S) protein.<\/span><\/p>\n<\/div>\n

\n

comment<\/h3>\n<\/div>\n
\n

The results from this high-profile study have received minimal press coverage, certainly compared to results with other repurposed drugs. <\/span><\/strong><\/p>\n<\/div>\n

\n

As well as being disappointing, withholding further details in the press release complicates use of the results in current clinical practice and in ongoing studies – and a paper in CID last July criticised the RECOVERY study for doing this previously. [9]<\/span><\/strong><\/p>\n<\/div>\n

\n

In this case, however, further details are particularly important to understand whether the study design was adapted to only use high-titre plasma in early infection – also recently recommended by the US FDA. [10]<\/span><\/strong><\/p>\n<\/div>\n

\n

If not, then in addition to potentially contributing to poor outcomes for the participants, it might be premature to conclude that the question of using convalescent plasma has<\/span><\/strong> been answered.<\/span><\/strong><\/p>\n<\/div>\n

\n

References<\/p>\n<\/div>\n

\n
    \n
  1. Statement from the RECOVERY trial chief investigators. RECOVERY trial closes recruitment to convalescent plasma treatment for patients hospitalised with COVID-19. (15 January 2021).
    \n<\/span>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<\/a><\/span><\/li>\n
  2. Statement from the RECOVERY trial chief investigators. Update on recruitment to convalescent plasma and tocilizumab treatment arms.
    \n    https:\/\/www.recoverytrial.net\/news\/update-on-recruitment-to-convalescent-plasma-and-tocilizumab-treatment-arms-statement-from-the-recovery-trial-chief-investigators<\/a><\/span><\/li>\n
  3. Study Protocol. Randomised Evaluation of COVID-19 Therapy (RECOVERY) study.
    \n    https:\/\/www.recoverytrial.net<\/a><\/li>\n
  4. clinicaltrials.gov. Randomised Evaluation of COVID-19 Therapy (RECOVERY) study. NCT04381936.
    \n    https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04381936<\/a><\/li>\n
  5. Convalescent plasma therapy for COVID-19. HTB (1 June 2020).
    \n    https:\/\/i-base.info\/htb\/38022<\/a><\/span><\/li>\n
  6. Convalescent plasma: randomised controlled study finds no benefit in moderate stage COVID-19. HTB (11 November 2020).
    \n    https:\/\/i-base.info\/htb\/39247<\/a><\/li>\n
  7. Joyner MJ et al. Effect of convalescent plasma on mortality among hospitalized patients with COVID-19: initial three-month experience. Ahead of peer review. DOI:\u00a010.1101\/2020.08.12.20169359. (12 August 2020).
    \n    https:\/\/www.medrxiv.org\/content\/10.1101\/2020.08.12.20169359v1<\/a><\/li>\n
  8. Libster R et al. Early high-titer plasma therapy to prevent severe Covid-19 in older adults. NEJM. DOI: 10.1056\/NEJMoa2033700. (6 January 2021).
    \n    https:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMoa2033700<\/a><\/li>\n
  9. Siedner MJ and Gandhi RT. Proposing minimum requirements for announcing clinical trial results during the COVID-19 pandemic. Clinical Infectious Diseases, ciaa945. DOI: 10.1093\/cid\/ciaa945. (8 July 2020).
    \n    https:\/\/academic.oup.com\/cid\/advance-article\/doi\/10.1093\/cid\/ciaa945\/5868929<\/a><\/li>\n
  10. FDA. Investigational covid-19 convalescent plasma\u2014emergency INDs.\u00a0(4 February 2021).
    \n    https:\/\/www.fda.gov\/vaccines-blood-biologics\/investigational-new-drug-ind-or-device-exemption-ide-process-cber\/investigational-covid-19-convalescent-plasma-emergency-inds<\/a>
    \n    https:\/\/www.fda.gov\/media\/141477\/download<\/a> (PDF letter)<\/li>\n<\/ol>\n

    This article was first posted on 6 February 2021.<\/em><\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

    Simon Collins, HIV i-Base On 15 January 2021, the UK RECOVERY study reported top-line results showing no benefit from using convalescent plasma as a treatment for COVID-19. Also, that further enrollment to this arm was stopped based on a recommendation …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[283,278],"tags":[],"class_list":["post-39928","post","type-post","status-publish","format-standard","hentry","category-covid-19-investigational-drugs","category-covid-19"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/39928","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=39928"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/39928\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=39928"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=39928"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=39928"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}