First patient randomised into ‘super donor’ plasma trial

The first UK patient has been treated in reopened trial which will seek to confirm evidence that plasma from recovered 'super donors’ benefits immunosuppressed people with coronavirus.

Convalescent plasma is the antibody-rich plasma from people who have recovered from the virus. It was found not to benefit patients overall during the landmark RECOVERY and REMAP-CAP trials, which were both supported by NHS Blood and Transplant.

Donated plasma However, detailed analysis of the REMAP-CAP subgroup data has found an 89% chance that convalescent plasma with very high antibody levels did benefit patients who are immunosuppressed by reducing the need to support organ failure. (1)(2)

This vulnerable patient group includes people with some immune disorders, and people with illnesses which require medication that weakens the immune system, such as people with cancer or organ transplants. Around 500,000 people in England are immunosuppressed, according to the APACHE definition. (3)

Following the re-opening, the first UK patient has been transfused in the past few days at Charing Cross Hospital, part of Imperial College Healthcare NHS Trust. (4)

More than 15 hospitals across all four countries of the UK have agreed to take part in the trial, using plasma supplied by donations to NHS Blood and Transplant, with more expected to join in future weeks.

Only plasma with a very high antibody threshold, which is about ten times the threshold used in the original trials, will be used. The plasma will only come from people who have had both coronavirus and the vaccine, as they were found to have the highest antibody levels and the broadest reactivity against viral variants. (5)

The highest antibody level recorded so far in the reopened trial came from a man in his 20s who had just over 100,000 units of antibodies per millilitre, a figure around 100 times higher than that typically seen during the first wave of coronavirus.

The plasma donations will come from the existing donor base and there is no public appeal for new donors.  Several hundred units are being donated at Birmingham and Twickenham. Further plasma will come from nearly 300 suitable units still in storage from the original trials. The units will be issued to participating hospitals on a named patient basis. (6)(7)

Steven George donating plasma One of the people who has donated for the new trial is bank manager Steven George, 55, of Bromsgrove in Birmingham, had COVID in October 2020. He then went on to have the vaccines and the booster.

He said: “I thought that donating was the least that I could do to help others. It’s very moving when you see the news coverage of people who are vulnerable, especially the children, so anything I can do is a positive.” 

Professor Lise Estcourt, head of NHSBT’s clinical trials unit, is the chair of the of reopened convalescent plasma domain of REMAP-CAP.

She said: “There’s a signal from REMAP-CAP that convalescent plasma can help immunosuppressed people but only if it comes from super donors with very high antibody levels.

“It would be a valuable treatment because some immunosuppressed people do not respond to the vaccine and monoclonal antibodies – which are often given to immunosuppressed people - may not work against emerging variants.

“It could also be of particular use in the developing world, where access to more expensive treatments is limited.

“Only a full, randomised controlled trial can provide a definite answer. We have now reopened the plasma arm of the trial to get enough data for a result either way.

“We welcome the chance to again support world leading research and we’re grateful to everyone donating.”  

Anthony Gordon is the UK Chief Investigator for REMAP-CAP. He is Professor of Anaesthesia and Critical Care at Imperial College London and a consultant in critical care at Imperial College Healthcare NHS Trust.

He said: “The REMAP-CAP trial was designed to be adaptive, providing high quality evidence to guide best treatments for severely ill patients with COVID-19 around the world.

“As we move to a different stage of the pandemic we are pleased to be able to provide that evidence to ensure high-risk patients continue to receive the right combination of treatments.” 

Press release notes

REMAP-CAP is a randomised, embedded, multi-factorial, adaptive platform trial for community-acquired pneumonia. More than 300 sites are participating in the REMAP-CAP trial across 21 countries. REMAP-CAP has been named by the Chief Medical Officers of the United Kingdom as a key clinical trial for COVID-19.   The REMAP-CAP is led in the UK by Imperial College Healthcare NHS Trust and Imperial College London.
The original convalescent plasma arm of the REMAP-CAP had 1980 participants. Of these 66 had an immunodeficiency and received convalescent plasma. 60 participants in the control group had an immunodeficiency.  For more details on the results and the possibility of subgroup benefit, see this article, this discussion section, and the REMAP-CAP domain protocol (PDF 867KB).
Apache (Acute Physiology and Chronic Health Evaluation) is a disease classification system.
The patient prefers to remain anonymous.
Of those eligible to donate, about 30% of people have antibody levels high enough to meet the new threshold. .
The reopened convalescent plasma arm trial will last until about 300 to 500 people have been treated in the UK and in other countries set to take part.  Each patient will receive two units of plasma.
In addition to REMAP-CAP, several studies have suggested convalescent plasma is effective for immunosupressed people. A review of the literature in April 2021 (Senefeld et al., 2021) identified 75 reports on immunosuppressed patients receiving convalescent plasma, there were 51 case reports and 23 case series, as well as one case-control study. In this case-control study 143 treated adult patients with haematological malignancies were compared to 823 untreated controls. After adjustment for potential confounding factors, convalescent plasma treatment was associated with improved 30-day mortality (hazard ratio, 0.60; 95% CI, 0.37-0.97). There New England Journal of Medicine has also published a new paper showing convalescent plasma is effective in reducing the progress of the disease in people treated early as outpatients.