NIH halts trial of Covid-19 convalescent plasma in emergency department patients with mild symptoms: ‘Safe but no significant benefit’

‘The National Institutes of Health has halted a clinical trial evaluating the safety and effectiveness of COVID-19 convalescent plasma in treating emergency department patients who developed mild to moderate symptoms of COVID-19, the disease caused by the coronavirus SARS-CoV-2.

‘An independent data and safety monitoring board (DSMB) met on Feb. 25, 2021 for the second planned interim analysis of the trial data and determined that while the convalescent plasma intervention caused no harm, it was unlikely to benefit this group of patients. After the meeting, the DSMB recommended that the National Heart, Lung, and Blood Institute (NHLBI), part of NIH, stop enrolling new patients into the study. NHLBI did so immediately.’

Read here (NIH, Mar 2, 2021) 

Convalescent plasma did not improve patient outcomes compared with placebo group: Study

‘In a systematic review and meta-analysis published in JAMA, researchers evaluated treatment with convalescent plasma compared to standard of care or use of a placebo in randomized clinical trials (RCTs)—published through January 29, 2021. The researchers identified 10 total RCTs—4 published peer-reviewed studies and 6 unpublished studies—including a total of 11,782 COVID-19 patients. 

‘Overall, convalescent plasma did not significantly differ from placebo or standard of care for any of the major outcomes of interest: all-cause mortality, length of hospital stay, mechanical ventilation use, clinical improvement, clinical deterioration, and serious adverse events. The researchers noted that there was limited data available regarding clinical improvement, clinical deterioration, and serious adverse events in these studies.’ (Summary from John Hopkins Centre for Health Security newsletter of March 2)

Read here (JAMA Network, Feb 26, 2021)

Early high-titer plasma therapy to prevent severe Covid-19 in older adults

‘Background: Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered to hospitalized patients has been unsuccessful, perhaps because antibodies should be administered earlier in the course of illness.

‘Methods: We conducted a randomized, double-blind, placebo-controlled trial of convalescent plasma with high IgG titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adult patients within 72 hours after the onset of mild Covid-19 symptoms. The primary end point was severe respiratory disease, defined as a respiratory rate of 30 breaths per minute or more, an oxygen saturation of less than 93% while the patient was breathing ambient air, or both. The trial was stopped early at 76% of its projected sample size because cases of Covid-19 in the trial region decreased considerably and steady enrollment of trial patients became virtually impossible.

‘Results: A total of 160 patients underwent randomization. In the intention-to-treat population, severe respiratory disease developed in 13 of 80 patients (16%) who received convalescent plasma and 25 of 80 patients (31%) who received placebo (relative risk, 0.52; 95% confidence interval [CI], 0.29 to 0.94; P = 0.03), with a relative risk reduction of 48%. A modified intention-to-treat analysis that excluded 6 patients who had a primary end-point event before infusion of convalescent plasma or placebo showed a larger effect size (relative risk, 0.40; 95% CI, 0.20 to 0.81). No solicited adverse events were observed.

‘Conclusions: Early administration of high-titer convalescent plasma against SARS-CoV-2 to mildly ill infected older adults reduced the progression of Covid-19.’

Read here (NCBI-New England Journal of Medicine, Jan 6, 2021)

Early high-titer plasma therapy to prevent severe Covid-19 in older adults (New England Journal of Medicine, Jan 6, 2021)

‘We report the use of convalescent plasma in older adult patients early in the course of Covid-19. The administration of convalescent plasma with high titers of antibodies against SARS-CoV-2 to infected patients within 72 hours after the onset of symptoms reduced the risk of progression to severe respiratory disease by 48%. Although our trial lacked the statistical power to discern long-term outcomes, the convalescent plasma group appeared to have better outcomes than the placebo group with respect to all secondary end points. Our findings underscore the need to return to the classic approach of treating acute viral infections early, and they define IgG targets that facilitate donor selection...

‘In our randomized, controlled trial, the administration of high-titer convalescent plasma against SARS-CoV-2 to infected older adults within 72 hours after the onset of mild symptoms reduced the progression of Covid-19 to severe illness. This simple and inexpensive intervention can reduce demands on the health care system and may save lives. Early infusions of convalescent plasma can provide a bridge to recovery for at-risk patients until vaccines become widely available.’

Read here (New England Journal of Medicine, Jan 6, 2021)

Covid-19 blood plasma therapy has limited effect, study finds

‘It has been touted as a breakthrough treatment by Donald Trump, and there are hopes that blood plasma containing coronavirus antibodies may help British patients during the second wave of Covid-19 as well. But a study, which is published in the British Medical Journal (BMJ) on Friday, suggests “convalescent plasma” has only limited effectiveness and fails to reduce deaths or stop the progression to severe disease.

‘The research involved 464 adults with moderate Covid-19 who were admitted to hospitals in India between April and July. Approximately half received two transfusions of convalescent plasma, 24 hours apart, alongside standard care, while the control group received standard care only. One month later, 19% of those who received the plasma had progressed to severe disease or had died of any cause, compared with 18% in the control group. Plasma therapy did, however, seem to reduce symptoms, such as shortness of breath and fatigue, after seven days.’

Read here (The Guardian, Oct 23, 2020)

What the 'emergency' blood plasma debacle reveals: If the FDA’s emergency authorisations aren’t used responsibly, they could lose their power

‘The FDA previously came under fire for issuing an EUA for after Trump became fixated on the drug, which the agency later rescinded when the drug proved to be ineffective. With plasma, the agency has again issued an EUA following a loud and public campaign by the president based on little scientific evidence. The Trump administration is reportedly considering using the EUA process to fast-track a COVID-19 vaccine before the November election. “It just seems to be a pattern now,” says Jesse Goodman, a former chief scientist at the FDA now at Georgetown. “I’m very worried that this might happen with vaccines.” A controversial EUA for a vaccine could inflame fears that a vaccine is being rushed out.’

Read here (The Atlantic, August 27, 2020)

Evidence for convalescent plasma coronavirus treatment lags behind excitement

‘But so far, there’s little evidence that plasma actually helps patients, and the decision could confound efforts to study its effects, says former FDA commissioner Robert Califf, who now heads clinical policy and strategy at Verily and Google Health in South San Francisco, California... Convalescent plasma has been tested only in small trials without the statistical power to provide firm conclusions... “It’s a potential therapy that could work, and I don’t think it’s out of bounds to make it available” with an authorization, says Califf. “But we ought to be really emphasizing in public-service announcements that participation in randomized trials is a first priority.” 

[This story was written before the US Food and Drug Administration issued an emergency-use authorisation on August 23 to treat COVID-19 with convalescent plasma.]

Read here (Scientific American, August 24, 2020)

WHO cautious on Covid-19 plasma as US issues emergency authorisation

‘The World Health Organisation on Monday (Aug 24) was cautious about endorsing the use of recovered Covid-19 patients' plasma to treat those who are ill, saying that evidence that it works remains "low quality" even as the United States issued emergency authorisation for such therapies. So-called convalescent plasma, which has long been used to treat diseases, has emerged as the latest political flashpoint in the race to find therapies for Covid-19. The US Food and Drug Administration (FDA) on Sunday authorised its use after President Donald Trump blamed the agency for impeding the rollout of vaccines and therapeutics for political reasons.’

Read here (Reuters, August 24, 2020)

Why blood from coronavirus survivors could be a lifeline for the sick

A growing number of hospitals are investigating antibody testing and blood plasma therapy as a way to combat the new coronavirus in sick patients. WSJ’s Daniela Hernandez explains in a video.

View video here (Wall Street Journal, April 10, 2020)