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Largest trial of multiple treatments for critically ill adults with Covid-19 has revealed findings

The world’s largest trial of multiple treatments for critically ill adults with Covid-19 has revealed new findings about intravenous vitamin C and simvastatin.

corona virus under a microscope

The findings are part of the ongoing REMAP-CAP trial which is funded and supported by NIHR. The trial is led in the UK by researchers at Imperial College London and Queen’s University Belfast.

Vitamin C

Researchers studied over 2,500 critically and non-critically ill patients in hospitals in 20 countries. It involved bringing REMAP-CAP together with another trial LOVIT-COVID. Participants received high dose intravenous vitamin C infusion. This was 100 times the strength of ordinary vitamin C supplements available in high street stores. The findings show the treatment did not improve outcomes for patients.

This is the largest trial examining high-dose vitamin C in Covid-19. This part of the trial was stopped once researchers had evidence the treatment was not effective. A full analysis of the data later revealed it may even be harmful. Researchers say clinicians should not use intravenous vitamin C to treat Covid-19 patients.

Simvastatin

Simvastatin is a widely available and inexpensive drug. The study showed it has a high probability (96%) of improving outcomes for critically ill patients with Covid-19. There was a 92% chance of improving survival at 3 months. This equates to 1 life saved for every 33 patients treated with simvastatin. The study involved 2,684 critically ill patients at 141 hospitals in 13 countries. Researchers say the findings will help healthcare professionals improve treatment.

Flu treatments

REMAP-CAP is an international adaptive platform trial investigating treatments for hospitalised patients with respiratory tract infection. The trial began testing treatments for Covid-19 patients in ICUs in early March 2020.

The study team are continuing to study flu treatments. They are gearing up for the UK’s flu season. The £2.9 million NIHR-funded and delivered trial aims to use pandemic lessons to treat people hospitalised with severe flu. Currently, there is no clear evidence about which treatments are best for severe cases. Many people with flu get better on their own without needing hospital treatment. But it can make some people seriously ill and even be life-threatening.

Researchers aim to recruit several thousand children and adults hospitalised with severe flu from 150 UK hospitals. Multiple treatments are being tested. These include anti-viral treatments oseltamivir (also known as Tamiflu) and baloxavir. Plus steroids and anti-inflammatory drugs found to be effective against Covid-19. More treatments may be added in the future.

'Landmark results'

Professor Danny McAuley, Professor and Consultant in Intensive Care Medicine at the Royal Victoria Hospital and Queen's University Belfast and lead investigator for the Simvastatin Domain, said: "These results are really encouraging as they have shown that treatment with simvastatin is highly likely to improve outcomes in critically ill patients with Covid-19. This research will help healthcare professionals internationally to improve the treatment of patients with Covid-19."

Professor Lucy Chappell, Chief Executive of the NIHR, said: “These are really important findings providing new evidence on two widely available treatments to help us provide the best care and management for those critically ill with Covid-19. One treatment appears to be beneficial, while the other is ineffective and even potentially harmful. We recognise the huge contribution of patients, families, researchers and staff across the NHS who have played their part in this innovative NIHR-funded and supported platform trial. These teams are continuing to spearhead clinical research vital to the fight against Covid-19, which has already helped save thousands of lives worldwide.

“Learnings from the Covid-19 pandemic are vital as the trial has adapted to find new treatments for flu. As winter approaches, we ask all patients to consider how they can help us find better and more effective treatments for flu, which continues to be a serious illness for many. It is crucial that hospitals get involved and take part in the trial to help tackle this virus and reduce pressures on the NHS.”

Professor Anthony Gordon, REMAP-CAP UK Chief Investigator, from Imperial College London and Imperial College Healthcare NHS Trust, said: “To have both of these landmark results from REMAP-CAP published simultaneously is testament to the ability of this trial to efficiently evaluate multiple interventions. We want to thank all the patients, clinicians, and research staff who have contributed to advancing knowledge to inform the treatment of Covid-19, and continue to contribute to this ground-breaking trial.”

The trial is led by Imperial College London and Queen’s University Belfast. NIHR’s Clinical Research Network (CRN) is supporting the study. NIHR's Health Technology Assessment (HTA) Programme is funding the flu platform part of the study. The new results published simultaneously today (Wednesday, 25 October), in JAMA (vitamin C) and in the NEJM (simvastatin).

Read more on the REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community Acquired Pneumonia) trial website.

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