Global platform study presents results to guide care of severely ill patients with COVID-19 using routinely available drugs

The world’s largest trial of multiple interventions for critically ill adults with COVID-19 has simultaneously released results about two of its treatments, vitamin C and simvastatin.

Published today in JAMA and NEJM, and presented at the European Society of Intensive Care Medicine in Milan, the studies are part of the ongoing Randomized Embedded Multifactorial Adaptive Platform for Community Acquired Pneumonia (REMAP-CAP) trial.

Simvastatin, a widely available and inexpensive drug that is included on the WHO (World Health Organization) list of essential medicines, was shown to have a high probability (96%) of improving outcomes (a combination of survival and length of time patients need support in an intensive care unit) when started as a treatment for critically ill patients with COVID-19, and a 92% chance of improving survival at 3 months. This equates to one life saved for every 33 patients treated with simvastatin. 2684 critically ill patients were included at 141 hospitals across 13 countries.

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 of REMAP-CAP 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."

Vitamin C is widely available around the world and was used in some settings for the treatment of COVID-19. Through harmonising two clinical trials – REMAP-CAP and LOVIT-COVID – over 2500 patients in 20 countries took part, including both critically ill and non-critically ill patients with COVID-19 in hospital. It was shown that high dose vitamin C did not improve outcomes for patients. This is the largest trial examining high-dose vitamin C in COVID-19 and provides evidence that high-dose vitamin C is not beneficial and suggests a high probability that it may be harmful.

Dr Neill Adhikari, co-lead investigator for the LOVIT-COVID trial and of the Vitamin C Domain of REMAP-CAP, said “harnessing the power of global collaboration, the harmonised REMAP-CAP and LOVIT-COVID trials have investigated vitamin C, a potential therapy for COVID-19, and have shown it to be ineffective and probably harmful. The results from this trial suggest that the use of vitamin C in hospitalised Covid-19 patients should be de-adopted.” Dr François Lamontagne, co-lead investigator of these trials, added “The results underscore the health and economic benefits of identifying and abandoning readily available interventions that are ineffective and potentially harmful to patients.”

Through this global initiative, combining clinical trial data and recruiting patients from countries around the world, including Aotearoa New Zealand, this model of research continues to produce important evidence for the clinical communities. “These findings may have important implications for the treatment of the sickest patients with COVID-19” said Dr Tom Hills, Medical Research Institute of New Zealand (MRINZ) COVID-19 Programme Lead and New Zealand REMAP-CAP investigator. “To have both of these 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 here in New Zealand, and worldwide, who have contributed to advancing knowledge to inform the treatment of COVID-19, and who continue to contribute to this ground-breaking trial,” says Dr Hills.

REMAP-CAP is a global adaptive platform trial investigating multiple treatments for hospitalised patients with respiratory tract infection. The trial mobilised to evaluate specific treatments for COVID-19 patients in Intensive Care Units in early March 2020, and continues to evaluate multiple interventions for COVID-19, influenza, and other causes of severe respiratory infection.