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 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 three months. This equates to one life saved for every 33 patients treated with simvastatin. 2,684 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, Co-Director of the HRB Irish Critical Care-Clinical Trials Network 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 2,500 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, 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 in Ireland and globally” said Professor Alistair Nichol, Professor of Critical Care Medicine at UCD School of Medicine, Consultant at St Vincent’s University Hospital, Director of the Irish Critical Care-Clinical Trials Network and lead investigator and coordinator of the trial in Ireland. “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, the Health Research Board who funded the trial in Ireland and research staff in Ireland and globally who have contributed to advancing knowledge to inform the treatment of COVID-19 and continue to contribute to this ground-breaking trial.”
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 ICUs in early March 2020, and continues to evaluate multiple interventions for COVID-19, influenza, and other causes of severe respiratory infection.
Congratulations to UCD School of Medicine's Professor Alistair Nichol and all involved in these important studies.