Information for healthcare professionals
REMAP-CAP is a global Bayesian adaptive platform trial that evaluates multiple interventions for hospitalised patients with respiratory tract infection. One treatment that REMAP-CAP is evaluating are influenza antivirals, including oseltamivir, a neuraminidase inhibitor that prevents the replication of the influenza virus.
Oseltamivir is widely used for the treatment of critically ill patients with influenza based on evidence from less sick patients, however evidence from randomised clinical trials about its efficacy in the critically ill is lacking. Critically ill patients include those patients, usually cared for in the intensive care unit, who are on organ supports such as non-invasive ventilation or mechanical ventilation, or who are receiving a vasopressor infusion.
At a scheduled adaptive analysis, oseltamivir interventions in the platform’s Influenza Antiviral Domain met a predefined statistical threshold for inferiority among critically ill patients aged 12 years or older. Consequently, recruitment to these interventions was closed. By day 90, 19.4% of critically ill participants who received oseltamivir had died, as compared to 13.7% of participants assigned to receive no antiviral. The probability of that oseltamivir was effective was less than 2%, and the probability that oseltamivir was harmful was greater than 98%.
These results indicate that, among critically ill patients (aged 12 or older) with confirmed influenza, treatment with oseltamivir was found to be ineffective in reducing 90-day mortality compared with no antiviral, and had a high probability of harm.
Preliminary results from this domain of REMAP-CAP were recently presented at the Critical Care Reviews conference. A recording of this presentation can be found by clicking here.
To read the Frequently Asked Questions, please visit the REMAP-CAP Global website:
https://www.remapcap.org/oseltamivir-clinician-faqs.
Information for the general public
REMAP-CAP is a global trial looking at many different treatments for severe lung infections, including severe influenza (flu). One of the treatments we tested in this trial is called oseltamivir (sometimes sold under the name Tamiflu). Oseltamivir is an anti-viral medication which stops the flu virus from multiplying in the body. Oseltamivir has been a standard treatment for flu for more than 20 years.
In this trial, adult patients with severe flu who needed to be admitted to Intensive Care Units (ICU) were randomly put into groups who were either given oseltamivir, or not given oseltamivir. All other parts of treatment were decided by the team caring for them.
Unexpectedly, we found that for these patients, NOT giving oseltamivir was linked with better outcomes (fewer deaths). These results suggest that patients with severe flu who need to be admitted to an ICU should not receive oseltamivir, even though it is currently part of standard care.
This was very surprising because there had been some studies suggesting that oseltamivir is safe, and may have a small benefit to patients. But almost all of these studies were for people who were not in hospital or an ICU.
It is important to note that these results are from only the sickest flu patients, who needed to be admitted to an ICU. There is evidence for the safe use of oseltamivir in the community (outside of hospital) to both prevent and treat flu, but we know that ICU patients are very different to less unwell patients.
These results highlight how important trials like REMAP-CAP are to test whether treatments are safe and effective, including treatments that are already widely used. We hope that these results will help improve the care of future patients who are critically unwell with flu.
To read the Frequently Asked Questions: please visit the REMAP-CAP Global wesbite:
https://www.remapcap.org/oseltamivir-general-public-faqs.