REMAP-CAP Finds Oseltamivir Ineffective in Critically Ill Influenza Patients
A recently published preprint on oseltamivir for influenza in the critically ill reports unexpected findings. In the study, adult patients admitted to ICU receiving either five or ten days of oseltamivir had higher 90-day mortality than those who received no antiviral treatment. The study was conducted within REMAP-CAP.
Oseltamivir is widely used to treat influenza, including in patients with severe disease. However, evidence specifically addressing its effectiveness in critically ill patients has historically been absent, with the supporting evidence coming from observational studies and trials in less severely ill patients.
The study included 442 critically ill patients aged 12 years and older with confirmed influenza. Participants were randomly assigned to three groups: five days of oseltamivir, ten days of oseltamivir, or no antiviral treatment. The study found that patients receiving either 5 or 10 days of oseltamivir had higher 90-day mortality than those receiving no antiviral treatment. The trial arms were stopped early after the predefined criteria for inferiority were met.
The REMAP-CAP findings provide an important contribution to the evidence base. They also illustrate how randomized clinical trials can challenge assumptions about established treatments and help identify where clinical practice may need to be reconsidered.
"These findings are surprising and demonstrate why high-quality randomised evidence remains essential, including for treatments that have been part of clinical practice for many years. This is a strong example of why sustainable clinical research infrastructure is so important. By embedding research within international clinical networks, we can generate evidence that directly challenges uncertainty in clinical practice and ultimately helps improve care for patients with infectious diseases". - Dr. Lennie Derde, Intensivist at UMC Utrecht and Ecraid CEO is REMAP-CAP’s EU Principal Investigator
An example of adaptive clinical research
Conducted within REMAP-CAP, an international adaptive platform trial designed to evaluate treatments for severe acute infections, the study’s flexible design allows multiple treatment strategies to be evaluated within a common trial infrastructure and enables interventions to be stopped when evidence indicates that they are unlikely to benefit patients.
While the investigation of baloxavir as an antiviral treatment for influenza continues, as well as the investigation of immunomodulatory therapies (tocilizumab and baricitinib) in another domain of the platform trial, participants are no longer exposed to this ineffective, and potentially harmful, intervention.
Looking ahead
The findings raise important questions about the optimal management of critically ill patients with influenza and underline the need for continued clinical research in this area.
As influenza continues to cause substantial morbidity and mortality globally, generating reliable evidence on how best to treat patients with severe disease remains an important research priority.
About
UMC Utrecht is the Sponsor for the trial in Europe and some countries outside Europe.
REMAP-CAP is supported by the ECRAID-Base project which has received funding from the EU Horizon 2020 research and innovation programme (grant number 965313).
For detailed information about the REMAP-CAP study, go to www.remapcap.eu or www.remapcap.org.