REMAP-CAP Oseltamivir Results Explainer
A standard flu drug was given to the sickest patients in ICU. It turned out to be making them worse.
A major international trial has found that oseltamivir, sometimes sold under the name Tamiflu, appears to increase the risk of death in critically ill patients with influenza. Here's what it means, and what it doesn't.
Written by Australian investigators of the REMAP-CAP Trial: A/Prof Aidan Burrell, Prof Steve Webb and Prof Allen Cheng
For more than two decades, oseltamivir has been a go-to treatment for influenza
When oseltamivir – sold under the brand name Tamiflu – was first approved by the Therapeutic Goods Administration in September 2000 (internationally in 1999), it represented a genuine advance in treating flu. It works by blocking the influenza virus from replicating, and many studies showed it was safe and effective at shortening the duration of symptoms in people with mild to moderate illness – typically by about less than a day.
Over time, that evidence base for community use was extended, in many clinicians' minds and in treatment guidelines, to patients who were more seriously ill. It seemed reasonable: if oseltamivir helped people with mild flu, surely it would help those who were critically ill in an intensive care unit?
That assumption has now been tested. The results are not what most doctors expected.
The trial that asked the question
REMAP-CAP is a large international adaptive platform trial being run across 40 hospitals in Australia and involving more than 250 sites in over 20 countries around the world. Monash University is the sponsor of the trial in Australia, and the Australian and New Zealand Intensive Care Research Centre (ANZIC-RC) at Monash provides global project management for this major multinational effort.
Rather than testing a single drug in a single study, REMAP-CAP is able to test multiple treatments at once – adapting in real time as evidence accumulates. It has previously produced practice changing results in COVID-19 and other critical illnesses.
One of the questions we asked in REMAP-CAP was whether oseltamivir actually helps the sickest influenza patients – those admitted to an intensive care unit (ICU). Remarkably, despite oseltamivir's long history of use, no randomised controlled trial had tested its use in this specific population. The evidence that guided ICU practice was drawn from extending the results of trials in less unwell patients.
We randomly assigned critically ill patients aged 12 and over with confirmed influenza to receive either oseltamivir or no antiviral treatment.
An unexpected result
The trial was stopped when it met its pre-specified stopping criteria – meaning the evidence was clear enough that continuing without acting on it would have been unethical.
Among patients with severe influenza, around 20% of those who received oseltamivir died within 90 days. In the patients who did not receive oseltamivir, the figure was around 14%.
Put simply: in critically ill patients, not giving oseltamivir was associated with better survival.
It was not what most clinicians expected. And it matters – but only for a specific group of patients.These results apply only to patients aged 12 and over who are critically ill in an ICU with confirmed influenza. These results don’t provide evidence about:
- People with flu managed at home or in the community, where oseltamivir is well-studied and safe
- Patients hospitalised with flu but not in ICU, where the picture is less clear and remains under investigation
- Children under 12, where we do not yet have sufficient data
- Post-exposure prophylaxis – using oseltamivir to prevent infection in exposed individuals, including in aged care outbreak settings
The evidence evaluating oseltamivir's use in mild to moderate flu is substantial, and not impacted by this trial. If you have been prescribed oseltamivir for flu at home, you should continue taking it as directed.
If you have received oseltamivir in the past, there is no suggestion that you are likely to experience adverse health effects.
Why might oseltamivir harm patients in ICU?
We don't yet know how oseltamivir causes this impact in critically ill patients.
It might be that the drug is having unexpected effects on the immune system in critically ill patients, or that there are factors to do with the length of illness that impact on oseltamivir's effects; but we are still working to figure this out.
Importantly, these findings do not leave critically ill patients without treatment. Patients in intensive care with severe influenza receive many other important treatments, such as supplemental oxygen, breathing and organ support (including mechanical ventilation when needed) and antibiotics for secondary bacterial infections. They may also receive physiotherapy to help clear secretions, nutritional support, careful management of fluids and electrolytes, and measures to prevent weakness and blood clots.
Why did we go public before peer review?
Normally, research findings go through a lengthy peer-review process before they are published in a medical journal and become publicly available.
When we saw the results in March, the Australian influenza season was approaching and we worked rapidly to notify public health authorities. After discussion with the Commonwealth Chief Medical Officer, Australian ICUs were recommended to pause the use of oseltamivir in critically ill patients while we undertook final analysis and prepared to make the results public.
The manuscript was submitted for peer review and the results were presented at the next major international scientific meeting of critical care clinicians, the Critical Care Reviews meeting in Belfast on 10 June 2026.
We are confident in the quality of the data and the robustness of the statistical approach. This is one trial, independent review of the results is important and that process is underway.
A link to the published paper will be made available on the REMAP-CAP website.
What happens next
REMAP-CAP continues. We are still testing baloxavir (Xofluza) – a different antiviral medication – in hospitalised influenza patients, and results are not yet available. We are also continuing to investigate oseltamivir in other patient groups, including children and hospitalised adults outside the ICU.
In the meantime, the most important message for clinicians is straightforward: in the ICU, pause oseltamivir and continue with established supportive care. In the community, continue as before.
The best protection is still not getting flu in the first place
Vaccination remains the most effective tool we have against severe illness, hospitalisation and critical illness requiring intensive care.
Getting vaccinated before this flu season is the best thing most Australians can do to protect themselves and those around them.
About the ANZIC-RC
The Australian and New Zealand Intensive Care Research Centre (ANZIC-RC) is a collaboration of critical care researchers across Australia and New Zealand, united by the goal of improving clinical outcomes for patients requiring intensive care. The centre also identifies treatments and care regimes that are efficient, cost-effective, and sustainable. Established in 2006 and based at Monash University's School of Public Health and Preventive Medicine in Melbourne, we are supported by funding from the NHMRC and Monash University.
Our research portfolio spans large-scale clinical trials, observational studies, feasibility projects, health economics investigations, and qualitative research – including work on interventions such as oseltamivir in critically ill patients. We also offer a range of services to support other researchers, from subject area advice through to full project management.