Not yet recruitingPHASE3INTERVENTIONAL

COMparison Between Anakinra and Tocilizumab in NORSE - "COMBAT-NORSE"

This research trial, called COMBAT-NORSE, is investigating two existing medicines, anakinra and tocilizumab, for a very rare and serious brain condition known as NORSE (New-Onset Refractory Status Epilepticus). NORSE causes ongoing seizures in people who were previously healthy, and these seizures don't stop with standard treatments. Because NORSE can lead to serious long-term problems or even be life-threatening, doctors sometimes use anakinra or tocilizumab when other treatments haven't worked. However, it's not clear which drug is best or when is the ideal time to give it. This study aims to answer these important questions to help improve treatment for NORSE patients.

At a glance

Status

Not yet recruiting

Phase

PHASE3

Sponsor

Yale University

Enrolment target

438

Start

01 Jul 2026

Estimated completion

30 Sep 2030

New Onset Refractory Status Epilepticus New-Onset Refractory Status Epilepticus Febrile Infection-Related Epilepsy Syndrome (FIRES)

What is this study about?

This important research study, called COMBAT-NORSE, is looking for better ways to treat a very serious, but rare, brain condition known as NORSE (New-Onset Refractory Status Epilepticus). NORSE causes continuous seizures that don't respond to regular seizure medicines. These seizures can affect children and adults who were healthy before, and they often lead to long-term health problems or can even be life-threatening.

Currently, doctors sometimes use two existing medications, anakinra or tocilizumab, when the usual treatments for NORSE haven't worked. However, we don't have enough clear information to know which of these two drugs is more effective, or what the best time is to give them to a patient. This study wants to find these answers so that doctors can make better choices for people with NORSE.

The study will involve patients from many hospitals across different countries, including the UK, USA, Canada, Europe, and Asia. It's designed to compare anakinra and tocilizumab to see which one helps patients recover better. By gathering this information, researchers hope to improve the treatment and outlook for people affected by this challenging condition.

Key takeaways

The study aims to find the best existing drug (anakinra or tocilizumab) for NORSE.
NORSE is a serious seizure condition not helped by standard treatments.
Participants will receive one of the two study medications.
The study involves at least one year of follow-up and assessments.
Participation is voluntary, and you can withdraw at any time.
This research hopes to improve future treatment for NORSE patients.

Who may be eligible?

To join this study, participants must be at least 2 years old and have been generally healthy before their seizures started. They must have NORSE, which means they are having severe, ongoing seizures that haven't stopped with at least two different seizure medications. This applies even if doctors later find a specific cause for the seizures.

For some parts of the study, you might also need to meet extra requirements. For example, if you are being chosen randomly for treatment, your doctors must have already been considering anakinra or tocilizumab for your care, and your seizures must have started within the last 7 days.

There are also some reasons why you might not be able to join. These include having other serious illnesses like advanced cancer, severe kidney or liver problems, or poorly controlled diabetes. Also, if you have allergies to the study drugs, an active serious infection, or certain blood test results outside the normal range, you wouldn't be able to take part.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

Are you or the patient at least 2 years old?
Were you generally healthy before the seizures started?
Have you been diagnosed with NORSE (ongoing seizures not responding to standard care)?
Is your doctor already considering anakinra or tocilizumab for your treatment plan?
Did your current seizures start within the last 7 days (for random assignment)?
Do you have any serious underlying medical conditions like advanced kidney/liver disease or uncontrolled diabetes?

Answer every question to see your result.

What does participation involve?

If you decide to join the study, you'll be placed into one of two groups. In one group, if your doctor was already considering either anakinra or tocilizumab for you, you'll be randomly assigned to receive one of these medications within 7 days of your seizures starting. In the other group, if you couldn't be randomly chosen (perhaps because your seizures started more than 7 days ago), doctors will still follow your health closely to understand how treatment timing affects recovery.

Regardless of your group, you'll receive one of the study medications. You'll also have regular check-ups and surveys over a full year to monitor your progress. Some participants might be asked to continue follow-ups annually after the first year. You'll also have the option to take part in a 60-minute interview to share your or your family's experiences with NORSE; this is completely optional.

Potential risks and benefits

Taking part in this study may offer the benefit of potentially finding a more effective treatment for NORSE, a condition that currently has limited options. You will receive careful medical attention and monitoring throughout the study. However, like all medications, anakinra and tocilizumab can have side effects, which your doctor will discuss with you. Taking part in any research also involves some time commitment for appointments and assessments. It's important to remember that joining is completely your choice, and you are free to withdraw from the study at any time without affecting your usual medical care.

Locations (33)

Some site locations are approximate. We're improving this — please verify with the trial team before travelling.

Barrow Institute
Verified postcode
Phoenix, United States
Children's Hospital Colorado
Verified postcode
Aurora, United States
Yale New Haven Hospital
Verified postcode
New Haven, United States
Children's National (DC)
Verified postcode
Washington D.C., United States
University of Florida
Verified postcode
Gainesville, United States
University of Chicago
Verified postcode
Chicago, United States
Northwestern University
Verified postcode
Evanston, United States
Mass General (MGH)
Verified postcode
Boston, United States
Beth Israel Deaconess
Verified postcode
Boston, United States
Boston Children's Hospital
Verified postcode
Boston, United States
Mayo Clinic
Verified postcode
Rochester, United States
University of Nebraska
Verified postcode
Lincoln, United States

Common questions

What is NORSE?

NORSE is a rare and very serious brain condition where seizures keep happening and don't stop with regular seizure medicines. It usually affects people who were healthy before.

What are anakinra and tocilizumab?

These are two existing medicines that doctors sometimes use to treat certain inflammatory conditions. In this study, they are being tested to see if they can help stop the continuous seizures in NORSE.

Will I get a new medicine?

You will receive either anakinra or tocilizumab, which are both existing medications, not brand-new experimental drugs. Your doctor will discuss which one is planned for you if you join.

How long will the study last for me?

You will be followed for at least one year with regular check-ups and possibly annually thereafter. The initial treatment phase is typically within 7 days of your seizures starting.

Can I stop participating if I want to?

Yes, joining the study is completely voluntary. You can choose to stop participating at any time, and this will not affect the quality of your medical care.

How to find out more

Camalene Chrysostoum

camalene.chrysostoum@yale.edu 2037375851 Official trial record

Always speak to your GP or specialist before deciding to take part in a study.