The Fourth Multicentre Intrapleural Sepsis Trial (MIST-4) - a randomised clinical randomised effectiveness study comparing early video assisted thoracic surgery and early intrapleural enzyme therapy in adult patients with pleural infection
This study, called MIST-4, is looking at the best way to treat a serious lung infection where fluid builds up around your lungs. This often happens after pneumonia. Standard care includes antibiotics and draining the fluid, but sometimes this isn't enough, and surgery might be needed. Surgery can be risky, especially for older people. Researchers want to compare two main treatments: Intrapleural Enzyme Therapy (IET), which uses a medicine to help drain the fluid, and Video-Assisted Thoracoscopic Surgery (VATS), which is a keyhole surgery. Both have shown promise. This study aims to find out which one works better to reduce the need for more treatments, shorten hospital stays, and improve recovery for people with this condition.
At a glance
What is this study about?
When you have a lung infection, sometimes infected fluid can collect in the space outside your lungs, called the pleura. This is known as a pleural infection. It's a serious problem, and about 40 new cases are diagnosed every day in the UK, often affecting older people or those who are frail. Treatment usually involves antibiotics, draining the fluid with a tube in your chest, and a stay in hospital for about two weeks.
However, for about 20% of patients, this initial treatment doesn't fully work. They might need more treatment or even surgery. While surgery can be very effective, it carries risks, especially for older or weaker patients, where there's a higher chance of complications. Two newer, less invasive treatments are available: one uses special 'enzyme' medicines to help break down the fluid and make it easier to drain, and the other is a keyhole surgery that helps remove the infection.
Currently, doctors don't have clear guidance on which of these two treatments is best to use early on, and the choice can depend on the hospital. We know that getting the most effective treatment quickly can lead to a better recovery for patients. This study aims to compare these two options directly in a large number of patients across different UK hospitals to discover which one leads to the best outcomes, helping doctors make informed decisions for patients in the future.
Key takeaways
- Compares two treatments for lung infection: enzyme therapy vs. keyhole surgery.
- Aims to find the best early treatment to prevent further procedures.
- Looking for adults with infected fluid around their lungs after initial care.
- Both treatments are already used in the NHS, reducing unknown risks.
- Results will help doctors choose better treatments for patients in the future.
Who may be eligible?
This study is looking for adults aged 18 or over who have a pleural infection. This means you have infected fluid around your lungs that needs draining.
You might be suitable if your initial treatment with a chest drain hasn't fully cleared the fluid, meaning there's still a significant amount of fluid around your lungs according to scans. Also, the medical team will assess your overall health to make sure you are in a good enough condition to potentially have surgery, even if you have other health problems like kidney or heart issues.
Hover, you won't be able to join if you've already had a similar type of enzyme treatment or specific saline flushes for this current infection.
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 18 years old or older?
- Do you have an infection where fluid is around your lungs?
- Has your initial chest drain treatment not completely cleared the fluid?
- Are doctors assessing you as generally well enough for potential surgery?
- Have you not received enzyme treatment for this specific infection before?
What does participation involve?
If you join the study, you'll be randomly assigned to receive one of two treatments: either the enzyme therapy or keyhole surgery. This is like flipping a coin, so neither you nor your doctor can choose. The main goal is to see which treatment helps you avoid needing further treatments. Doctors will keep a close eye on you for any unexpected health problems or side effects. The study plans to run from May 2026 to October 2029.
Potential risks and benefits
Locations (1)
- -Approximate-, England
Common questions
What is a pleural infection?
It's when infected fluid builds up in the space surrounding your lungs, often after pneumonia, making it hard to breathe.
What is enzyme therapy?
It's a treatment that uses special medicines given through a chest tube to help break down and drain the fluid around your lungs.
What is keyhole surgery (VATS)?
It's a type of surgery where doctors make small cuts to insert tiny cameras and tools to remove infected fluid from around your lungs.
How long will the study last for me?
The study aims to evaluate your treatment outcomes, and you will be followed to see how well you recover, but the exact duration of your personal involvement will depend on your recovery.
Who is paying for this study?
The study is funded by the National Institute for Health and Care Research (NIHR) in the UK.
How to find out more
Ellie Daly
Always speak to your GP or specialist before deciding to take part in a study.
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