MIST4
Research type
Research Study
Full title
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
IRAS ID
1012038
Contact name
Najib Rahman
Contact email
Sponsor organisation
University of Oxford
Research summary
Pleural infection is a severe complication of pneumonia, where infected fluid collects around the lungs. Around 40 new cases are diagnosed daily in the UK, increasingly among the elderly. Standard treatment includes antibiotics, chest tube drainage under local anaesthetic, and a hospital stay of approximately two weeks. However, 20% of patients either die within a year or require surgery when initial treatment fails. Surgery, while effective, carries significant risks—particularly for older or frail patients—where mortality can reach 35%.
Two less invasive treatment options are now available: Intrapleural Enzyme Therapy (IET), which enhances fluid drainage via the chest tube, and Video-Assisted Thoracoscopic Surgery (VATS), a keyhole surgical approach. Both have shown promise, but their comparative effectiveness has never been tested in a large, direct trial. Currently, choice of treatment varies by hospital and clinician. Evidence suggests that delays in administering effective therapy result in poorer outcomes, including death and prolonged hospitalisation.
A prior feasibility study showed that patients were willing to be randomised to either IET or VATS and that both treatments could be delivered promptly. Patients in that study identified reducing death, repeat procedures, and hospital stay as top priorities.
We now plan a definitive randomised trial to compare early IET versus early VATS in 604 patients across UK hospitals. Participants will be randomly allocated to either treatment. The primary outcome will be the need for further treatment—a key concern for patients.
The study design has been shaped by insights from a patient focus group and interviews with participants from the earlier feasibility trial. The focus group will continue to advise during the study and support recruitment.Findings will be shared through peer-reviewed journals, scientific conferences, newsletters, and patient forums.
REC name
South Central - Hampshire B Research Ethics Committee
REC reference
26/SC/0028
Date of REC Opinion
26 Feb 2026
REC opinion
Further Information Favourable Opinion