Multicentre Intrapleural Sepsis Trial 3
Research type
Research Study
Full title
The third Multi-Centre Intra-Pleural Sepsis Trial (MIST-3): Early Video Assisted Thoracoscopic Surgery (VATS) or Intrapleural Enzyme Therapy (IET) in Pleural infection - a feasibility, randomised trial
IRAS ID
255746
Contact name
Najib Rahman
Contact email
Sponsor organisation
University of Oxford
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
2 years, 0 months, 0 days
Research summary
Research Summary
Pleural infection is a serious complication of pneumonia where infected fluid collects around the lung in a large abscess. It can affect anyone, and occurs in 40 patients every day in the UK. Treatment requires antibiotics and drainage of fluid using a chest tube inserted with local anaesthetic between the ribs, and admission to hospital for 2 weeks.
When these treatments fail, patients either die (about 20% of cases) or are referred for major surgery (a further 20%). Surgery is important when initial treatment fails, but has several side effects and is not an option for elderly and sick patients, where the death rate is 40%.
A new treatment (called Intrapleural Enzyme Therapy or IET) can be given through the chest tube early in treatment, which improves drainage and reduces the need for surgery and the time spent in hospital. Keyhole surgery is also now available to drain infected fluid (Video Assisted Thoracoscopic Surgery or VATS), and some people believe that this should occur early in treatment to prevent death and long hospital admissions, but this has not been proven. Early treatment with either IET or VATS may therefore improve care but we do not know the long-term effects (e.g. restriction in breathing) or impact on quality of life.
In this study, we will consult with patients to understand what factors are important to them when treating this disease. This will help us to understand what should be measured in a study to best improve care. We will conduct a study where patients are randomised (assigned by computer) to usual treatment (chest tube and antibiotics), early VATS or early IET. We will measure whether it is acceptable to patients to be randomised in this way and whether a larger study in the future is important and possible.
Lay summary of study results
Early treatment with medications injected via a chest tube (known as intrapleural enzyme therapy or IET) or early surgery may improve care for patients with pleural infection but we do not know if this has a meaningful impact on impact on patient outcomes. We conducted a study where patients are randomised (assigned by computer) to usual treatment (chest tube and antibiotics), early surgery or early IET.
The main objectives were to measure whether it is acceptable to patients to be randomised in this way and whether a larger study in the future is important and possible. Additionally, we consulted with patients to understand what factors are important to them when treating this disease.
Due to a fall in recruitment following the start of the COVID-19 pandemic, 4 months into the start of the trial recruitment, 60 participants were recruited and randomised, instead of the planned 75. MIST-3 screened 178 patients for suitability and out of the 110 suitable patients, we successfully recruited and randomised 60 participants (54.5% recruitment). Participant feedback from the qualitative interviews was very positive. There was only 1 (unrelated) serious adverse event and other side effects from the treatments were minimal.
Despite the challenges placed by the pandemic, the study was completed and met its success target (>50% recruitment and >80% remaining in the trial until their first follow up after discharge). We believe a larger, definitive trial is feasible based on high acceptance of randomisation by patients. The incidence of pleural infection will be higher outside the Covid19 pandemic (rates of pleural infection presenting to hospital were reduced by 33%).
A full report is underway for publication in a scientific journal. We will present the results to our patient expert group and the scientific community at national and international meetings.URL to summary results:
https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fdoi.org%252F10.1164%252Frccm.202305-0854OC%2FNBTI%2FIFu1AQ%2FAQ%2F8c56b6c2-9c73-495d-9e98-7b6697511c65%2F2%2FGyO53Hw-Ge&data=05%7C02%7Ccambridgeeast.rec%40hra.nhs.uk%7Cf0ec75dba48c4df8e9f608dc75aad117%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638514623716887375%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=%2BbCPGTXP1DeFYDEZZxFgXxhGVDywG6XngKs8t%2FVaZsQ%3D&reserved=0REC name
East of England - Cambridge East Research Ethics Committee
REC reference
19/EE/0174
Date of REC Opinion
28 Jul 2019
REC opinion
Further Information Favourable Opinion