Role of Medical Thoracoscopy in Pleural Infection (PROMPT Trial) (PROMPT)

Multicentre Prospective Comparative Study of Medical Thoracoscopy vs Standard of Care in the Management of Pleural Infection

The PROMPT study is testing whether an early keyhole procedure called Medical Thoracoscopy, which lets doctors look inside the chest and remove infected fluid, works better than current standard treatment (medicines to break up thick fluid) for people with pleural infection. About 170 patients in several hospitals will be randomly assigned to one of the two treatments, and researchers will see which approach results in fewer additional procedures-such as another drain or surgery-within 30 days, as well as how quickly people recover and whether they experience any complications. Everyone in the study receives high-quality care, and the results will help doctors better understand which treatment gives patients the best chance of recovering quickly and safely

Study Overview

• Status: Not yet recruiting
• Conditions: Pleural Infection; Pleural Infections and Inflammations; Pleural Infections
• Intervention / Treatment: Procedure: medical thoracoscopy; Procedure: Standard of Care

Detailed Description

Pleural infection, also known as empyema or complicated parapneumonic effusion, occurs when infected fluid collects in the space between the lung and the chest wall. This condition can cause severe illness, requiring hospital admission for urgent treatment. Standard treatment usually involves antibiotics and the insertion of a chest tube to drain the infected fluid. In many cases, doctors also use medications called fibrinolytics (current gold standard treatment), which are delivered directly into the chest to help break up thick or separated pockets of fluid. While this treatment is effective for many people, around one-third of patients still do not fully recover with the initial approach and end up needing additional procedures or surgery. Because of this, doctors are looking for better ways to treat pleural infection earlier and more effectively.

One promising option is Medical Thoracoscopy, a minimally invasive procedure performed under local anaesthetic and conscious sedation. Through a small incision, doctors insert a camera into the chest to directly see and treat the infection. They can remove thick or loculated fluid, release adhesions, clean the pleural cavity more thoroughly, and place a larger drain under direct vision. Previous observational studies have suggested that performing thoracoscopy early in the illness may reduce the need for surgery later on. However, high-quality research comparing this approach with current standard care is still limited, and existing studies have faced challenges such as delays in timing and the use of surrogate outcomes rather than clinical ones. For this reason, more reliable evidence is needed to understand whether early Medical Thoracoscopy truly offers better results than fibrinolyitics.

The PROMPT trial ("Prospective study on the Role Of Medical thoracoscopy versus standard care in Pleural infecTion") has been designed to answer this important question. The study will take place across different hospitals in Italy, all of which have experience managing pleural disease and performing thoracoscopy. A total of 170 adult patients who are admitted to hospital with pleural infection and need drainage will be invited to take part. Everyone who agrees to join the study will be randomly allocated-like the flip of a coin-to receive either early Medical Thoracoscopy or standard care. This randomisation ensures that the comparison between treatments is fair, balanced, and unbiased.

Participants will be randomised either in the Medical Thoracoscopy arm or in the standard of care arm (fibrinolytics) within 24 hours after treatment failure of chest drain and medical therapy (i.e. antibiotics). In those who will be randomised in the Medical Thoracoscopy group, doctors will enter the chest cavity using a thin camera, break down any pockets of infected fluid, remove pus or debris, and place a chest drain. All patients will receive standard antibiotic treatment + chest drain placement recommended by current medical guidelines. Participants in the Standard Care group will receive fibrinolytic therapy (based on the well-established MIST-2 protocol). Urokinase may be used at centres where tPA and DNase are not routinely accessible. Both groups will receive the same supportive treatments, such as pain relief, physiotherapy, and oxygen if needed.

The main goal of the PROMPT trial is to determine whether early Medical Thoracoscopy reduces the need for additional procedures within the first 30 days. Additional procedures may include another chest drain, another course of fibrinolytics, or referral to surgery if the infection does not improve. The study is also interested in other important outcomes such as length of hospital stay, whether patients eventually require surgery, pain levels after treatment, side effects or complications, and survival up to 90 days. These outcomes are patient-centred and reflect the aspects of care that matter most to people facing this serious illness.

To ensure safety, all participants will be monitored carefully throughout their hospital stay and during follow-up visits at 30 and 90 days. A Data Monitoring Committee-independent of the research team-will regularly review safety information. If unexpected problems arise or if one treatment proves clearly superior or harmful, the committee has the authority to recommend changes or even stop the trial early. Ethical approval will be obtained before the trial begins, and all participants will provide written informed consent after receiving clear explanations of the study.

Every patient's personal information will be handled securely and confidentially according to European data protection regulations (GDPR). Only authorised members of the research team will have access to identifying information, and any data used for analysis will be anonymised. After the main results are published, the researchers plan to share anonymised datasets with other scientists who request access for further non-commercial research, helping to advance medical understanding while protecting participant privacy.

The PROMPT trial is expected to run for a total of 24 months, including recruitment and follow-up. No commercial funding is involved, ensuring that the study is entirely independent. Once completed, the research team will publish the results in peer-reviewed scientific journals, present them at conferences, and provide a plain-language summary so participants and the public can understand the findings.

Ultimately, the PROMPT study aims to provide clear, high-quality evidence about the best early treatment for pleural infection. If early Medical Thoracoscopy proves more effective than standard care, it could improve recovery, reduce the need for surgery, shorten hospital stays, and enhance the overall quality of care for patients facing this serious and often debilitating condition.

• Study Type: Interventional
• Enrollment (Estimated): 170
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Federico Mei, MD; Phone Number: +0715965538; Email: f.mei@staff.univpm.it
• Study Contact Backup: Name: Francesca Gonnelli, MD; Phone Number: +393408579087; Email: francesca.gonnelli@pm.univpm.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

• Adults ≥ 18 years
• Clinical and radiological diagnosis of pleural infection (purulent, culture-positive, or pH < 7.2)
• Need of pleural drainage
• Able and willing to give informed consent

Exclusion criteria

• Chest drain in situ >24h before randomisation
• Post-traumatic pleural effusion
• Known allergy to fibrinolytic agents or contraindication to thoracoscopy
• Pregnancy or breastfeeding
• Life expectancy < 3 months from another illness
• Previous lung surgery (pneumonectomy) in the same side of pleural infection
• Previous pleurodesis in the same side of pleural infection
• Any contraindication to Medical thoracoscopy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Medical Thoracoscopy (MT); Performed under local anaesthesia and conscious sedation (anaesthesiologic assistance).; Procedures include evacuation of infected fluid, breakdown of adhesions, and partial decortication if required.; A 20 F or larger drain is inserted post-procedure and connected to an underwater seal.; Standard antibiotic therapy as per guidelines.	Procedure: medical thoracoscopy; This is a minimally invasive procedure performed to directly treat pleural infection by entering the pleural cavity through a small incision in the chest wall. It is carried out under local anaesthesia combined with conscious sedation. This means the patient remains comfortable and relaxed but does not require general anaesthesia. A trained chest physician or interventional pulmonologist performs the procedure, usually inside a dedicated interventional pulmonology or endoscopy suite. A small cut (usually 1-2 cm) is made on the side of the chest. Through this opening, the doctor inserts a rigid or semi-rigid thoracoscope-a thin tube equipped with a camera and light source. This allows direct visualisation of the pleural space, enabling the doctor to identify pockets of infected fluid, adhesions, or fibrinous strands that might prevent effective drainage.
Active Comparator: Standard of Care (SoC); • Intrapleural fibrinolytic therapy: tissue plasminogen activator (tPA) 10 mg + DNase 5 mg twice daily for 3 days (per MIST-2 protocol(2)), when available, otherwise Urokinase as per routine clinical practice (i.e., 100.000UI in single administration/two days).	Procedure: Standard of Care; The Standard of Care (SoC) for pleural infection in this trial consists of image-guided chest drainage and systemic antibiotics + fibinolytics. An image-guided chest drain of at least 12 French is inserted using ultrasound or CT to remove infected fluid from the pleural space. Antibiotics are administered according to current guidelines. Drain management and supportive care follow institutional standards, and additional procedures are permitted only if predefined criteria for treatment failure are met. To improve drainage, participants are given intrapleural fibrinolytics according to the MIST-2 protocol: tPA 10 mg plus DNase 5 mg twice daily for 3 days. If tPA/DNase is not available, urokinase may be used instead following local routine practice (typically 100,000 IU in a single daily dose for up to two days). Drain management and supportive care follow institutional standards, and additional procedures are permitted only if predefined criteria for treatment failure are met.; Other Names: Antibiotics + fibrinolytics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Further pleural interventions	Need for any further pleural procedure within 30 days (repeat thoracentesis or drainage, additional fibrinolytic course, or surgery).	from the randomization up to 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital length of stay	days from admission up to 90 days (end of the study)	from the randomization up to the end of study at 90 days
Surgical referral	Need for surgical thoracoscopy (VATS) up to 90 days (end of the study)	from the randomization to the end of study at 90 days
Mortality	30- and 90-day mortality up to 90 days (end of the study)	From the randomization at 30 and 90 days
Patient-reported pain	Pain reported as per VAS (visual analogue scale) from 0 to 10 up to 90 days (end of the study)	From the intervention up to 90 days (end of the study)
Procedure-related adverse events	pain requiring whichever analgesia, pneumothorax and/or prolonged/persistent air leak -5days-, bleeding requiring intervention, UTI admission, cellulitis or chest wall infection at the port/chest tube site requiring antibiotic therapy, clinically significant subcutaneous emphysema up to 90 days (end of the study)	From the day of intervention up to 90 days (end of the study)

Collaborators and Investigators

• Sponsor: Università Politecnica delle Marche

Publications and helpful links

General Publications

• Wang K, Yang L, Tian P, Tan F, Liu D, Li W. Medical thoracoscopy combined with intrapleural injection of urokinase for treatment of pleural infection-a multicenter, prospective, randomized controlled study: study protocol. Respir Res. 2025;26(1):21
• Roberts ME RN, Maskell NA, Bibby AC, Blyth KG, Corcoran JP, Edey A, Evison M, de Fonseka D, Hallifax R, Harden S, Lawrie I, Lim E, McCracken D, Mercer R, Mishra EK, Nicholson AG, Noorzad F, Opstad KS, Parsonage M, Stanton AE, Walker S. British Thoracic Society Guideline for pleural disease. Thorax. 2023;78:1-42.
• Kheir F, Thakore S, Mehta H, Jantz M, Parikh M, Chee A, et al. Intrapleural Fibrinolytic Therapy versus Early Medical Thoracoscopy for Treatment of Pleural Infection. Randomized Controlled Clinical Trial. Ann Am Thorac Soc. 2020;17(8):958-64.
• Najib M Rahman NAM, Alex West, Richard Teoh, Anthony Arnold, Carolyn Mackinlay, Daniel Peckham, Chris W H Davies, Nabeel Ali, William Kinnear, Andrew Bentley, Brennan C Kahan, John M Wrightson, Helen E Davies, Clare E Hooper, Y C Gary Lee, Emma L Hedley, Nicky Crosthwaite, Louise Choo, Emma J Helm, Fergus V Gleeson, Andrew J Nunn, Robert J O Davies. Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med. 2011;365(6):518-26.
• Gonnelli F, Bonifazi, M., Iommi, M. et al. . Italian Multicentre study on the management of pLeural infection and Empyema: IMPLE study. Respiratory Research. 2025(26):322.

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): March 31, 2029

Study Registration Dates

• First Submitted: March 26, 2026
• First Submitted That Met QC Criteria: April 21, 2026
• First Posted (Actual): April 24, 2026

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Trial; Medical Thoracoscopy; Pleural infection
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Signs and Symptoms; Inflammation; Anti-Infective Agents; Health Services Administration; Health Care Quality, Access, and Evaluation; Therapeutics; Drug Therapy; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Quality of Health Care; Quality Indicators, Health Care; Anti-Bacterial Agents; Standard of Care; Thrombolytic Therapy
• Other Study ID Numbers: PROMPT2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No