VATS or Intrapleural Enzymatic Therapy for Patients With Empyema.

NCT07886541 | Not Yet Recruiting Phase 4

• 2 other identifiers: 2026.08542026-526289-25-00
• Study Type: interventional
• Target: 164
• Locations: 0 countries
• Sites: N/A

Brief Summary

A parapneumonic pleural infection is a frequently encountered and serious medical emergency with high morbidity and mortality in specific patient groups (especially in the elderly and immunocompromised). The burden of disease is high; extensive hospital stays, reduced Health-Related Quality of Life (HR-QoL) and long times to return to daily activities or to work are reported by patients and in studies. Standard care of pleural infections consists of placement of a chest tube and antibiotics. It is estimated that approximately 50% of patients with a pleural infection can be treated successfully with this strategy. When standard care fails, two main treatment modalities are available. One is intrapleural enzymatic therapy (IET), where medication is inserted through the chest tube. The other modality is minimally invasive surgery by video-assisted thoracoscopic surgery (VATS). Although both modalities are extensively used, no consensus exits on which modality is superior or more cost-effective. This has led to extensive practice variation throughout hospitals in the Netherlands and to prolonged treatment episodes. The scarce literature on the subject to date appears to favor VATS in terms of treatment duration, but this is not supported by solid scientific evidence. The primary objective is to provide decisive evidence on which treatment modality is superior for the treatment of pleural infections. This evidence will help to guide future treatment decisions and will lead to optimal and cost effective treatment of pleural infections. In order to provide this evidence, the investigators aim to investigate which modality results in the shortest length of hospital stay (LOS). In addition, the investigators want to investigate which modality is superior in terms of patient-reported outcomes (PROMs), complications, re-interventions and mortality. The main trial endpoint is LOS during the first 30 days. This is defined as the time from the moment of chest tube insertion to the date of discharge.

Conditions

Empyema, Pleural; Pleural Infections

Keywords

Empyema; Pleural Infection; VATS; Intrapleural Enzymatic Therapy

Outcome Measures

Primary Outcomes (1)

• Length of hospital stay

  This is defined as the number of days from chest tube insertion to hospital discharge.

  Within the first 30 days after chest tube insertion.

Secondary Outcomes (13)

• Duration of chest tube drainage

  30 days

• Delayed discharge days

  30 days

• Re-intervention rates

  30 days

• Re-admission rates

  30 days

• Morbidity

  30 days

Study Arms (2)

VATS / surgical group

EXPERIMENTAL

Video-assisted thoracic surgery (VATS), is already commonly used in daily practice for the treatment of parapneumonic pleural infection. In this study, VATS should be commenced no later than 48 hours after randomization. The VATS will be performed through one to three ports, to the discretion of the operating surgeon. The pleural fluid should be drained, the thorax purified, and decortication must be performed if necessary. Preferably one chest tube is inserted at the end of the procedure, size 20-32 French. Pain management is by paravertebral/intercostal nerve block with ropivacaine 7.5%. Suction on the chest tube is applied until a maximum of 24 hours after surgery, and water seal should than be applied if the lung is fully expanded and drained fluid is \<400ml/24hr.

Procedure: VATS group

Intrapleural Enzymatic Therapy (IET)

ACTIVE COMPARATOR

Intrapleural enzymatic therapy (IET), refers to the instillation of fibrinolytic agents through a chest tube in order to facilitate the evacuation of infected pleural fluid. In the current study, the first dose of IET through the chest tube should be administered no later than 48 hours after randomization. Intrapleural therapy consists of two drugs: Alteplase 10mg and DNase 5mg. IET is administered twice daily through the chest tube and left in the thorax for one hour by blocking the chest tube. The drugs are prepared separately and administered concurrently, in random order. Only properly trained medical personnel is allowed to prescribe and perform the administration of IET. This dose, alteplase 10mg and DNase 5mg intrapleurally twice a day for six doses, will be administered through a chest tube in this study.

Drug: IET

Interventions

VATS group PROCEDURE

VATS procedure to remove the infected fluid and facilitate re-expansion of the infected lung.

VATS / surgical group

IET DRUG

Intrapleural Enzymatic Therapy Consisiting of Alteplase 10mg and DNase 5mg

Intrapleural Enzymatic Therapy (IET)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years with pneumonia and suspected parapneumonic pleural infection, evidenced by (both obligatory):
• Pleural fluid which is either
• Purulent
• Gram stain or culture positive
• Acidic (pH\<7.2)
• Low in glucose (\<2 mmol/L)
• AND
• Radiological suspicion of parapneumonic pleural infection (on either radiograph, ultrasound (US) or Computed Tomography-scan (CT-scan)), e.g. showing septations (US) or pleural contrast enhancement (CT)
• Fit for surgery (ie able to be ventilated on one lung during the procedure).
• Failure of standard care (consisting of a chest tube and antibiotics) as judged by the treating physician ≤ 24 h after chest tube insertion, considering: Radiology (significant residual pleural collections on imaging); Insufficient decrease of inflammatory markers (C-reactive protein (CRP) and white blood cell (WBC)); Clinical status of the patient (lack of improvement).
• Able to provide informed consent.

You may not qualify if:

• Patients not fit for surgery.
• Patients requiring direct surgery (e.g. dry tap). These are patients in which a non-surgical approach is considered to be not successful from the start. This decision will be made by combining the clinical status of the patient and the findings of the additional (radiological) investigations.
• Patients with a suspected or confirmed bronchopleural fistula.
• Need for more than two chest tubes at presentation.
• Any contraindication to IET (bleeding risk, allergy).
• A parapneumonic pleural infection with another cause than a pneumonia (e.g. infection after an intervention or after pulmonary/esophageal surgery, but also pneumonia related to obstruction due to lung cancer).
• Previous treatment of a parapneumonic pleural infection \<1 year ago, a history of pulmonary surgery on the same side of the parapneumonic pleural infection.
• Life expectancy \<3 months and/or suffer from a terminal illness.
• Patients who are pregnant or lactating (pregnancy status will be confirmed prior to randomisation for woman of childbearing potential).

Sponsors & Collaborators

• Amsterdam UMC: lead
• Amphia Hospital: collaborator
• Dijklander Ziekenhuis: collaborator
• Sint Franciscus Gasthuis: collaborator
• Maxima Medical Center: collaborator
• Noordwest Ziekenhuisgroep: collaborator
• Rijnstate Hospital: collaborator
• Spaarne Gasthuis: collaborator
• Leiden University Medical Center: collaborator
• UMC Utrecht: collaborator
• Haaglanden Medical Centre: collaborator

Related Publications (8)

• Akulian J, Bedawi EO, Abbas H, Argento C, Arnold DT, Balwan A, Batra H, Uribe Becerra JP, Belanger A, Berger K, Burks AC, Chang J, Chrissian AA, DiBardino DM, Fuentes XF, Gesthalter YB, Gilbert CR, Glisinski K, Godfrey M, Gorden JA, Grosu H, Gupta M, Kheir F, Ma KC, Majid A, Maldonado F, Maskell NA, Mehta H, Mercer J, Mullon J, Nelson D, Nguyen E, Pickering EM, Puchalski J, Reddy C, Revelo AE, Roller L, Sachdeva A, Sanchez T, Sathyanarayan P, Semaan R, Senitko M, Shojaee S, Story R, Thiboutot J, Wahidi M, Wilshire CL, Yu D, Zouk A, Rahman NM, Yarmus L; Interventional Pulmonary Outcomes Group. Bleeding Risk With Combination Intrapleural Fibrinolytic and Enzyme Therapy in Pleural Infection: An International, Multicenter, Retrospective Cohort Study. Chest. 2022 Dec;162(6):1384-1392. doi: 10.1016/j.chest.2022.06.008. Epub 2022 Jun 16.

  PMID: 35716828 BACKGROUND

• Roberts ME, Rahman NM, Maskell NA, Bibby AC, Blyth KG, Corcoran JP, Edey A, Evison M, de Fonseka D, Hallifax R, Harden S, Lawrie I, Lim E, McCracken DJ, Mercer R, Mishra EK, Nicholson AG, Noorzad F, Opstad K, Parsonage M, Stanton AE, Walker S; BTS Pleural Guideline Development Group. British Thoracic Society Guideline for pleural disease. Thorax. 2023 Jul;78(Suppl 3):s1-s42. doi: 10.1136/thorax-2022-219784. No abstract available.

  PMID: 37433578 BACKGROUND

• Rahman NM, Maskell NA, West A, Teoh R, Arnold A, Mackinlay C, Peckham D, Davies CW, Ali N, Kinnear W, Bentley A, Kahan BC, Wrightson JM, Davies HE, Hooper CE, Lee YC, Hedley EL, Crosthwaite N, Choo L, Helm EJ, Gleeson FV, Nunn AJ, Davies RJ. Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med. 2011 Aug 11;365(6):518-26. doi: 10.1056/NEJMoa1012740.

  PMID: 21830966 BACKGROUND

• Scarci M, Abah U, Solli P, Page A, Waller D, van Schil P, Melfi F, Schmid RA, Athanassiadi K, Sousa Uva M, Cardillo G. EACTS expert consensus statement for surgical management of pleural empyema. Eur J Cardiothorac Surg. 2015 Nov;48(5):642-53. doi: 10.1093/ejcts/ezv272. Epub 2015 Aug 7.

  PMID: 26254467 BACKGROUND

• de Jonge WR, Smits B, Ket JCF, Altenburg J, Annema J, Daniels JMA, Dickhoff C, van Dorp M, Braun J, Korevaar DA, Heineman DJ. Enzymatic therapy versus video-assisted thoracoscopic surgery for pleural infections: a systematic review and meta-analysis. ERJ Open Res. 2025 Mar 3;11(2):00619-2024. doi: 10.1183/23120541.00619-2024. eCollection 2025 Mar.

  PMID: 40040906 BACKGROUND

• de Jonge WR, Altenburg J, Dickhoff C, van Dorp M, Annema JT, Heineman DJ. Patient Preferences in empYema treatment (PAPY-study): are we investigating relevant outcomes for patients? J Thorac Dis. 2025 Sep 30;17(9):7297-7305. doi: 10.21037/jtd-2025-924. Epub 2025 Sep 26.

  PMID: 41158359 BACKGROUND

• Bedawi EO, Stavroulias D, Hedley E, Blyth KG, Kirk A, De Fonseka D, Edwards JG, Internullo E, Corcoran JP, Marchbank A, Panchal R, Caruana E, Kadwani O, Okiror L, Saba T, Purohit M, Mercer RM, Taberham R, Kanellakis N, Condliffe AM, Lewis LG, Addala DN, Asciak R, Banka R, George V, Hassan M, McCracken D, Sundaralingam A, Wrightson JM, Dobson M, West A, Barnes G, Harvey J, Slade M, Chester-Jones M, Dutton S, Miller RF, Maskell NA, Belcher E, Rahman NM. Early Video-assisted Thoracoscopic Surgery or Intrapleural Enzyme Therapy in Pleural Infection: A Feasibility Randomized Controlled Trial. The Third Multicenter Intrapleural Sepsis Trial-MIST-3. Am J Respir Crit Care Med. 2023 Dec 15;208(12):1305-1315. doi: 10.1164/rccm.202305-0854OC.

  PMID: 37820359 BACKGROUND

• Bedawi EO, Ricciardi S, Hassan M, Gooseman MR, Asciak R, Castro-Anon O, Armbruster K, Bonifazi M, Poole S, Harris EK, Elia S, Krenke R, Mariani A, Maskell NA, Polverino E, Porcel JM, Yarmus L, Belcher EP, Opitz I, Rahman NM. ERS/ESTS statement on the management of pleural infection in adults. Eur Respir J. 2023 Feb 2;61(2):2201062. doi: 10.1183/13993003.01062-2022. Print 2023 Feb.

  PMID: 36229045 BACKGROUND

MeSH Terms

Conditions

Empyema, Pleural; Empyema

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Suppuration; Pleural Diseases; Respiratory Tract Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Wilja de Jonge, MD

CONTACT

+31650063948; w.r.dejonge@amsterdamumc.nl

Josje Altenburg, MD, PhD

CONTACT

+31207323099; j.altenburg@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. MD. PhD

Study Record Dates

• First Submitted: September 25, 2026
• First Posted: October 21, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2029
• Last Updated: October 21, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: The IPD and supporting information will be available upon reasonable request following publication of the main study, with no predefined end date, provided that the proposed research question is relevant and is not already being addressed or investigated by the research group.
• Access Criteria: IPD and supporting information will be made available upon reasonable request to researchers proposing a scientifically relevant research question that is not directly addressed or currently being investigated by the research group. Requests must include a research proposal outlining the objectives and planned analyses. The research group will review each request to assess its scientific relevance, methodological appropriateness, and potential overlap with ongoing research. Approved requests will be granted access subject to agreement on the conditions of data use. Requests should be submitted directly to the research group. Any resulting publication will include the entire research group as co-authors.