Empyema, PleuralPhase 4VIETSNCT07886541
VATS or Intrapleural Enzymatic Therapy for Patients With Empyema.
A Phase 4 study testing VATS group and IET in people with Empyema, Pleural and Pleural Infections, run by Amsterdam UMC at 1 site in Netherlands.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Empyema, Pleural, Pleural Infections
- What is being tested?
- VATS group and IET
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 164 participants
- Where
- 1 siteNetherlands
- Study dates
- Oct 2026to Oct 2029
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 11Show fewer
- 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.
Who cannot join
- 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).
Show all 9Show fewer
- 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).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Amsterdam UMC
Amsterdam, 1081HV
Wilja de Jonge, MD, +31650063948, w.r.dejonge@amsterdamumc.nl
About this study
Official title: VATS or Intrapleural Enzymatic Therapy for patientS With Empyema (the VIETS Trial).
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.
Read the detailed description
In the Netherlands, each year 24.000 patients are hospitalized for pneumonia, 50% of which develop pleural effusion: fluid accumulation in the cavity between the lungs and the chest wall. In every 6-7 cases, this fluid gets infected with bacteria; parapneumonic pleural infection or empyema; leading to high morbidity and mortality (up to 30% in immunocompromised and/or frail patients). Parapneumonic pleural infection is associated with prolonged hospitalization, high healthcare costs and significant societal impact. Patients complain of pain, prolonged chest tube drainage, long hospital stays and long rehabilitations. Standard care of parapneumonic pleural infections consists of placement of a chest tube and antibiotic treatment. Approximately 50% of patients with a parapneumonic pleural infection can be treated successfully with this strategy. When standard care fails, two main treatment modalities are available in daily practice. One is IET (intrapleural enzymatic therapy), where fibrinolytic agents are inserted through the chest tube to dissolve the fibrin formed in the pleural fluid. The other modality is minimally invasive surgery by VATS (video assisted thoracoscopic surgery).
No consensus exists on which modality is superior in terms of clinical outcomes (mortality, length of hospital stay (LOS), etc) and cost-effectiveness, since no studies with head-to-head comparisons of IET and VATS have been published yet. This has led to extensive practice variation throughout hospitals in the Netherlands and to protracted treatment episodes. In a national survey on treatment of parapneumonic pleural infection among pulmonologists and thoracic surgeons in the Netherlands both IET and VATS were used in daily practice, but the heterogeneity in treatment approach and - results was substantial. The scarce literature on the subject to date appears to favour VATS in terms of LOS, but this is not supported by solid scientific evidence. Because of the frequent occurrence of parapneumonic pleural infection, the high mortality and morbidity and the lack of consensus about the best treatment modality, this subject has been identified as a knowledge gap by the national societies of both pulmonary surgeons and pulmonologists. Both IET and VATS are considered usual care in the Netherlands for patients with a parapneumonic pleural infection. This is reflected by international guidelines which advocate the use of either IET or VATS in patients who deteriorate despite initial treatment with chest tube drainage and intravenous antibiotics.
Since no studies with head-to-head comparisons of IET and VATS have been published yet; the investigators want to research what the optimal treatment modality is for patients with a parapneumonic pleural infection (not responding to initial treatment with antibiotics and chest tube drainage).
- Conditions
- Empyema, Pleural, Pleural Infections
- Being tested
- VATS group, IET
- Keywords
- Empyema, Pleural Infection, VATS, Intrapleural Enzymatic Therapy
- Medical subject headings
- Empyema, Pleural, Empyema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VATS groupProcedure or surgery
VATS procedure to remove the infected fluid and facilitate re-expansion of the infected lung.
IETDrug
Intrapleural Enzymatic Therapy Consisiting of Alteplase 10mg and DNase 5mg
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: IET |
What is being measured
The primary outcome is the main question the study is designed to answer.
Length of hospital stay
This is defined as the number of days from chest tube insertion to hospital discharge.
Measured: Within the first 30 days after chest tube insertion.
Secondary outcomes (13)
Duration of chest tube drainage
Number of days between chest tube insertion and removal of chest tube
Measured: 30 days
Delayed discharge days
The number of hospital days between completion of treatment and actual hospital discharge that are unrelated to the treatment of the parapneumonic pleural infection (e.g. awaiting nursing home placement, rehabilitation facility placement, home care arrangements, or other administrative or logistical delays).
Measured: 30 days
Re-intervention rates
The need for additional drainage procedures or surgery
Measured: 30 days
Re-admission rates
Need for re-admission
Measured: 30 days
Morbidity
Defined as any deviation from the expected clinical course, including complications and (serious) adverse events
Measured: 30 days
Mortality
Mortality (30-day and 1-year)
Measured: 30-day and 1-year mortality
Type of antibiotic therapy
Type of antibiotic therapy
Measured: Up to 3 months after initiation of antibiotic therapy
Duration of antibiotic therapy
Duration of antibiotic therapy (in days)
Measured: Up to 3 months after initiation of antibiotic therapy
Type of analgesic use
Type of analgesic use
Measured: 30 days
Duration of analgesic use
Duration of analgesic use (in days)
Measured: 30 days
Healthcare consumption costs
Healthcare consumption will be assessed using the iMTA Medical Consumption Questionnaire (iMCQ), an instrument designed to measure medical consumption, including contacts with healthcare providers, hospitalizations, medical procedures, medication use, and other healthcare services. The questionnaire will be used to assess healthcare consumption following randomization.
Measured: Through study completion (at 1, 3, 6, 9, and 12 months after randomization)
Productivity loss costs
Productivity losses will be assessed using the iMTA Productivity Cost Questionnaire (iPCQ), a standardized instrument for measuring productivity losses for use in economic evaluations of healthcare. The questionnaire will be used to assess productivity losses following randomization.
Measured: Through study completion (at 1, 3, 6, 9, and 12 months after randomization)
Health-related quality of life
Health-related quality of life will be assessed using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L). The questionnaire assesses five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has five response levels, ranging from no problems to extreme problems. Responses will be used to assess health-related quality of life.
Measured: Through study completion (at baseline, 1 week, 2 weeks, 1, 3, 6, 9, and 12 months after randomization)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2026
- Study startOct 2026 (estimated)
- Primary completionOct 2028 (estimated)
- Study completionOct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Empyema, PleuralStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 164 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC
- Sponsor type
- University, hospital or other
- Collaborators
- Amphia Hospital, Dijklander Ziekenhuis, Sint Franciscus Gasthuis, Maxima Medical Center, Noordwest Ziekenhuisgroep, Rijnstate Hospital, Spaarne Gasthuis, Leiden University Medical Center, UMC Utrecht, Haaglanden Medical Centre
- Responsible party
- Principal investigator, Prof. J.T. Annema, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07886541
- Sponsor's protocol ID
- 2026.0854
- Other IDs
- 2026-526289-25-00
- Acronym
- VIETS
- Status last verified
- Oct 2026
- First submitted
- 25 Sep 2026
- Last updated
- 26 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The individual participant data (IPD) can be made available upon request, provided that the proposed research question is relevant and is not being directly addressed or investigated by the research group. Any resulting publication will include the entire research group as co-authors.
Publications
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.
PubMed 35716828Roberts 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.
PubMed 37433578Rahman 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.
PubMed 21830966Scarci 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.
PubMed 26254467de 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.
PubMed 40040906de 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.
PubMed 41158359Bedawi 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.
PubMed 37820359Bedawi 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.
PubMed 36229045
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- VATS or Intrapleural Enzymatic Therapy for patientS With Empyema (the VIETS Trial).
- ClinicalTrials.gov ID
- NCT07886541
- Acronym / sponsor ID
- VIETS / 2026.0854
- Conditions
- Empyema, Pleural, Pleural Infections
- Keywords
- Empyema, Pleural Infection, VATS, Intrapleural Enzymatic Therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 164 participants (estimated)
- Lead sponsor
- Amsterdam UMCUniversity, hospital or other
- Collaborators
- Amphia Hospital, Dijklander Ziekenhuis, Sint Franciscus Gasthuis, Maxima Medical Center, Noordwest Ziekenhuisgroep, Rijnstate Hospital, Spaarne Gasthuis, Leiden University Medical Center, UMC Utrecht, Haaglanden Medical Centre
- Study start
- Oct 2026 (estimated)
- Primary completion
- Oct 2028 (estimated)
- Study completion
- Oct 2029 (estimated)
- First posted
- 21 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In the Netherlands, each year 24.000 patients are hospitalized for pneumonia, 50% of which develop pleural effusion: fluid accumulation in the cavity between the lungs and the chest wall. In every 6-7 cases, this fluid gets infected with bacteria; parapneumonic pleural infection or empyema; leading to high morbidity and mortality (up to 30% in immunocompromised and/or frail patients). Parapneumonic pleural infection is associated with prolonged hospitalization, high healthcare costs and significant societal impact. Patients complain of pain, prolonged chest tube drainage, long hospital stays and long rehabilitations. Standard care of parapneumonic pleural infections consists of placement of a chest tube and antibiotic treatment. Approximately 50% of patients with a parapneumonic pleural infection can be treated successfully with this strategy. When standard care fails, two main treatment modalities are available in daily practice. One is IET (intrapleural enzymatic therapy), where fibrinolytic agents are inserted through the chest tube to dissolve the fibrin formed in the pleural fluid. The other modality is minimally invasive surgery by VATS (video assisted thoracoscopic surgery).
No consensus exists on which modality is superior in terms of clinical outcomes (mortality, length of hospital stay (LOS), etc) and cost-effectiveness, since no studies with head-to-head comparisons of IET and VATS have been published yet. This has led to extensive practice variation throughout hospitals in the Netherlands and to protracted treatment episodes. In a national survey on treatment of parapneumonic pleural infection among pulmonologists and thoracic surgeons in the Netherlands both IET and VATS were used in daily practice, but the heterogeneity in treatment approach and - results was substantial. The scarce literature on the subject to date appears to favour VATS in terms of LOS, but this is not supported by solid scientific evidence. Because of the frequent occurrence of parapneumonic pleural infection, the high mortality and morbidity and the lack of consensus about the best treatment modality, this subject has been identified as a knowledge gap by the national societies of both pulmonary surgeons and pulmonologists. Both IET and VATS are considered usual care in the Netherlands for patients with a parapneumonic pleural infection. This is reflected by international guidelines which advocate the use of either IET or VATS in patients who deteriorate despite initial treatment with chest tube drainage and intravenous antibiotics.
Since no studies with head-to-head comparisons of IET and VATS have been published yet; the investigators want to research what the optimal treatment modality is for patients with a parapneumonic pleural infection (not responding to initial treatment with antibiotics and chest tube drainage).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| VATS / surgical group | Experimental | Procedure: VATS groupVideo-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. |
| Intrapleural Enzymatic Therapy (IET) | Active comparator | Drug: IETIntrapleural 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age ≥ 18 years with pneumonia and suspected parapneumonic pleural infection, evidenced by (both obligatory):
- Pleural fluid which is either
- 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).
Key exclusion criteria (9 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VATS groupVATS procedure to remove the infected fluid and facilitate re-expansion of the infected lung. | Procedure or surgery | VATS / surgical group |
| IETIntrapleural Enzymatic Therapy Consisiting of Alteplase 10mg and DNase 5mg | Drug | Intrapleural Enzymatic Therapy (IET) |
Primary outcome
Length of hospital stay
Time frame: Within the first 30 days after chest tube insertion.
This is defined as the number of days from chest tube insertion to hospital discharge.
13 secondary outcomes
Duration of chest tube drainage
Time frame: 30 days
Delayed discharge days
Time frame: 30 days
Re-intervention rates
Time frame: 30 days
Re-admission rates
Time frame: 30 days
Morbidity
Time frame: 30 days
Mortality
Time frame: 30-day and 1-year mortality
Type of antibiotic therapy
Time frame: Up to 3 months after initiation of antibiotic therapy
Duration of antibiotic therapy
Time frame: Up to 3 months after initiation of antibiotic therapy
Type of analgesic use
Time frame: 30 days
Duration of analgesic use
Time frame: 30 days
Healthcare consumption costs
Time frame: Through study completion (at 1, 3, 6, 9, and 12 months after randomization)
Productivity loss costs
Time frame: Through study completion (at 1, 3, 6, 9, and 12 months after randomization)
Health-related quality of life
Time frame: Through study completion (at baseline, 1 week, 2 weeks, 1, 3, 6, 9, and 12 months after randomization)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
- Background: PubMed 35716828Akulian 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.
- Background: PubMed 37433578Roberts 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.
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- Individual participant dataSharing planned: Yes. The individual participant data (IPD) can be made available upon request, provided that the proposed research question is relevant and is not being directly addressed or investigated by the research group. Any resulting publication will include the entire research group as co-authors.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing VATS group and IET in people with Empyema, Pleural and Pleural Infections, run by Amsterdam UMC at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wilja de Jonge, MD (+31650063948, w.r.dejonge@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Length of hospital stay (time frame: Within the first 30 days after chest tube insertion.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07886541, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.