A Phase 4 interventional study of VATS group and IET in Empyema, Pleural and Pleural Infections, sponsored by Amsterdam UMC. Not yet recruiting. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-21.
Sponsored by Amsterdam UMC · Phase 4, Interventional, and Treatment
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.
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).
31 studies on the registry are indexed under Empyema, Pleural; 11 are open to participants now.
This study's planned enrollment of 164 is above the median of 70 across 23 interventional studies indexed under Empyema, Pleural.
Browse Empyema, Pleural studies →Amsterdam UMC is the lead sponsor of 10 studies on the registry; 9 are open to participants now.
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Pleural fluid which is either
AND
Exclusion Criteria:
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), 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
VATS procedure to remove the infected fluid and facilitate re-expansion of the infected lung.
Intrapleural Enzymatic Therapy Consisiting of Alteplase 10mg and DNase 5mg
Length of hospital stay
This is defined as the number of days from chest tube insertion to hospital discharge.
Time frame: Within the first 30 days after chest tube insertion.
Duration of chest tube drainage
Number of days between chest tube insertion and removal of chest tube
Time frame: 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).
Time frame: 30 days
Re-intervention rates
The need for additional drainage procedures or surgery
Time frame: 30 days
Re-admission rates
Need for re-admission
Time frame: 30 days
Morbidity
Defined as any deviation from the expected clinical course, including complications and (serious) adverse events
Time frame: 30 days
Mortality
Mortality (30-day and 1-year)
Time frame: 30-day and 1-year mortality
Type of antibiotic therapy
Type of antibiotic therapy
Time frame: Up to 3 months after initiation of antibiotic therapy
Duration of antibiotic therapy
Duration of antibiotic therapy (in days)
Time frame: Up to 3 months after initiation of antibiotic therapy
Type of analgesic use
Type of analgesic use
Time frame: 30 days
Duration of analgesic use
Duration of analgesic use (in days)
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Through study completion (at baseline, 1 week, 2 weeks, 1, 3, 6, 9, and 12 months after randomization)
No study locations are listed for this record.
Plan to share: 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.
Supporting information: Study protocol, Statistical analysis plan
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.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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Amsterdam UMC