VATS or Intrapleural Enzymatic Therapy for patientS With Empyema (the VIETS Trial).
| Registry | NCT07886541, acronym VIETS |
|---|---|
| Status | Not yet recruiting |
| Phase | Phase 4 |
| Study type | Interventional; randomized, parallel, masking: none, treatment |
| Enrollment | 164 (Estimated) |
| Sponsor | Amsterdam UMC (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 |
| Conditions | Empyema, Pleural, Pleural Infections |
| Interventions | VATS group, IET (Procedure, drug) |
| Dates | start 2026-10-01 (estimated), primary completion 2028-10-01 (estimated), completion 2029-10-01 (estimated), first posted 2026-10-21, last updated 2026-10-21 |
Related Papers Related Patents Related Grants Related Experts
All trials for Empyema, Pleural All trials for Pleural Infections All trials of VATS group All trials of IET
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).
| Arm | Type | Interventions | Description |
|---|---|---|---|
| VATS / surgical group | Experimental | Procedure: VATS group | 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. |
| Intrapleural Enzymatic Therapy (IET) | Active comparator | Drug: IET | 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. |
Sex: All, ages: 18 Years to any
Inclusion Criteria: * 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. Exclusion Criteria: * 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).