VATS versus Intrapleural Alteplase/Dornase Alfa Enzymatic Therapy for Parapneumonic Pleural Infection (Empyema) in Patients Unresponsive to Antibiotics and Chest Tube Drainage

The primary objective is to determine which treatment modality—video‑assisted thoracoscopic surgery (VATS) or intrapleural enzymatic therapy—produces a shorter length of hospital stay in patients with parapneumonic pleural infection (pleural empyema) unresponsive to initial antibiotics and chest‑tube drainage. Secondary objectives include:

• Assessment of the comparative impact of each modality on patient‑reported outcome measures such as pain intensity and return to daily activities or work.
• Evaluation of the relative safety and overall efficacy of the treatment options.
• Analysis of the cost‑effectiveness associated with each therapeutic approach.

The sponsor did not provide information on the total number of participants. The trial enrolled adult patients (≥ 18 years) of both sexes who were diagnosed with pneumonia and suspected parapneumonic pleural infection, confirmed by pleural fluid characteristics (purulent, positive Gram stain or culture, pH < 7.2, glucose < 2 mmol/L) and radiological findings. Eligible individuals were required to be fit for surgery, meaning they could tolerate one‑lung ventilation, and to have demonstrated failure of standard care (chest tube and antibiotics) within 24 hours of tube insertion as judged by radiology, inflammatory markers, or clinical status. Participants also needed to be able to provide informed consent. General health status was therefore limited to hospitalized patients with ongoing pleural infection unresponsive to initial therapy. No specific lifestyle criteria were reported.

The VIETS trial is a low‑intervention, controlled comparative study evaluating video‑assisted thoracoscopic surgery (VATS) versus intrapleural enzymatic therapy with alteplase and dornase alfa in adults with parapneumonic pleural infection unresponsive to initial antibiotics and chest‑tube drainage. Eligible participants (≥18 years, confirmed pleural infection, fit for single‑lung ventilation, and failure of standard care within 24 h) undergo a screening visit to assess inclusion criteria and obtain informed consent. At the baseline visit, participants are allocated to one of the two treatment arms and receive the assigned intervention; subsequent in‑hospital visits monitor chest‑tube duration, pain, laboratory parameters, and adverse events. Follow‑up assessments are performed at discharge, on day 30, and at the end‑of‑study visit to capture primary (length of hospital stay) and secondary outcomes, including re‑intervention rates, morbidity, mortality, patient‑reported outcomes, and economic measures. Participant involvement lasts for the hospitalization period plus a 30‑day post‑treatment follow‑up, with the overall trial scheduled from July 2026 to June 2029. Early termination may occur if a participant withdraws consent, experiences a serious adverse event, or deviates significantly from the protocol, prompting discontinuation from the study.

The investigational arm includes alteplase supplied as Actilyse 20 mg, a powder and solvent for preparation of a solution for injection/infusion. The product is administered via the intrapleural route as a 20 mg dose in solution form. Dosing is performed according to the study protocol, typically as a single administration per treatment cycle.

The second investigational agent is dornase alfa provided as Pulmozyme 2500 E/2.5 ml, a nebuliser solution. It is delivered intrapleurally at a dose of 10 mg per administration. The medication is prepared and instilled into the pleural space in accordance with the protocol, with each dose given once per treatment cycle.

All participants receive standard-of-care management for parapneumonic pleural infection, which includes systemic antibiotic therapy and chest‑tube drainage as clinically indicated.

Drug administration is documented in the trial eCRF, and study personnel verify compliance by confirming infusion times, volume administered, and any adverse events. Monitoring includes regular assessment of dosing records and observation of the intrapleural instillation procedure to ensure protocol adherence.

Efficacy will be assessed primarily by measuring Length of hospital stay (LOS) during the first 30 days following randomization. Secondary efficacy assessments will include treatment‑related parameters such as duration of chest tube drainage, delayed discharge days, rates of re‑intervention and re‑admission, morbidity and mortality, and the type and duration of antibiotic and analgesic therapy. Patient‑reported outcomes will be captured for pain, health‑related quality of life, limitations in daily activities, and return to work. An economic evaluation will quantify healthcare costs, patient costs, productivity loss, and health‑related quality of life. All endpoints will be derived from clinical records and standardized patient questionnaires as defined in the trial protocol.