Randomized Trial of Early Pleural Irrigation with Sodium Chloride Versus Standard Care for Complicated Pleural Infections

The primary objective is to compare the risk of treatment failure at 30 days between an early pleural irrigation strategy with saline and standard care in pleural infections. Treatment failure is defined as a composite outcome including death, the need for thoracic surgery, or additional intrapleural enzyme therapy. This outcome is clinically relevant because it assesses whether early irrigation reduces escalation of care and short-term adverse clinical course. Secondary objectives include the volume of pleural fluid drained from randomization to day 3, the incidence of serious and non-serious adverse events during trial treatment administration, intra-hospital mortality and mortality at 30 and 90 days, the rate of thoracic surgery within 30 days, the rate of intrapleural enzyme therapy within 30 days, the length of hospital stay, radiographic clearance by day 3, lung function outcomes at 90 days, and residual pain at discharge and at 90 days.

The sponsor did not provide the total number of participants. The study population included adult men and women with pleural infections. Participants were selected from patients with complicated pleural infection requiring thoracic drainage. The population was defined by clinical features such as macroscopically purulent fluid, positive Gram stain or culture for bacterial infection, loculated effusion, pH below 7.2, or marked pleural fluid abundance. An initial ultrasound evaluation was used to estimate pleural fluid abundance and detect fibrinous septation. Social security affiliation and written informed consent were required. No lifestyle considerations were provided.

EPISSOC is a randomized controlled trial comparing an early pleural irrigation strategy with saline to standard care for complicated pleural infections. Adults with complicated pleural infection requiring thoracic drainage are screened for eligibility, including initial ultrasound assessment and confirmation of informed consent. After randomization, participants receive the assigned management strategy and are followed to assess treatment failure at 30 days, defined as death, the need for thoracic surgery, or additional intrapleural enzyme therapy. Study visits include the screening visit for eligibility assessment, follow-up assessments during the study period, and an end-of-study visit at 30 days. The overall trial duration is planned from 30 June 2026 to 30 September 2029. Participant involvement is expected to last 30 days after randomization. Early termination may occur in the event of death, thoracic surgery, or the need for additional intrapleural enzyme therapy, which also constitute components of the primary endpoint.

The investigational treatment consisted of sodium chloride administered by respiratory use as pleural irrigation. The product was provided as a solution without a specified pharmaceutical form in the source data. The total dose was 3 L. Administration was performed according to the trial schedule for the early pleural irrigation strategy. Compliance monitoring was based on treatment administration as part of the study procedures.

The comparator treatment was standard of care for complicated pleural infections. The background treatments listed in the study included clindamycin phosphate 900 mg as a solution for injection/infusion by intravenous infusion, dornase alfa 2.5 mg as a nebuliser solution by inhalation, urokinase 5,000 U as a solution for injection/infusion by intravenous infusion, linezolid 1,200 mg as a solution for infusion by intravenous infusion, alteplase 90 mg as a solution for injection/infusion by intravenous use, cefepime dihydrochloride monohydrate 6 g as a solution for injection/infusion by intravenous injection or intravenous infusion, piperacillin and tazobactam 16 g as a solution for intravenous infusion, amoxicillin and clavulanic acid 6 g as a solution for injection/infusion by intravenous administration, vancomycin 2 g as a solution for infusion by intravenous use, cefotaxime 6 g as a solution for injection by intravenous administration, and metronidazole 1.5 g as a solution for infusion by intravenous infusion. These treatments were administered as background therapy in the study. Dosing schedules and adherence were handled according to the trial protocol and monitored through treatment administration.

Efficacy will be assessed by treatment failure at 30 days. Treatment failure is defined as a composite outcome including death, the need for thoracic surgery, or the requirement for additional intrapleural enzyme therapy after randomisation. Secondary efficacy assessments will include the volume of pleural fluid drained from randomization to day 3, intra-hospital mortality, 30-day mortality, 90-day mortality, the rate of thoracic surgery within 30 days, the rate of additional intrapleural enzyme therapy within 30 days, and length of hospital stay from randomization to discharge to home or transfer to a rehabilitation facility.

Safety-related events will also be recorded on day 3, including serious and non-serious adverse events such as fever, allergic reactions, bleeding, and chest tube obstruction.