Conservative Management in Primary Spontaneous Pneumothorax: a Multicenter Randomized Non-inferiority Study

Background and Rationale Primary spontaneous pneumothorax (PSP) commonly affects young, otherwise healthy individuals. Large PSP has traditionally been managed with chest tube drainage and hospital admission, which can cause pain, longer stays, and procedure-related complications. Emerging evidence and guideline trends suggest that, in clinically stable, minimally symptomatic patients, a conservative strategy (no immediate invasive procedure) may be as effective as invasive options while reducing complications and improving patient experience. However, the current evidence base remains limited, justifying a multicenter randomized trial to rigorously compare both strategies. This protocol uses the Collins method on chest radiography to estimate pneumothorax size because it correlates with CT-based estimates and is practical for routine care. Primary Objective To demonstrate the non-inferiority of conservative management compared with chest tube drainage in achieving complete lung re-expansion at 8 weeks, defined as no pleural air on chest X-ray. Secondary Objectives Between strategies, to compare: treatment-related complications (e.g., bleeding, infection, persistent air leak, tension physiology), recurrence up to 2 years, quality of life and patient satisfaction (including EQ-5D-5L), time to clinical and radiographic resolution, length of hospital stay, number of invasive procedures, days of work/disability, drainage characteristics in the invasive arm, healthcare costs, and site-level variation (e.g., hospitals with or without thoracic surgery on site). Study Design Prospective, randomized, multicenter, non-inferiority clinical trial comparing no initial intervention (conservative strategy) versus standard treatment (chest tube drainage) in large PSP with clinical stability. The trial assesses effectiveness, safety, quality of life, and cost-effectiveness. Sponsor and Sites The study is sponsored by an academic research institute. Multiple sites across Spain are currently recruiting; specific site names are not listed here. Target Population Adults with large PSP who are clinically stable and eligible for conservative management within the trial context. (Detailed inclusion/exclusion criteria are provided in the Eligibility section of the registry and are not duplicated here.) Interventions Conservative management (experimental): Initial observation in the hospital with a control chest X-ray ≥4 hours after the diagnostic film. If clinical and radiographic stability persists, discharge home with scheduled outpatient follow-up: approximately 1-week review with pre-visit chest X-ray, then every \~2 weeks until radiographic resolution (up to 8 weeks of conservative management if no earlier resolution). Rescue with chest tube if clinical deterioration or radiographic progression occurs at any point. Standard treatment (comparator): Chest tube insertion per usual care and hospital admission. Routine outpatient follow-up after discharge. Randomization and Blinding Central randomization is performed via a secure electronic system (e.g., REDCap) with concealed allocation. Given the nature of the interventions (no procedure vs. chest tube), the trial is open-label for participants and clinicians; the protocol specifies standardized follow-up procedures and quality checks to minimize assessment bias. Outcomes and Assessments Primary outcome: Complete lung re-expansion at 8 weeks on chest X-ray (no pleural air). Imaging is read by the clinical team with predefined verification procedures to support consistency. Key secondary outcomes: Complications, recurrence to 2 years, quality of life (including EQ-5D-5L), time to clinical/radiographic resolution, hospital length of stay, number of invasive procedures, days of work/disability, drainage parameters (in the invasive arm), healthcare costs, and exploratory comparisons by site type. Sample Size and Statistical Plan Planned enrollment is 436 participants (218 per group), assuming 8-week resolution rates of approximately 98% (drainage) and 97% (conservative), a non-inferiority margin of 5%, α=0.05, and β=0.20. Analyses will follow intention-to-treat and per-protocol principles (for the latter, participants randomized to conservative management who require chest tube due to progression/deterioration at the ≥4-hour assessment are analyzed within the interventional framework as specified). A mid-trial analysis is planned at \~50% enrollment with appropriate statistical safeguards. A health economic evaluation will estimate incremental costs and outcomes between strategies. Procedures and Follow-up Schedule Screening and consent at diagnosis (emergency department or inpatient setting). Randomization via the electronic system and initiation of assigned management. Conservative arm: observation and ≥4-hour repeat film; if stable, discharge with structured follow-up (≈1 week, then every \~2 weeks) including chest X-rays until resolution or 8 weeks. Chest tube arm: hospital admission with standard care and routine outpatient follow-up after discharge. Long-term follow-up for recurrence up to 2 years (clinic visits and/or phone contacts per schedule). Data Management and Quality Assurance Participating sites are trained to deliver the protocol consistently. The coordinating center conducts periodic internal audits/monitoring of enrollment, protocol adherence, data completeness, and safety reporting. Data are captured prospectively in a secure electronic database (e.g., REDCap) with role-based access, validation checks, and audit trails. Network Size and Timelines A national network is active. Assuming an average of \~1.5-2 participants per site per month and \~12 active sites, anticipated accrual is \~18-24 participants/month, yielding a \~20-24-month recruitment period (with allowances for start-up variability). Total on-study time includes follow-up for the primary endpoint at 8 weeks and recurrence monitoring to 2 years. Ethics and Safety Both strategies are accepted standards of care for stable PSP; the study does not introduce experimental procedures. Participant confidentiality follows applicable regulations (e.g., GDPR). Consent forms and linkage files are stored securely; access is limited to authorized study personnel, auditors, and regulators as required. Safety oversight includes predefined criteria for rescue intervention and adverse event reporting. Clinical Relevance If non-inferiority of conservative management is confirmed, the results could reduce invasive procedures and hospital stays, improve patient-reported outcomes, and optimize resource use in PSP-while maintaining comparable resolution rates and safety. Findings would support more selective use of chest tubes, align practice with up-to-date evidence, and incorporate patient preferences when clinically appropriate.