Effectiveness and cost-effectiveness of INSPIRatory musclE training (IMT) for reducing postoperative pulmonary complications (PPC): a sham-controlled randomised controlled trial (RCT) (INSPIRE)

Design: Pragmatic, sham controlled, randomised controlled trial (RCT) with a pilot phase (phase 1) that includes a QuinteT Recruitment Intervention (QRI) to maximise recruitment and retention. Phase 1 will determine the feasibility of recruitment from different surgical populations, adherence to the interventions, and the efficacy of an unsupervised intervention. The full RCT will evaluate the effectiveness and cost effectiveness of inspiratory muscle training (IMT) vs sham IMT or usual care. Participants will be randomised in a 2:1:1 ratio to IMT, sham IMT or usual care. Setting: Phase 1: minimum of 4 centres (Bristol, Southampton, Sheffield and Surrey). Phase 2: an additional 2 centres, minimum. Target population: Adults at high risk of PPCs undergoing elective major cardiac, thoracic or abdominal (oesophageal, gastric, hepatobiliary, colorectal, gynaecological, urological, open aneurysm repair) surgery. Inclusion criteria: Aged >=18, ARISCAT score >=26, elective major surgery, under general anaesthesia, able to give informed consent at least 2 weeks before planned surgery. Exclusion Criteria: Emergency surgery, unstable co-morbidities; inability to participate in IMT (e.g. cognitive impairment). Health technologies being assessed: (1) IMT: 30 breaths 2x/d for minimum 2 weeks (starting at 50% of individual patient MIP and progressing to achieve the highest tolerable intensity); (2) Sham IMT: as above but constant resistance (10% throughout); (3) Usual care plus written information on deep breathing exercises. Measurement of costs and outcomes: Progression criteria to full RCT: 4 sites recruiting; interventions delivered according to the protocol; adherence to interventions >=70%. Main trial outcomes: Primary: PPC composite outcome European Consensus Definition; Secondary: individual elements of the composite outcome; postoperative ventilation (invasive and non-invasive), length of intensive care unit and hospital stay; antibiotic use; health related quality of life (EuroQol-5D and SF-12, the cost and outcome data will be brought together in a cost-effectiveness model); MIP; mortality. Sample size: 2,500 participants (1250 IMT, 625 sham and 625 usual care) will provide 90% power to detect a 5% difference in the primary outcome (20% vs 15%, risk ratio 0.75) between IMT versus sham and usual care combined. We do not anticipate a difference between the sham and usual care groups and will be able to quantify a zero difference with a 95% CI of width +/-4.5%. Statistical analysis: Intention to treat analysis following CONSORT reporting guidelines. Treatment effects will be reported with 95% CIs. QuinteT Recruitment Intervention (QRI): Interviews with clinicians and patients, audio recordings of information appointments where the study is described to eligible patients. Data will be analysed using constant comparison method and Conversation Analysis. Project timetables including recruitment rate: The study will run over 42 months; 8 months set-up, 25 months recruitment (phase 1, 8 months, 4 sites, 321 patients; phase 2, 17 months, 6 sites, 2195 patients), 6 months follow-up on all participants, 6 months analysis and report. Expertise in team: The team includes patient groups, clinicians (critical care physicians, anaesthetists and surgeons), IMT experts, researchers from 2 NIHR Biomedical Research Units, a UKCRC-registered clinical trials unit, and a health economist.