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

Abstract: 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.

Lay abstract: After major operations, some patients develop complications of the lungs, including pneumonia. These complications can be serious and may result in long stays in hospital, admission to intensive care and even death. They also prolong recovery and reduce patients’ quality of life. Lung complications after surgery have a longer term effect, increasing the risk of dying for up to ten years. Poor health due to lung complications also increases healthcare costs. Lung complications are common, affecting on average one in ten patients, with the risk for a particular individual depending current health and the type of surgery. Consequently, trying to prevent lung complications is important for patients and the NHS. Inspiratory muscle training is a package of breathing exercises to improve the strength and endurance of the muscles in the chest which control breathing. The exercises involve breathing in and out through an inexpensive, hand held device which makes breathing difficult. Training is completely safe. It takes approximately 15 minutes twice a day and can be performed at home when sitting down. Recent studies have suggested that training for as little as 2 weeks before an operation might halve the risk of lung complications. Unfortunately, the benefits of breathing training remain uncertain because the previous studies recruited too few patients and many were not done well. We propose a large study to investigate whether breathing training reduces lung complications in patients at high-risk of lung complications after major surgery. We will invite adult patients having operations in the chest or abdomen under general anaesthesia who have a high risk of lung complications to take part. We will randomly assign participants to one of three different types of treatment in the period leading up to the operation. 1. Breathing training group. Patients will be taught to do the exercises and instructed to do them twice a day (30 breaths each time) for a minimum of 2 weeks. If they have a longer wait, they can continue doing the exercises until the operation. 2. Low ‘power’ breathing training group. Patients will do the same as for the high intensity group but with the device set to a level of difficulty which will not change the strength and endurance of the breathing muscles. It is important that patients in this group believe that they are actually doing the training as intended. The aim of this group is to account for the “placebo’” effect and ensure that any reduction in lung complications in the IMT is “real”. 3. Usual care group. Patients will be given advice about the importance of deep breathing exercises but will otherwise have no additional treatment or training before surgery. The clinical team looking after patients at the time of surgery will not know which group they are in. The effect of the training will be assessed immediately before the operation by testing the strength of the respiratory muscles. We will also monitor how much training patients are able to complete. Our main aim is to compare the risk of lung complications in the three groups, to establish if breathing training is beneficial to patients. We will also compare the time patients spend in hospital, their quality of life after their operation and survival. The costs of the treatment and any cost savings caused by staying less time in hospital will also be investigated.

Research activity codes: 6.3 MEDICAL DEVICES
Health categories: GENERIC HEALTH RELEVANCE