Plain English Summary
Background and study aims
Major operations in the stomach or chest provide life-saving operations for people with cancer or a heart condition. As with all major surgery, there is a chance of developing complications after the operation. The Inspire study is concerned with lung complications, including pneumonia. Lung complications after surgery are common, affecting on average one in ten patients, although it depends on the current health of the person and the type of surgery they are having. Lung complications have a long term effect, and can reduce life expectancy for up to ten years after the operation. Poor health due to lung complications also increases healthcare costs. Consequently, trying to prevent lung complications is important for both patients and the NHS.
The study aims to investigate whether breathing training reduces lung complications in patients who, because of their health or the operation they are having, have a higher than average risk of developing lung complications after surgery. Some studies have shown that training for as little as two weeks before a major operation halves the risk of lung complications. The benefits of this training, however, remain uncertain as previous studies recruited too few patients and many were not done well.
Who can participate?
Adult patients having operations in the chest or stomach under general anaesthesia.
What does the study involve?
The Inspire study is investigating whether a series of daily breathing exercises that aim to improve the strength and endurance of the muscles in the chest can help to reduce the chances of getting a lung complication after surgery. The exercises involve using a hand-held device held up to the mouth, through which the patient will breathe in and out. Training takes approximately 15 minutes twice a day and can be performed at home whilst sitting down.
To try to make sure the groups are the same to start with, each patient is put into a group randomly. Each person taking part will have an equal chance of being in either group. If a patient takes part in the research neither they, nor the surgeon, nor the research team will be able to choose which breathing technique they are given.
Group 1: Breathing training with the hand-held device with resistance/difficulty: Patients will be taught how to use the device and perform the exercises and instructed to do the exercises twice a day (30 breaths each time, which will take approximately 15 minutes) for a minimum of 2 weeks. If the patients have a longer wait for surgery or their surgery date is rescheduled then they can continue doing the exercises until the day before their operation.
Group 2: Breathing training with the hand-held device with less resistance/difficulty: as above.
Group 3: Breathing exercises without the hand-held device: Patients will be given an instruction leaflet with a series of deep breathing exercises but will otherwise have no additional breathing training before surgery.
What are the possible benefits and risks of participating?
The researchers cannot promise that the study will help participants, but they anticipate that participants who perform breathing exercises before surgery will have fewer lung complications and recover from surgery more quickly. The results from this study may help improve the management of some complications that could develop after surgery, for other people having operations in the future.
There are no known risks associated with performing breathing exercises. However, if participants have problems operating the breathing device or experience untoward events the local research team will provide contact details on joining the study.
There should also be no risks associated with participating in the information study, as this only involves audio-recording conversations participants have with hospital staff and researchers. Most people find these conversations helpful but some can find it upsetting. If this happens, participants will be able to stop the appointment or interview at any time, without giving a reason.
Where is the study run from?
1. Southampton General Hospital, UK
2. Royal Surrey County Hospital, UK
3. Royal Hallamshire Hospital, UK
4. Nottingham NHS Treatment Centre, UK
5. Hull Royal Infirmary, UK
When is the study starting and how long is it expected to run for?
November 2019 to September 2021
Who is funding the study?
National Institute for Health Research Health Technology Assessment Programme, UK
Who is the main contact?
1. Dawn Phillips (public)
inspire-study@bristol.ac.uk
2. Dr Maria Pufulete
maria.pufulete@bristol.ac.uk
Trial website
http://cteu.bris.ac.uk/our-studies/?trialType=General-surgery#5205
Contact information
Type
Public
Primary contact
Miss Dawn Phillips
ORCID ID
http://orcid.org/0000-0002-1322-472X
Contact details
Bristol Trials Unit (CTEU)
University of Bristol
Zone A719 Queens Building
Bristol Royal Infirmary
Bristol
BS2 8HW
United Kingdom
+44 (0)117 3423564
inspire-study@bristol.ac.uk
Type
Scientific
Additional contact
Dr Maria Pufulete
ORCID ID
http://orcid.org/0000-0002-1775-1949
Contact details
Bristol Trials Unit (CTEU)
University of Bristol
Zone A719 Queens Building
Bristol Royal Infirmary
Bristol
BS2 8HW
United Kingdom
+44 (0)117 342 4195
maria.pufulete@bristol.ac.uk
Additional identifiers
EudraCT number
Nil known
ClinicalTrials.gov number
Nil known
Protocol/serial number
6296, HTA 16/140/07, CPMS 39337, IRAS 250345
Study information
Scientific title
Effectiveness and cost-effectiveness of INSPIRatory musclE training (IMT) for reducing postoperative pulmonary complications (PPC): a sham-controlled randomised controlled trial (RCT): INSPIRE
Acronym
INSPIRE
Study hypothesis
Inspiratory muscle training (IMT) performed twice per day for a minimum of 2 weeks before an operation reduces the risk of lung complications in patients at high risk of having lung complications.
Ethics approval
Approved 16/05/2019, London - Bloomsbury Research Ethics Committee (Health Research Authority, Skipton House, 80 London Road, London, SE1 6LH; +44 (0)207 104 8063; nrescommittee.london-bloomsbury@nhs.net), ref: 19/LO/0546
Study design
Pragmatic parallel three-group multi-center interventional randomized controlled trial (with an internal pilot)
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Condition
Patients undergoing major surgery who are at high risk of developing lung complications after surgery
Intervention
INSPIRE is a pragmatic parallel, 3 group multi-center RCT (with an internal pilot) with high resistance IMT, low resistance IMT and usual care interventions. During the internal pilot we will also conduct a study within a trial (SWAT).
The pilot study will check whether participants need more than one session of training to be able to use the breathing device correctly. There will be two groups as follows:
Group A: Extra one-off hospital visit one week after being randomised to Group 1 to receive further training on using the breathing device. Group B: No additional hospital visits or training.
Results will be analysed at the end of the pilot study, and if it is found that the additional training improves device use we may include the extra training in the larger study.
The main study consists of patients being recruited in a 2:1:1 ratio into one of the following three groups:
1. High resistance inspiratory muscle training (IMT) training at 50% of their maximal inspiratory pressure (MIP)
2. Low resistance IMT (control) training at 10% of their MIP
3. Usual care arm (patients will be given a breathing exercise leaflet)
The random allocation will be stratified by hospital site and specialty.
During Phase 1 of the study patients randomised to the high resistance IMT arm will be included in a study within a trial (SWAT) and will be further randomised in a 2x2 factorial design to one of the following four groups:
1. Automatic load adjustment and an additional hospital visit
2. Automatic load adjustment and no additional hospital visit
3. Manual load adjustment and an additional hospital visit
4. Manual load adjustment and no additional hospital visit
Patients will receive appropriate training on how to use the device and on how to perform breathing exercises and will be asked to train for a minimum of 2 weeks but no longer than 8 weeks before their planned operation.
Intervention type
Behavioural
Phase
Drug names
Primary outcome measure
Incidence of any post-pulmonary complication (PPC) occurring in-hospital (before discharge) or hospital readmission for a PPC within 30 days from surgery in each of the three care groups. We will use the composite outcome proposed by the European Society of Anaesthesiology and the European Society of Intensive Care Medicine as a consensus definition for PPC. This includes respiratory failure, respiratory infection, atelectasis, pleural effusion, pneumothorax, aspiration pneumonitis and bronchospasm; there are specified diagnostic criteria for each component.
Secondary outcome measures
Measured using patient notes unless stated otherwise:
1. Incidence of each of the seven individual components of the composite primary outcome (defined using the European Society of Anaesthesiology and the European Society of Intensive Care Medicine) during the study period:
1.1. Respiratory infection (patient notes & chest x ray)
1.2. Respiratory failure
1.3. Pleural effusion (patient notes & chest x ray)
1.4. Atelectasis (patient notes & chest x ray/chest ct)
1.5. Pneumothorax (patient notes & chest x ray)
1.6. Bronchospasm
1.7. Aspiration pneumonitis (patient notes & chest x ray)
2. The requirement for postoperative ventilation (invasive ventilation; non-invasive ventilation ( including continuous positive airway pressure (CPAP) and/or pressure support (BIPAP)); or Optiflow (high flow nasal oxygen therapy)). For non-invasive ventilation and high flow nasal oxygen therapy the researchers will distinguish prophylactic use from use to treat a pulmonary complication
3. Length of ICU stay
4. Length of hospital stay (including readmissions)
5. Antibiotic prescription given during hospital stay
6. Bronchodilator prescription given during hospital stay
7. Quality of life measured using HRQoL questionnaires at baseline and day of surgery, 3 months & 6 months. A combination of the following questionnaires will be issued across the 4 timepoints: EQ-5D-DL; SF-12; Connor Davidson Resilience; Duke Activity Status Index; Hospital Anxiety And Depression Scale; Self-efficacy; Surgical Regret
8. Maximal inspiratory pressure (MIP) measured using POWERbreathe device that calculates residual volume at baseline and randomisation, additional training visit (for those patients randomised to an extra visit) and day of surgery
9. Spirometry (forced expiratory volume, FEV1 and forced vital capacity, FVC) measured using a spirometer at baseline, randomisation and day of surgery
10. Training load measured using POWERbreathe device and patient diary at baseline and day of surgery
11. Mortality
12. Resource use collected from patient notes & patient questionnaires at 3 and 6 months
13. Other complications of surgery documented using the Clavien-Dindo classification and the Comprehensive Classification Index
Overall trial start date
01/10/2018
Overall trial end date
30/09/2021
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Age ≥18
2. Elective major cardiac, thoracic and abdominal surgery (oesophageal, gastric, hepatobiliary, colorectal, gynaecological, urological, or open aortic aneurysm repair) under general anaesthesia, including both open and laparoscopic surgery
3. ARISCAT score ≥26
4. At least 14 days until planned operation date
5. Able to give informed consent
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
2500
Participant exclusion criteria
1. Emergency surgery
2. Unable to participate in the intervention (e.g. have cognitive impairment)
3. Lack capacity to consent
4. Recent cardiac, thoracic or open abdominal surgery (in previous 2 months)
5. Prisoners
6. Patients with a history of spontaneous pneumothorax (if a patient has had a traumatic pneumothorax and are fully recovered, then they can be included)
7. Eardrum perforation within 6 weeks
8. Phrenic nerve palsy
Recruitment start date
02/12/2019
Recruitment end date
30/06/2021
Locations
Countries of recruitment
United Kingdom
Trial participating centre
University Hospital Southampton NHS Foundation Trust
Southampton General Hospital
Southampton
SO16 6YD
United Kingdom
Trial participating centre
Royal Surrey County Hospital
Egerton Road
Guildford
GU2 7XX
United Kingdom
Trial participating centre
Sheffield Teaching Hospitals NHS Foundation Trust
Royal Hallamshire Hospital
Glossop Rd
Sheffield
S10 2JF
United Kingdom
Trial participating centre
Nottingham University Hospitals NHS Trust
Nottingham NHS Treatment Centre
Lister Road
Nottingham
NG7 2FT
United Kingdom
Trial participating centre
Hull University Teaching Hospitals NHS Trust
Hull Royal Infirmary
Anlaby Road
Hull
HU3 2JZ
United Kingdom
Trial participating centre
Royal Marsden Hospital
203 Fulham Rd
Chelsea
London
SW3 6JJ
United Kingdom
Trial participating centre
Northern General Hospital
Sheffield Teaching Hospitals NHS Foundation Trust
Herries Road,
Sheffield
S5 7AU
United Kingdom
Trial participating centre
Castle Hill Hospital
Hull University Teaching Hospitals NHS Trust
Castle Rd
Cottingham
Hull
HU16 5JQ
United Kingdom
Trial participating centre
Nottingham University Hospitals
Derby Road
Nottingham
NG7 2UH
United Kingdom
Sponsor information
Organisation
University Hospitals Bristol NHS Foundation Trust
Sponsor details
Research & Innovation
Bristol Royal Infirmary
Upper Maudlin Street
Bristol
BS2 8HW
United Kingdom
+44 (0)117 34 20233
research@uhbristol.nhs.uk
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Government
Funder name
Health Technology Assessment Programme
Alternative name(s)
NIHR Health Technology Assessment Programme, HTA
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
A full report will be written for the NIHR HTA and the findings will be presented at national and international conferences, and the results published in peer-reviewed journals. Several aspects of the study (e.g. the inclusion of both a low resistance IMT and usual care arms will allow the researchers to assess the efficacy of blinding such an intervention) will inform RCTs of lifestyle interventions in general and these will be reported at methodology meetings. The researchers will also link with the British Heart Foundation, Cancer Research UK, the Royal College of Anaesthetists and the James Lind Alliance Priority Setting Partnership for Anaesthesia and Perioperative Care, the UK Perioperative Medicine Clinical Trials Network, the National Institute of Academic Anaesthesia (NIAA) and NIAA Health Services Research Centre, the European Society of Anaesthesiology, and other relevant clinical studies groups (CSGs) (e.g. lung cancer CSG). They will use social networking media to disseminate and publicise the study via a website or social media streams. They will also work with PPI groups to identify how they can best publicise their findings.
Expected outputs include publication of the protocol and the results of the RCT informing clinicians and patients on the efficacy of IMT for preventing postoperative complications. The study will also provide information on the feasibility of delivering a lifestyle intervention in a pragmatic fashion to patients in the NHS setting. The health economic evaluation will provide evidence on the cost effectiveness of IMT and whether it presents value for money for the NHS. The results of the study will inform national and international guidelines on optimising the perioperative care pathway.
IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
01/03/2023
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list