Condition category
Surgery
Date applied
25/11/2019
Date assigned
20/12/2019
Last edited
13/01/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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

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

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

http://www.uhbristol.nhs.uk/research-innovation/

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

Publication citations

Additional files

Editorial Notes

13/01/2020: Added CPMS number. 20/12/2019: Trial's existence confirmed by the NIHR.