Sugammadex for prevention of postoperative pulmonary complications

Plain English Summary

Background and study aims
The aim is to conduct a large clinical trial comparing two drugs used to prevent lung complications and improve recovery from general anaesthesia in patients undergoing major surgery. General anaesthesia for major surgery requires specialised drugs which temporarily paralyse patients' muscles, called neuromuscular blocking agents (NMBAs). At the end of surgery, the NMBA-induced muscle paralysis is reversed with another drug. Despite careful monitoring, incomplete reversal is common, impacting breathing patterns and predisposing to lung complications such as pneumonia. These complications are common, delay patient recovery and increase the risk of death and long-term health problems. Anaesthetists choose between two drugs to reverse muscle paralysis, neostigmine or a newer drug, sugammadex, which reverses paralysis faster and may help to prevent lung complications after surgery. However, this benefit has not yet been proven and must be weighed against two problems with sugammadex. Firstly, it is more expensive than neostigmine, doubling the drug costs of a general anaesthetic. Secondly, there is concern that allergic reactions may become more common over time with widespread use, although these are extremely rare at present.

Who can participate?
Patients aged 50 years and over undergoing major chest or abdominal surgery

What does the study involve?
Each patient who agrees to participate will be randomly allocated to receive either sugammadex or neostigmine for NMBA reversal after surgery. The researchers will follow patients up to find out if using one drug results in faster recovery or lower risk of death than the other. In a subgroup of patients, the researchers will test to find out whether there are any signs that an allergy to sugammadex has developed and could be a problem in a second operation. This will help them to understand the risks and benefits of each drug.

What are the possible benefits and risks of participating?
Participants will be exposed to one of two drugs to reverse neuromuscular paralysing drugs at the end of surgery. Both drugs are in widespread use in the NHS for this indication, with the decision typically determined by individual anaesthetist preference, and participants would be receiving one or other drug anyway. There is therefore no additional risk to the patient from the intervention.
The researchers have worked with patient representatives to minimise the burden on participants. Apart from the trial intervention, they aim to keep all other aspects of treatment unchanged from usual care. The researchers will collect only the minimum data required for the study and have outlined elsewhere how this will be kept confidential. They will offer participants a range of contact options for follow-up (e.g. email/telephone/post) in order to minimise the inconvenience involved.
The burden to participants in the allergic sensitisation substudy is greater, as they have a blood sample performed at baseline, and are asked to attend a clinic at 6 weeks to 6 months following surgery for a repeat blood sample, and a skin test if deemed appropriate by an allergy expert. Researchers will be requested, where possible, to take the baseline blood sample from an existing indwelling line (e.g. arterial or central venous line) while the patient is under anaesthesia to minimise any pain or discomfort. The amount of blood being taken (10 ml) is not clinically significant and no adverse effects are anticipated. The blood sample at the follow-up clinic will require venepuncture, but since it will be done by experienced staff and only 10 ml is required, this will be kept to a minimum. The skin test lasts for about 2 hours and involves injections of different concentrations of sugammadex into the skin using very fine needles. Redness, itch and pain are possible, but these are typically minimal and transient and can be treated with antihistamines and paracetamol if required. Patients participating in the allergic sensitisation substudy will be compensated for their time and any transport costs in keeping with NIHR guidance.
In patients undertaking the allergic sensitisation substudy, there is a very small risk of an allergic reaction to the skin test. While this risk is miniscule, it will be mitigated by the test being carried out under the supervision of an allergy expert who is trained in the management of allergic reactions, in a closely monitored environment with all necessary equipment and drugs available to treat an allergic reaction if it were to occur.

Where is the study run from?
University of Warwick (UK)

When is the study starting and how long is it expected to run for?
September 2022 to November 2026

Who is funding the study?
Health Technology Assessment Programme (UK)

Who is the main contact?
SINFONIA@warwick.ac.uk

Study website

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• England
• Northern Ireland
• Scotland
• United Kingdom
• Wales

Study participating centres

Sponsor information

Belfast Health and Social Care Trust
Hospital/treatment centre

c/o Alison Murphy
A Floor
Belfast City Hospital
Lisburn Road
Belfast
BT9 7AB
Northern Ireland
United Kingdom

Phone	+44 (0)2476 150963
Email	Alison.Murphy@belfasttrust.hscni.net
"ROR"	https://ror.org/02tdmfk69

Funders

Funder type

Government

Results and Publications

Study outputs

Additional files

ISRCTN15109717_PROTOCOL_V3.0_18Oct23.pdf

ISRCTN15109717_PROTOCOL_V4.0_02Oct24.pdf

Editorial Notes

04/04/2025: The following changes were made to the study record:
1. Protocol uploaded.
2. The interventions were updated.
3. Bronglais General Hospital, Conquest Hospital, Craigavon Area Hospital, University Hospitals Plymouth NHS Trust, East Surrey Hospital, Eastbourne District General Hospital, Forth Valley Royal Hospital, Good Hope Hospital, Heartlands Hospital, Hinchingbrooke Hospital, Liverpool Women's Hospital Cdc, Liverpool Womens Hospital, Manchester Royal Infirmary, Newham General Hospital, Norfolk & Norwich University Hospital, North Manchester General Hospital, Peterborough City Hospital, Pinderfields Hospital, Raigmore Hospital, Rotherham General Hospital, Royal Berkshire Hospital, Royal Berkshire Hospital, Royal Infirmary of Edinburgh at Little France, Royal Liverpool University Hospital NHS Trust, Royal Liverpool University Hospital, The Royal Oldham Hospital,
Scarborough General Hospital, Solihull Hospital, Sunderland Royal Hospital, University Hospital Hairmyres, Ysbyty Maelor Wrexham, Wythenshawe Hospital, and York Hospital were added to the study participating centres.
05/03/2024: Protocol uploaded, contact details updated.
21/02/2023: The recruitment start date
16/01/2023: Internal review.
21/12/2022: ISRCTN received notification of combined HRA/MHRA approval for this trial on 21/12/2022
22/09/2022: Trial's existence confirmed by the HRA.