Testing whether a commonly used drug to treat Diabetes can reduce injury to the lung following heart surgery and in critical illness.
| ISRCTN | ISRCTN13139487 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13139487 |
| Integrated Research Application System (IRAS) | 1011434 |
| Protocol serial number | 24030KOS-UC |
| Sponsor | Belfast Health and Social Care Trust |
| Funder | HSC Research and Development |
- Submission date
- 14/10/2025
- Registration date
- 24/12/2025
- Last edited
- 24/12/2025
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Respiratory
Plain English summary of protocol
Background and study aims
Acute respiratory distress syndrome (ARDS) is a common condition in critically ill patients, in which the lung lining becomes damaged by white blood cells and the lungs fill with fluid, causing difficulty breathing and a need for breathing support on a ventilator. There is no cure for ARDS despite decades of research.
Metformin is a drug that is commonly used to treat diabetes. Researchers have found that metformin reduces inflammation by several different mechanisms. Excitingly, many of these mechanisms are implicated in how inflammation causes damage to the lung in ARDS. This raises the possibility that metformin might be useful in treating ARDS, and indeed in several animal models it appears to be effective. We now want to test metformin in human models of ARDS. If it is effective in these then we could progress rapidly to a clinical trial in patients who have ARDS or who are at risk of developing it. Patients undergoing coronary artery bypass grafting (CABG) experience mild lung inflammation during their surgery. We can find evidence in their blood of mild damage to the lung lining and mild inflammation, mimicking the types of changes we see in ARDS, but the inflammation in patients undergoing bypass is mild and transient.
The information from this study will help us really understand the therapeutic potential of metformin and ensure we designed the best possible clinical trials to test it in patients with ARDS.
Who can participate?
Adult patients ≥18 years of age undergoing elective coronary artery bypass graft surgery using cardiopulmonary bypass.
What does the study involve?
We will treat patients undergoing CABG with metformin and measure whether these markers of inflammation and lung injury are reduced in the group given metformin compared to a group who are undergoing standard care for their CABG procedure.
What are the possible benefits and risks of participating?
Benefits:
Not provided at time of registration
Risks:
Potential Risk:
Metformin is a marketed for use in type II diabetes at the same doses as used for this study. The summary of product characteristics (SPC) lists all known side effects of the medication.
The SPC states common side effects to be decreased appetite, abdominal pain, diarrhoea, gastrointestinal disorder, nausea, vomiting and altered taste. Gastrointestinal side effects are listed as the most frequent side effects and usually resolve spontaneously. Metformin cannot be used in patients with impaired kidneys due to risk of lactic acidosis (a significant a potentially dangerous change in the blood)
Mitigation Strategy:
Metfomin will be introduced gradually and using a regime similar to those seen to work in other trials. A modified released preparation will be used which is better tolerated.
Those with lactic acidosis or B12 deficiency will be excluded as well as those with pre-existing kidney impairment.
All trial patients will be advised of the possibility of all potential side effects and how to report them.
Potential Risk:
It had been suggested in the past that metformin increased the risk of lactic acidosis.
Large studies have demonstrated that the risk of lactic acidosis is no higher in those taking metformin as compared to those not taking metformin.
Mitigation strategy:
A baseline lactate will be taken and those with a history of lactic acidosis will be excluded. Furthermore, those with pre-existing kidney impairment will be excluded. In addition, the serum lactate will be followed closely as a safety outcome
Potential Risk:
A listed side effect of metformin within the SPC is B12 deficiency.
Mitigation Strategy:
Those with vitamin B12 deficiency will be excluded.
Potential Risk:
The majority of the clinical procedures will be undertaken as per normal clinical care. Most blood tests will be taken at the same time with routine blood tests procedure to reduce need for further blood sampling.
Blood sampling carries a very low risk of introducing infection and repeated blood draws can, in theory, contribute to anaemia. Blood sampling can also be painful.
A biopsy of pectoral muscle will be taken from the patient on entry to the chest.
Mitigation Strategy:
Taking blood for research alongside routine clinical blood tests will reduce the risk of the need for further blood draws. Where this is not possible for timed blood draws post-operatively, the blood will be taken from the existing lines which is a commonly undertaken procedure post cardiac surgery.
The muscle biopsy will be taken from pectoralis major through the sternotomy incision and it would be standard practice to encounter these muscles during this surgery. A surgical biopsy will not affect function or add risk to the procedure.
Potential Risk:
Consent not being recorded properly prior to study entry.
Site staff taking consent are not adequately trained or delegated this task.
Mitigation Strategy:
No patient will be recruited unless informed consent has been achieved. The study will be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki. The Chief Investigator (CI) is responsible for ensuring that informed consent for trial participation is given by each patient or a legal representative.
The person taking informed consent must be trained, suitably qualified and experienced. Appropriate signatures and dates must be obtained on the informed consent documentation prior to collection of trial data and randomisation. If no consent is given a patient cannot be randomised into the trial.
Potential Risk:
Data breaches of sensitive information can cause significant harm to patients.
Mitgation Strategy:
Patient confidentiality will be maintained at every stage in compliance with the General Data Protection Regulations (GDPR) & the UK Data Protection Act 2018. Patient identification will be through their unique study number allocated at the time of recruitment to the trial.
Potential Risk:
Failure to act on a participant’s request to withdraw from the study.
Patient does not feel able withdraw from the study as procedures to do so are not made clear.
Mitigation Strategy:
Patients can withdraw their consent to the trial at any time without giving a reason. This will be made clear in the participant information. Should a patient elect to withdraw from the study the researcher will discuss what information remains on the database and what is removed.
Potential Risk:
Staff or participants coming into contact with violent patients.
Mitigation Strategy:
Patients can develop delirium (confusion) after surgery and can behave out of character. This is commonly dealt with in the post-operative patient. They will be treated per standard clinical practice and therefore harm should be no higher than in standard care.
Where is the study run from?
Belfast Health and Social Care Trust (UK)
When is the study starting and how long is it expected to run for?
October 2025 to August 2029
Who is funding the study?
HSC Research and Development (UK)
Who is the main contact?
Jonathan Strickland, jstrickland01@qub.ac.uk
Katie O'Sullivan, katie.osullivan@belfasttrust.hscni.net
Contact information
Public, Scientific
Wellcome Wolfson Institute for Experimental Medicine, 97 Lisburn Road
Belfast
BT9 7BL
United Kingdom
| Phone | +44(0)7742132034 |
|---|---|
| jstrickland01@qub.ac.uk |
Principal investigator
Department of Cardiac Surgery, Royal Victoria Hospital, 274 Grosvenor Road
Belfast
BT12 6BA
United Kingdom
| Phone | +44 28 96156442 |
|---|---|
| katie.osullivan@belfasttrust.hscni.net |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Interventional randomized controlled trial |
| Secondary study design | Randomised controlled trial |
| Scientific title | Metformin to reduce pulmonary INjury and systemic Inflammation after Coronary Artery Bypass surgery? (MINICAB) |
| Study acronym | MINICAB |
| Study objectives | Primary objective: Can metformin, a commonly used medication in the treatment of diabetes, reduce blood markers of lung injury in patients undergoing coronary artery bypass grafting operations? Secondary objectives: 1. Can metformin, a commonly used medication in the treatment of diabetes, reduce blood markers of inflammation in the patients undergoing coronary artery bypass grafting surgery? 2. Can metformin, a commonly used medication in the treatment of diabetes, improve clinical outcomes following coronary artery bypass grafting surgery? 3. To evaluate how metformin works and how it might reduce lung injury and inflammation if it does have this effect. |
| Ethics approval(s) |
Not yet submitted |
| Health condition(s) or problem(s) studied | Acute Respiratory Distress Syndrome, post-operative coronary artery bypass graft patients |
| Intervention | Patients will be randomised 1:1 to either a standard care arm or treatment (metformin arm) using the sealed envelope platform. In the treatment arm of the trial, patients will receive a total of 14 days of modified release metformin with the final dose on the morning of surgery. For the first 7 days of this course patients will receive 500mg Modified Release Metformin twice daily. The subsequent 7 days of therapy will consist of 1g Modified Release Metformin twice daily. In the standard care arm the patient will receive their no change to the standard surgical workup undertaken at the trial site. Participants and clinicians involved in the patient care will be unblinded to the arm allocation. Laboratory staff undertaking the analysis will be blinded to allocation. Patients will be followed up for 30 days to for clinical outcomes. |
| Intervention type | Drug |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Metformin |
| Primary outcome measure(s) |
Plasma RAGE measured using ELISA from baseline to immediately post cardiopulmonary bypass (RAGEimmediately post bypass – RAGEimmediately pre bypass) |
| Key secondary outcome measure(s) |
At baseline and post-operative timepoints unless noted: |
| Completion date | 01/08/2029 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 110 Years |
| Sex | All |
| Target sample size at registration | 56 |
| Key inclusion criteria | Adult patients ≥18 years of age undergoing elective coronary artery bypass graft surgery using cardiopulmonary bypass. |
| Key exclusion criteria | 1. Age < 18 years 2. Patients with surgery planned within 14 days who would therefore be unable to take full course of metformin 3. Pre-existing diabetes mellitus (DM) requiring therapy 4. Participation in a clinical trial of an IMP within 30 days 5. Untreated vitamin B12 deficiency 6. eGFR<60ml/min or history of chronic kidney disease 7. Chronic hepatic disease - defined by ALT or AST >3x upper limit of normal 8. Patients with known mitochondrial disorders 9. Inability to take oral medication pre-operatively 10. Known hypersensitivity or intolerance to the study medication 11. Lack of capacity to consent to trial |
| Date of first enrolment | 09/02/2026 |
| Date of final enrolment | 01/08/2029 |
Locations
Countries of recruitment
- United Kingdom
Study participating centre
NO COUNTRY SPECIFIED, assuming England
-
England
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| IPD sharing plan |
Editorial Notes
24/12/2025: ISRCTN received notification of combined HRA/MHRA approval for this trial on 24/12/2025.
14/10/2025: Trial's existence confirmed by NHS HRA.
