Investigating the clinical and cost-effectiveness of two different drugs (amiodarone and beta blockers) to treat patients with new-onset atrial fibrillation whilst in the intensive care unit
| ISRCTN | ISRCTN59775011 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN59775011 |
| IRAS number | 1007930 |
| Secondary identifying numbers | RG_22-153, IRAS 1007930, CPMS 57843 |
- Submission date
- 14/09/2023
- Registration date
- 15/09/2023
- Last edited
- 10/05/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Circulatory System
Plain English Summary
Background and study aims
Each year about 10% of patients who are being treated in an ICU will develop an irregular heartbeat which they did not have previously, called new-onset atrial fibrillation (NOAF). We do not fully understand what causes NOAF in these patients but believe that it may be the result of a number of factors including:
1. Normal body reactions to infection and injury
2. Altered levels of electrolytes (salts) in a patient’s blood
3. The drugs used to support a patient’s blood pressure
4. Certain commonly used ICU procedures
Some of the studies to look at the risks associated with AF suggest that patients who develop NOAF whilst in the ICU seem to be at higher risk of complications such as heart attack and stroke, which means that they need to spend a longer time in hospital. Some patients who develop NOAF may also end up in permanent AF and require lifelong treatment. We need to do a trial because we do not have a clear understanding of the best way to treat these patients.
Who can participate?
Patients aged 16 years and over in an adult ICU who have developed NOAF
What does the study involve?
Participants will be randomly allocated to receive either amiodarone or beta-blockade. The choice of dose (and in the case of beta-blockade, the type) rests with the clinical team at site. Participants will be treated with the allocated intervention until sinus rhythm has been maintained for 24 hours. Clinicians should then consider stopping the intervention according to local practice. Both interventions can be administered by infusion/injection or orally.
Information will be collected from medical notes including the results of tests that are done as part of usual care. A researcher will monitor the patient's progress for 90 days from when they first joined the study and will collect information on:
1. The illness and treatment during their stay in ICU
2. The date the patient is discharged from ICU
3. The date the patient is discharged from hospital
4. How the patient feels around 60 days later (30-minute telephone call if discharged)
5. How the patient feels around 90 days later (30-minute telephone call if discharged)
What are the possible benefits and risks of participating?
While there is no direct benefit or financial incentives for patients that take part in this trial, the information provided by the trial may help in the long-term, to improve and shape future care for ICU patients who develop NOAF.
Where is the study run from?
The Birmingham Clinical Trials Unit (BCTU) coordinates the study at the University of Birmingham (UK)
When is the study starting and how long is it expected to run for?
October 2022 to December 2026
Who is funding the study?
The National Institute for Health and Care Research, Health Technology Assessment (UK)
Who is the main contact?
abbrupt@trials.bham.ac.uk
Contact information
Scientific
Birmingham Clinical Trials Unit
Birmingham
B15 2TT
United Kingdom
| Phone | +44 121 414 7943 |
|---|---|
| abbrupt@trials.bham.ac.uk |
Principal Investigator
Queen Elizabeth Hospital Birmingham
Mindelsohn Way
Edgbaston
Birmingham
B15 2GW
United Kingdom
| Phone | +44 7932 687308 |
|---|---|
| tony.whitehouse@uhb.nhs.uk |
Study information
| Study design | Multi-centre interventional randomized controlled open-label trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Quality of life, Treatment, Efficacy |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet. |
| Scientific title | A randomised controlled trial to investigate the clinical and cost effectiveness of Amiodarone vs Beta Blockade for new-onset atrial fibRillation in icU - a Pragmatic sTudy (ABBRUPT) |
| Study acronym | ABBRUPT |
| Study hypothesis | The ABBRUPT trial will assess the clinical and cost-effectiveness of two commonly used treatments for new-onset atrial fibrillation (NOAF) in patients in ICU to establish which management of AF is best to avoid harm and achieve optimal outcomes. |
| Ethics approval(s) |
Approved 20/10/2023, South Central - Oxford C (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; None provided; oxfordc.rec@hra.nhs.uk), ref: 23/SC/0334 |
| Condition | New onset atrial fibrillation (NOAF) |
| Intervention | Patients will be randomised following confirmation of eligibility by a medically qualified doctor. They will be randomised to receive either amiodarone or beta-blockade. The choice of dose (and in the case of beta-blockade, the type) rests with the clinical team at site. Patients randomised to amiodarone will receive a loading dose (usually 300 mg over 1 hour) followed by a continuous infusion of (usually) between 300-1200 mg (usually 900 mg) per day with the treating clinician choosing the route of administration and duration. For those patients randomised to the control group, clinicians will be given the choice of beta-blocker: bisoprolol, metoprolol, esmolol, propranolol, atenolol, labetalol, carvedilol, and landiolol. The beta-blocker choice should reflect local availability and familiarity. They may be administered enterally or intravenously; dosing should be according to local practice. Patients will be treated with the allocated intervention until sinus rhythm has been maintained for 24 hours. Clinicians should then consider stopping the intervention according to local practice. All participants will be followed up for 90 days from randomisation. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacoeconomic |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Amiodarone, atenolol, bisoprolol, carvedilol, metoprolol tartrate, propranolol, Betaloc [metoprolol tartrate], esmolol, labetalol, Rapibloc [landiolol hydrochloride] |
| Primary outcome measure | 90 day mortality measured using patient records |
| Secondary outcome measures | 1. ICU and hospital mortality measured up to day 90 using patient's medical notes 2. Rates of cardiovascular events including stroke, myocardial infarction or thromboembolism up to 90 days using patient's medical notes 3. Rate of established AF by the end of ICU stay/death/day 90 by using patient's medical notes 4. Number of episodes of bradycardia up to day 90 by using patient's medical notes 5. Number of bradycardia and bradycardic arrhythmias with haemodynamic compromise requiring intervention measured up to day 90 by using patient's medical notes 6. Number of significant hypotension episodes requiring intervention up to day 90 by using the patient's medical notes 7. Heart block measured up to day 90 by using patient's medical notes 8. Arrhythmia with haemodynamic compromise requiring intervention including DC cardioversion up to day 90 by using patient's medical notes 9. Cost-effectiveness of the interventions measured up to day 90 by using patient's medical notes 10. Healthcare resource use including ICU and hospital length of stay measured up to day 90 by using patient's medical notes |
| Overall study start date | 01/10/2022 |
| Overall study end date | 31/12/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 16 Years |
| Sex | Both |
| Target number of participants | 2,560 |
| Participant inclusion criteria | 1. Patients in an adult ICU (age ≥16 years) 2. Onset of NOAF during the acute illness (A&E, deterioration on ward, after surgery) having previously been in sinus rhythm and not known to previously have had AF. 3. A minimum duration of AF of at least 30 minutes 4. Usual electrolyte management with potassium and magnesium according to site practice 5. A clinical indication to treat NOAF as determined by the attending clinician |
| Participant exclusion criteria | 1. Patients in receipt of amiodarone or a beta-blocker in the previous 24 hours 2. Patients receiving current concomitant medication with treatments that are contraindicated with the intervention/comparator medications 3. Patients with a serum potassium of <4 mmol L-1 4. Patients with a serum magnesium of <1.0 mmol L-1 5. Patients having undergone cardiac surgery during the current hospital admission, defined as any surgery including stent procedures such as percutaneous coronary interventions or other angioplasty procedures done on the heart muscle, valves or thoracic arteries including the thoracic part of the aorta 6. Patients with Thyrotoxicosis 7. Patients where there is a plan for withdrawal of life support therapy within 24 hours 8. Patients who have had other thoracic surgery that ingresses the thorax 9. Patients with any other known contraindication or known sensitivity to beta-blockers or amiodarone 10. Patients with a known pregnancy or patients currently known to be breastfeeding 11. Patients with any known previous documented history of AF, whether permanent, persistent or paroxysmal |
| Recruitment start date | 08/05/2024 |
| Recruitment end date | 30/06/2026 |
Locations
Countries of recruitment
- England
- Northern Ireland
- Scotland
- United Kingdom
- Wales
Study participating centres
Redhill
RH1 5RH
United Kingdom
Lincoln
LN2 5QY
United Kingdom
Pond Street
London
NW3 2QG
United Kingdom
Brighton
BN2 5BE
United Kingdom
Tooting
London
SW17 0QT
United Kingdom
Taunton
TA1 5DA
United Kingdom
Pinderfields General Hospital
Aberford Road
Wakefield
WF1 4EE
United Kingdom
Sunderland
SR4 7TP
United Kingdom
Watford
WD18 0HB
United Kingdom
Sponsor information
University/education
Aston Webb Building, Block B, Room 106
Birmingham
B15 2TT
England
United Kingdom
| Phone | +44 7814650003 |
|---|---|
| researchgovernance@contacts.bham.ac.uk | |
| Website | http://www.birmingham.ac.uk/index.aspx |
"ROR" |
https://ror.org/03angcq70 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | On completion of the trial, the data will be analysed, and a Final Study Report prepared. The final report will be published in a time defined by the contract between the Sponsor (BCTU) and the Funder (HTA). Outputs from this trial will be submitted for publication in peer reviewed journals and the findings of the trial will be made public. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be available upon request from the BCTU Data Sharing Committee following a formal Data Sharing Agreement (if applicable) email: abbrupt@trials.bham.ac.uk |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 1.0 | 11/10/2023 | 10/05/2024 | No | No |
Additional files
Editorial Notes
10/05/2024: Protocol uploaded. Sunderland Royal Hospital and Watford General Hospital were added to the study participating centres.
17/04/2024: The recruitment start date was changed from 01/04/2024 to 08/05/2024.
21/11/2023: Ethics approval added.
16/10/2023: The recruitment start date was changed from 01/10/2023 to 01/04/2024.
04/10/2023: Internal review.
14/09/2023: Trial's existence confirmed by NHS HRA.
