A multi-centre, feasibility, cluster randomised controlled trial comparing restrictive versus liberal blood transfusion strategies in adult patients admitted with acute upper gastrointestinal bleeding.
Acute upper gastrointestinal bleeding (AUGIB) accounts for 14% of all red blood cell (RBC) transfusions in England. In 2007, a large UK national audit of AUGIB highlighted areas of variation and uncertainty in RBC transfusion practice together with signals of harm associated with more liberal use of RBCs, justifying the need for a randomised controlled trial (RCT) to answer a key area of clinical uncertainty.
TRIGGER is a pragmatic cluster randomised feasibility trial aiming to recruit adult patients admitted to hospital with all cause AUGIB. The study will take place in six UK hospitals and each hospital will be randomised to a transfusion policy; three sites will be randomised to a restrictive transfusion policy and three to a liberal transfusion policy. Both transfusion policies are used by doctors and hospitals in the UK already as part of routine care in the management of AUGIB and are within the limits of local hospital, national and international guidelines. Each cluster will agree to follow the transfusion policy for all eligible patients admitted with AUGIB for a total of 6 months at each site. Consent will be sought from an appropriate "guardian" of the cluster and individual participants for use of data collection and Day 28 telephone follow up. Given the challenges involved in early recruitment and cross-specialty care of patients, a feasibility study is essential to both justify and inform the design of a phase III trial.
First MREC 20/04/2012, ref: 12/SC/0062
Randomised interventional pilot study
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
The trial will compare two different policies for RBC transfusion, 'restrictive' and 'liberal'.
Restrictive transfusion policy: Patients in hospitals allocated to this group will receive a transfusion if their Hb level is =8 g/dL. The objective for the attending clinician is then to maintain the Hb level between 8.1-10 g/dL
Liberal transfusion policy: Patients in hospitals allocated to this group will receive a transfusion if their Hb level is =10 g/dL.
The objective for the attending cl; Follow Up Length: 1 month(s)
Primary outcome measures
1. Protocol adherence
2. Selection bias
3. Recruitment rate
4. Red cell exposure
5. Information to inform the sample size of the phase III trial
Clinical Outcomes: Further bleeding up to Day 28: Further bleeding is a composite outcome that includes persistent bleeding
Secondary outcome measures
1. Further bleeding
2. 28-day mortality
4. Ischaemic/thromboembolic events
We will also collect data to guide a Health Economic evaluation for the phase III trial.
Overall trial start date
Overall trial end date
Participant inclusion criteria
1. Adults aged = 18 years presenting with AUGIB, defined by haematemesis or melaena.
2. >20 admissions with AUGIB per month
3. >400 hospital beds
4. Availability of 24 hours endoscopy and on-site access to intensive care and surgical support
5. Institutional agreement to transfuse all eligible new admissions with AUGIB in accordance with the randomised transfusion policy
6. Male & female participants
7. Lower Age Limit 18 years
Target number of participants
UK Sample Size: 849
Participant exclusion criteria
1. Patients for whom the responsible clinician considers there is a need for immediate RBC transfusion prior to obtaining or regardless of the initial Haemoglobin (Hb) result due to severity of bleeding (these patients should be managed according to the hospital's massive transfusion protocol or clinician discretion)
2. Existing hospital inpatients who develop an AUGIB
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
John Radcliffe Hospital
NHS Blood and Transplant Research & Development (UK)
National R&D Office
500 North Bristol Park
NHS Blood and Transplant [NHSBT] (UK)
Funding Body Type
Funding Body Subtype
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
2013 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/23706959
2013 statistical analysis plan in: http://www.ncbi.nlm.nih.gov/pubmed/23837630
2014 strategies in: http://www.ncbi.nlm.nih.gov/pubmed/25416527
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/25926146
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/25956718
Jairath V, Kahan BC, Gray A, Doré CJ, Mora A, Dyer C, Stokes EA, Llewelyn C, Bailey AA, Dallal H, Everett SM, James MW, Stanley AJ, Church N, Darwent M, Greenaway J, Le Jeune I, Reckless I, Campbell HE, Meredith S, Palmer KR, Logan RF, Travis SP, Walsh TS, Murphy MF, Restrictive vs liberal blood transfusion for acute upper gastrointestinal bleeding: rationale and protocol for a cluster randomized feasibility trial., Transfus Med Rev, 2013, 27, 3, 146-153, doi: 10.1016/j.tmrv.2013.04.001.
Statistical analysis plan
Kahan BC, Jairath V, Murphy MF, Doré CJ, Update on the transfusion in gastrointestinal bleeding (TRIGGER) trial: statistical analysis plan for a cluster-randomised feasibility trial., Trials, 2013, 14, 206, doi: 10.1186/1745-6215-14-206.
HE Campbell, EA Stokes, D Bargo, RF Logan, A Mora, R Hodge, A Gray, MW James, AJ Stanley, SM Everett, AA Bailey, H Dallal, J Greenaway, C Dyer, C Llewelyn, TS Walsh, SPL Travis, MF Murphy, V Jairath on behalf of TRIGGER investigators, Costs and quality of life associated with acute upper gastrointestinal bleeding in the UK: cohort analysis of patients in a cluster randomised trial , BMJ Open, 2015, 5, e007230, doi: 10.1136/bmjopen-2014-007230 .
Jairath V, Kahan BC, Gray A, Doré CJ, Mora A, James MW, Stanley AJ, Everett SM, Bailey AA, Dallal H, Greenaway J, Le Jeune I, Darwent M, Church N, Reckless I, Hodge R, Dyer C, Meredith S, Llewelyn C, Palmer KR, Logan RF, Travis SP, Walsh TS, Murphy MF, Restrictive versus liberal blood transfusion for acute upper gastrointestinal bleeding (TRIGGER): a pragmatic, open-label, cluster randomised feasibility trial, Lancet, 2015 , 386, 9989, 137-144, doi: 10.1016/S0140-6736(14)61999-1.
Kahan BC, Cro S, Doré CJ, Bratton DJ, Rehal S, Maskell NA, Rahman N, Jairath V, Reducing bias in open-label trials where blinded outcome assessment is not feasible: strategies from two randomised trials, Trials, 2014, 15, 456, doi: 10.1186/1745-6215-15-456.