Transfusion in Gastrointestinal Bleeding (TRIGGER)

A Multi-centre, Feasibility, Cluster Randomised Controlled Trial Comparing Restrictive Versus Liberal Blood Transfusion Strategies in Adult Patients Admitted With Acute Upper Gastrointestinal Bleeding

Aim: To evaluate the feasibility and safety of a restrictive versus liberal red blood cell (RBC) transfusion policy in adult patients admitted with Acute Upper Gastrointestinal Bleeding (AUGIB) in order to inform the design of a definitive phase III randomised controlled trial.

Study Overview

• Status: Completed
• Conditions: Gastrointestinal Hemorrhage
• Intervention / Treatment: Other: Restrictive transfusion policy; Other: Liberal Transfusion Policy

Detailed Description

Trial overview: TRIGGER is a pragmatic trial aiming to recruit adult patients admitted with all cause AUGIB (non-variceal and variceal). The study will take place in six United Kingdon hospitals and they will be randomly allocated to a transfusion policy at the cluster level; three sites will be allocated to a restrictive transfusion policy and three to a liberal transfusion policy. Given the challenges that will be involved in early recruitment and cross-speciality care, a feasibility study is essential to determine whether a sufficient proportion of eligible patients can be recruited into the trial and that clinicians can adhere to the allocated transfusion policy. Recruitment will operate for 6 months in total. The investigators will compare recruitment rate, protocol adherence, clinical characteristics of patients recruited, exposure to RBC transfusions and the difference in Hb concentrations between the restrictive and liberal transfusion policies. The investigators will collect important clinical outcomes which the investigators anticipate being central to the phase III trial, including 28-day mortality, further bleeding rates and serious adverse events between the restrictive and liberal transfusion policies. The investigators will also collect data to enable us to plan a health economic evaluation and quality of life assessment for the phase III trial.

• Study Type: Interventional
• Enrollment (Actual): 936
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Oxford, United Kingdom
    • NHSBT Clinical Studies Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults aged 18 or over years presenting with AUGIB, defined by haematemesis or melaena.

Exclusion Criteria:

• Patients with whom the responsible clinician considers there is a need for immediate RBC transfusion prior to obtaining or regardless of the initial Hb result due to severity of bleeding.
• Existing hospital in-patients who develop AUGIB.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Restrictive Transfusion Policy; Participants allocated to this group will be eligible for transfusion once their Hb level is ≤ 8 g/dL after presentation to hospital. The objective for the attending clinician is to maintain the Hb level between 8.1-10 g/dL for the duration of hospital stay.	Other: Restrictive transfusion policy; Participants allocated to this group will be eligible for transfusion once their Hb level is ≤ 8 g/dL after presentation to hospital. The objective for the attending clinician is to maintain the Hb level between 8.1-10 g/dL for the duration of hospital stay.
Active Comparator: Liberal Transfusion Policy; Participants allocated to this group will be eligible for transfusion once their Hb level is ≤ 10 g/dL after presentation to hospital. The objective for the attending clinician is to maintain the Hb level between 10.1-12 g/dL for the duration of hospital stay.	Other: Liberal Transfusion Policy; Participants allocated to this group will be eligible for transfusion once their Hb level is ≤ 10 g/dL after presentation to hospital. The objective for the attending clinician is to maintain the Hb level between 10.1-12 g/dL for the duration of hospital stay.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence to the study protocol	Protocol adherence will be measured over time, to determine if adherence rates improve. Adherence rates will also be compared between transfusion arms.	up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Further Bleeding	Further bleeding up to Day 28: Further bleeding is a composite outcome that includes persistent bleeding (defined as any bleeding present at the end of the index endoscopy, regardless of whether endoscopic therapy was attempted or not), and recurrent bleeding. Recurrent bleeding is only assessed in patients without persistent bleeding, and must be confirmed by the presence of high-risk stigmata of bleeding either endoscopically, radiologically, or surgically. Recurrent bleeding should initially be suspected in the event of any combination of the following: fresh haematemesis, continuous melaena, or aspiration of fresh blood from a naso-gastric tube, with a pulse rate of >100 bpm, a fall in systolic blood pressure of >30mm Hg or a drop in Hb of >2g/dL in the preceding 24 hours. Persistent bleeding and recurrent bleeding will also be assessed separately.	up to 28 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Red Blood Cell exposure in patients	The difference in number of red blood cell units administered will be compared between the intervention groups up to discharge/death/Day 28 (whichever comes first).	up to 28 days
Selection bias	Clinical characteristics of patients in the two transfusion policies	6 months
Difference in Hb concentration Between Restrictive and Liberal Groups	The mean Hb values for patients will be compared between the treatment arms up to discharge/death/Day 28 (whichever comes first).	up to 28 days
Death	All-cause mortality up to Day 28.	up to 28 days
Need for therapeutic intervention at the index endoscopy	This includes any therapeutic modality performed for AUGIB at the index endoscopy.	up to 28 days
Need for surgery or radiological intervention to control bleeding		up to 28 days
Proportion of patients experiencing the composite endpoint of thromboembolic and ischaemic events up to Day 28	Includes myocardial infarction, stroke, pulmonary embolus, Deep Vein Thrombosis, acute kidney injury. Each component will also be assessed individually. See section 8.1.3 for a definition of ischaemic and thromboembolic events.	up to 28 days
Acute Transfusion reactions up to death/ discharge	Defined as a reaction occurring at any time up to 24 hours following a transfusion of a blood component.	up to 28 days
Infections	Any infection necessitating a prescription for the use of antibiotic treatment for a minimum of 5 days, provided the prescription is received before or on Day 28.	up to 28 days
Length of hospital stay		up to 28 days
Health related quality of life at Day 28		28 days

Collaborators and Investigators

• Sponsor: Dr Vipul Jairath
• Collaborators: NHS Blood and Transplant
• Investigators: Study Chair: Professor Michael F Murphy, NHS Blood and Transplant; Study Director: Vipul Jairath, NHSBT and Translational Gastroenterology Unit, Oxford, UK.

Publications and helpful links

General Publications

• Kahan BC, Jairath V. Outcome pre-specification requires sufficient detail to guard against outcome switching in clinical trials: a case study. Trials. 2018 May 2;19(1):265. doi: 10.1186/s13063-018-2654-z.
• Jairath V, Kahan BC, Gray A, Dore 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 Jul 11;386(9989):137-44. doi: 10.1016/S0140-6736(14)61999-1. Epub 2015 May 5.
• Campbell HE, Stokes EA, Bargo D, Logan RF, Mora A, Hodge R, Gray A, James MW, Stanley AJ, Everett SM, Bailey AA, Dallal H, Greenaway J, Dyer C, Llewelyn C, Walsh TS, Travis SP, Murphy MF, Jairath V; 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 Apr 29;5(4):e007230. doi: 10.1136/bmjopen-2014-007230.

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: July 24, 2012
• First Submitted That Met QC Criteria: April 2, 2014
• First Posted (Estimate): April 7, 2014

Study Record Updates

• Last Update Posted (Estimate): April 7, 2014
• Last Update Submitted That Met QC Criteria: April 2, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Transfusion in gastrointestinal bleeding
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Hemorrhage; Gastrointestinal Hemorrhage
• Other Study ID Numbers: 10-09-CSU; ID 12078 (Other Identifier: NIHR)