Transfusion in Gastrointestinal Bleeding (TRIGGER)

• ClinicalTrials.gov Identifier: NCT02105532
• Recruitment Status: Completed
• First Posted: April 7, 2014
• Last Update Posted: April 7, 2014
• Sponsor: Dr Vipul Jairath
• Collaborator: NHS Blood and Transplant
• Information provided by (Responsible Party): Dr Vipul Jairath, NHS Blood and Transplant

Tracking Information

• First Submitted Date: July 24, 2012
• First Posted Date: April 7, 2014
• Last Update Posted Date: April 7, 2014
• Study Start Date: September 2012
• Actual Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 2, 2014)

Adherence to the study protocol [ Time Frame: up to 28 days ]

Protocol adherence will be measured over time, to determine if adherence rates improve. Adherence rates will also be compared between transfusion arms.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: April 2, 2014)

Further Bleeding [ Time Frame: up to 28 days ]

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.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: April 2, 2014)

• Red Blood Cell exposure in patients [ Time Frame: up to 28 days ]
  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).
• Selection bias [ Time Frame: 6 months ]
  Clinical characteristics of patients in the two transfusion policies
• Difference in Hb concentration Between Restrictive and Liberal Groups [ Time Frame: up to 28 days ]
  The mean Hb values for patients will be compared between the treatment arms up to discharge/death/Day 28 (whichever comes first).
• Death [ Time Frame: up to 28 days ]
  All-cause mortality up to Day 28.
• Need for therapeutic intervention at the index endoscopy [ Time Frame: up to 28 days ]
  This includes any therapeutic modality performed for AUGIB at the index endoscopy.
• Need for surgery or radiological intervention to control bleeding [ Time Frame: up to 28 days ]
• Proportion of patients experiencing the composite endpoint of thromboembolic and ischaemic events up to Day 28 [ Time Frame: up to 28 days ]
  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.
• Acute Transfusion reactions up to death/ discharge [ Time Frame: up to 28 days ]
  Defined as a reaction occurring at any time up to 24 hours following a transfusion of a blood component.
• Infections [ Time Frame: up to 28 days ]
  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.
• Length of hospital stay [ Time Frame: up to 28 days ]
• Health related quality of life at Day 28 [ Time Frame: 28 days ]

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Transfusion in Gastrointestinal Bleeding
• Official Title: A Multi-centre, Feasibility, Cluster Randomised Controlled Trial Comparing Restrictive Versus Liberal Blood Transfusion Strategies in Adult Patients Admitted With Acute Upper Gastrointestinal Bleeding
• Brief Summary: 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.
• 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
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Gastrointestinal Hemorrhage

Intervention

• 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.
• 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.

Study Arms

• 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.
  Intervention: Other: Restrictive transfusion policy
• 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.
  Intervention: Other: Liberal Transfusion Policy

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, 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 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 2, 2014): 936
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: August 2013
• Actual Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT02105532
• Other Study ID Numbers: 10-09-CSU; ID 12078 ( Other Identifier: NIHR )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Dr Vipul Jairath, NHS Blood and Transplant
• Study 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.

• PRS Account: NHS Blood and Transplant
• Verification Date: April 2014