Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2013

Open Access 01-12-2013 | Update

Update on the transfusion in gastrointestinal bleeding (TRIGGER) trial: statistical analysis plan for a cluster-randomised feasibility trial

Authors: Brennan C Kahan, Vipul Jairath, Michael F Murphy, Caroline J Doré

Published in: Trials | Issue 1/2013

Login to get access

Abstract

Background

Previous research has suggested an association between more liberal red blood cell (RBC) transfusion and greater risk of further bleeding and mortality following acute upper gastrointestinal bleeding (AUGIB).

Methods and design

The Transfusion in Gastrointestinal Bleeding (TRIGGER) trial is a pragmatic cluster-randomised feasibility trial which aims to evaluate the feasibility of implementing a restrictive vs. liberal RBC transfusion policy for adult patients admitted to hospital with AUGIB in the UK. This trial will help to inform the design and methodology of a phase III trial. The protocol for TRIGGER has been published in Transfusion Medicine Reviews. Recruitment began in September 2012 and was completed in March 2013. This update presents the statistical analysis plan, detailing how analysis of the TRIGGER trial will be performed. It is hoped that prospective publication of the full statistical analysis plan will increase transparency and give readers a clear overview of how TRIGGER will be analysed.

Trial registration

ISRCTN85757829
Literature
1.
Rockall TA, Logan RF, Devlin HB, Northfield TC: Incidence of and mortality from acute upper gastrointestinal haemorrhage in the united kingdom. Steering committee and members of the national audit of acute upper gastrointestinal haemorrhage. BMJ. 1995, 311: 222-226. 10.1136/bmj.311.6999.222.CrossRefPubMedPubMedCentral
2.
Wallis JP, Wells AW, Chapman CE: Changing indications for red cell transfusion from 2000 to 2004 in the North of England. Transfus Med. 2006, 16: 411-417. 10.1111/j.1365-3148.2006.00702.x.CrossRefPubMed
3.
Hearnshaw SA, Logan RF, Lowe D, Travis SP, Murphy MF, Palmer KR: Acute upper gastrointestinal bleeding in the UK: patient characteristics, diagnoses and outcomes in the 2007 UK audit. Gut. 2011, 60: 1327-1335. 10.1136/gut.2010.228437.CrossRefPubMed
4.
Jairath V, Kahan BC, Logan RF, Travis SP, Palmer KR, Murphy MF: Red blood cell transfusion practice in patients presenting with acute upper gastrointestinal bleeding: a survey of 815 UK clinicians. Transfusion. 2011, 51: 1940-1948. 10.1111/j.1537-2995.2011.03119.x.CrossRefPubMed
5.
Hearnshaw SA, Logan RF, Palmer KR, Card TR, Travis SP, Murphy MF: Outcomes following early red blood cell transfusion in acute upper gastrointestinal bleeding. Aliment Pharmacol Ther. 2010, 32: 215-224. 10.1111/j.1365-2036.2010.04348.x.CrossRefPubMed
6.
Restellini S, Kherad O, Jairath V, Martel M, Barkun AN: Red blood cell transfusion is associated with increased rebleeding in patients with nonvariceal upper gastrointestinal bleeding. Aliment Pharmacol Ther. 2013, 37: 316-322. 10.1111/apt.12170.CrossRefPubMed
7.
Villanueva C, Colomo A, Bosch A, Concepcion M, Hernandez-Gea V, Aracil C, Graupera I, Poca M, Alvarez-Urturi C, Gordillo J, Guarner-Argente C, Santalo M, Muniz E, Guarner C: Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013, 368: 11-21. 10.1056/NEJMoa1211801.CrossRefPubMed
8.
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. rationale and protocol for a cluster randomized feasibility trial. Transfus Med Rev. 2013, Epub ahead of print
9.
Rockall TA, Logan RF, Devlin HB, Northfield TC: Risk assessment after acute upper gastrointestinal haemorrhage. Gut. 1996, 38: 316-321. 10.1136/gut.38.3.316.CrossRefPubMedPubMedCentral
10.
Blatchford O, Murray WR, Blatchford M: A risk score to predict need for treatment for upper-gastrointestinal haemorrhage. Lancet. 2000, 356: 1318-1321. 10.1016/S0140-6736(00)02816-6.CrossRefPubMed
11.
White IR, Thompson SG: Adjusting for partially missing baseline measurements in randomized trials. Stat Med. 2005, 24: 993-1007. 10.1002/sim.1981.CrossRefPubMed
12.
Royston P, Sauerbrei W: Multivariable Model-Building: A Pragmatic Approach to Regression Analysis Based on Fractional Polynomials for Modelling Continuous Variables. 2008, Chichester UK: WileyCrossRef
13.
Donner A, Klar N: Design and Analysis of Cluster Randomization Trials in Health Research. 2000, New York: Oxford University Press Inc.
14.
Hayes RJ, Moulton LH: Cluster Randomised Trials. 2009, Boca Raton, FL: Chapman & Hall/CRCCrossRef
15.
Kahan BC, Morris TP: Assessing potential sources of clustering in individually randomised trials. BMC Med Res Methodol. 2013, 13: 58-10.1186/1471-2288-13-58.CrossRefPubMedPubMedCentral
16.
EuroQol-a new facility for the measurement of health-related quality of life. The EuroQol Group. Health Policy. 1990, 16: 199-208.
17.
Chan AW, Tetzlaff JM, Gotzsche PC, Altman DG, Mann H, Berlin JA, Dickersin K, Hróbjartsson A, Schulz KF, Parulekar WR, Krleza-Jeric K, Laupacis A, Moher D: SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013, 346: e7586-10.1136/bmj.e7586.CrossRefPubMedPubMedCentral
18.
Dwan K, Altman DG, Arnaiz JA, Bloom J, Chan AW, Cronin E, Decullier E, Easterbrook PJ, Von Elm E, Gamble C, Ghersi D, Ioannidis JP, Simes J, Williamson PR: Systematic review of the empirical evidence of study publication bias and outcome reporting bias. PLoS One. 2008, 3: e3081-10.1371/journal.pone.0003081.CrossRefPubMedPubMedCentral
19.
Dwan K, Altman DG, Cresswell L, Blundell M, Gamble CL, Williamson PR: Comparison of protocols and registry entries to published reports for randomised controlled trials. Cochrane Database Syst Rev. 2011, MR000031-
20.
Rising K, Bacchetti P, Bero L: Reporting bias in drug trials submitted to the Food and Drug Administration: review of publication and presentation. PLoS Med. 2008, 5: e217-10.1371/journal.pmed.0050217. discussion e217CrossRefPubMedPubMedCentral
21.
Hernandez AV, Steyerberg EW, Habbema JD: Covariate adjustment in randomized controlled trials with dichotomous outcomes increases statistical power and reduces sample size requirements. J Clin Epidemiol. 2004, 57: 454-460. 10.1016/j.jclinepi.2003.09.014.CrossRefPubMed
22.
Kahan BC, Morris TP: Reporting and analysis of trials using stratified randomisation in leading medical journals: review and reanalysis. BMJ. 2012, 345: e5840-10.1136/bmj.e5840.CrossRefPubMedPubMedCentral
23.
Turner EL, Perel P, Clayton T, Edwards P, Hernandez AV, Roberts I, Shakur H, Steyerberg EW: Covariate adjustment increased power in randomized controlled trials: an example in traumatic brain injury. J Clin Epidemiol. 2012, 65: 474-481. 10.1016/j.jclinepi.2011.08.012.CrossRefPubMed
24.
Kahan BC, Morris TP: Improper analysis of trials randomised using stratified blocks or minimisation. Stat Med. 2012, 31: 328-340. 10.1002/sim.4431.CrossRefPubMed
25.
Agresti A, Hartzel J: Strategies for comparing treatments on a binary response with multi-centre data. Stat Med. 2000, 19: 1115-1139. 10.1002/(SICI)1097-0258(20000430)19:8<1115::AID-SIM408>3.0.CO;2-X.CrossRefPubMed
26.
Pickering RM, Weatherall M: The analysis of continuous outcomes in multi-centre trials with small centre sizes. Stat Med. 2007, 26: 5445-5456. 10.1002/sim.3068.CrossRefPubMed
27.
Chu R, Thabane L, Ma J, Holbrook A, Pullenayegum E, Devereaux PJ: Comparing methods to estimate treatment effects on a continuous outcome in multicentre randomized controlled trials: a simulation study. BMC Med Res Methodol. 2011, 11: 21-10.1186/1471-2288-11-21.CrossRefPubMedPubMedCentral
28.
Kahan BC, Morris TP: Analysis of multicentre trials with continuous outcomes: when and how should we account for centre effects?. Stat Med. 2013, 32: 1136-1149. 10.1002/sim.5667.CrossRefPubMed
29.
Jennison C, Turnbull BW: Group Sequential Methods with Applications to Clinical Trials. 2000, Boca Raton, FL: Chapman & Hall/CRC Interdisciplinary Statistics
30.
Howard J, Malfroy M, Llewelyn C, Choo L, Hodge R, Johnson T, Purohit S, Rees DC, Tillyer L, Walker I, Fijnvandraat K, Kirby-Allen M, Spackman E, Davies SC, Williamson LM: The transfusion alternatives preoperatively in sickle cell disease (TAPS) study: a randomised, controlled, multicentre clinical trial. Lancet. 2013, 381: 930-938. 10.1016/S0140-6736(12)61726-7.CrossRefPubMed
Metadata
Title
Update on the transfusion in gastrointestinal bleeding (TRIGGER) trial: statistical analysis plan for a cluster-randomised feasibility trial
Authors
Brennan C Kahan
Vipul Jairath
Michael F Murphy
Caroline J Doré
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Trials / Issue 1/2013
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/1745-6215-14-206

Other articles of this Issue 1/2013

Trials 1/2013 Go to the issue

Study protocol

Alternative Imaging Modalities in Ischemic Heart Failure (AIMI-HF) IMAGE HF Project I-A: study protocol for a randomized controlled trial

Study protocol

Short-term psychotherapeutic treatment in adolescents engaging in non-suicidal self-injury: a randomized controlled trial

Study protocol

Effects of Anma massage therapy (Japanese massage) for gynecological cancer survivors: study protocol for a randomized controlled trial

Study protocol

SMART MOVE - a smartphone-based intervention to promote physical activity in primary care: study protocol for a randomized controlled trial

Study protocol

Incidence of unanticipated difficult airway using an objective airway score versus a standard clinical airway assessment: the DIFFICAIR trial – trial protocol for a cluster randomized clinical trial

Study protocol

Innovative interventions to promote positive dental health behaviors and prevent dental caries in preschool children: study protocol for a randomized controlled trial