Study protocol

Randomised trial of glutamine and selenium supplemented parenteral nutrition for critically ill patients. Protocol Version 9, 19 February 2007 known as SIGNET (Scottish Intensive care Glutamine or seleNium Evaluative Trial)

Peter JD Andrews¹ , Alison Avenell² , David W Noble⁴ , Marion K Campbell² , Claire G Battison¹ , Bernard L Croal² , William G Simpson⁵ , John Norrie² , Luke D Vale^2,3 , Jonathon Cook² , Robyn de Verteuil² and Anne C Milne² for The Trials Management Group

¹  Department of Anaesthesia, Critical Care & Pain Medicine, University of Edinburgh & Consultant, Critical Care, Western General Hospital Lothian University Hospitals Division, Edinburgh EH4 2XU, Scotland, UK

²  Health Services Research Unit, Health Sciences Building, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK

³  Health Economics Research Unit, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK

⁴  Department of Anaesthetics & Intensive Care, Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB25 2ZN Scotland, UK

⁵  Department of Clinical Biochemistry, Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB25 2ZN, Scotland, UK

author email corresponding author email

Trials 2007, 8:25doi:10.1186/1745-6215-8-25

Published:	20 September 2007

Abstract

Background

Mortality rates in the Intensive Care Unit and subsequent hospital mortality rates in the UK remain high. Infections in Intensive Care are associated with a 2–3 times increased risk of death. It is thought that under conditions of severe metabolic stress glutamine becomes "conditionally essential". Selenium is an essential trace element that has antioxidant and anti-inflammatory properties. Approximately 23% of patients in Intensive Care require parenteral nutrition and glutamine and selenium are either absent or present in low amounts. Both glutamine and selenium have the potential to influence the immune system through independent biochemical pathways. Systematic reviews suggest that supplementing parenteral nutrition in critical illness with glutamine or selenium may reduce infections and mortality. Pilot data has shown that more than 50% of participants developed infections, typically resistant organisms. We are powered to show definitively whether supplementation of PN with either glutamine or selenium is effective at reducing new infections in critically ill patients.

Methods/design

2 × 2 factorial, pragmatic, multicentre, double-blind, randomised controlled trial. The trial has an enrolment target of 500 patients. Inclusion criteria include: expected to be in critical care for at least 48 hours, aged 16 years or over, patients who require parenteral nutrition and are expected to have at least half their daily nutritional requirements given by that route.

Allocation is to one of four iso-caloric, iso-nitrogenous groups: glutamine, selenium, both glutamine & selenium or no additional glutamine or selenium. Trial supplementation is given for up to seven days on the Intensive Care Unit and subsequent wards if practicable. The primary outcomes are episodes of infection in the 14 days after starting trial nutrition and mortality. Secondary outcomes include antibiotic usage, length of hospital stay, quality of life and cost-effectiveness.

Discussion

To date more than 285 patients have been recruited to the trial from 10 sites in Scotland. Recruitment is due to finish in August 2008 with a further six months follow up. We expect to report the results of the trial in summer 2009.

Trial registration

This trial is registered with the International Standard Randomised Controlled Trial Number system. ISRCTN87144826