Title: CALORIES: A phase III open multicentre randomised controlled trial comparing the clinical and cost-effectiveness of early nutritional support in critically ill patients via the parenteral versus the enteral route
Funder: Department of Health (England)

Abstract: Malnutrition remains a common problem in critically ill patients in NHS critical care units. The consequences of malnutrition include vulnerability to complications such as infection. Early nutritional support is therefore recommended for critically ill patients to address both deficiencies in nutritional state and related disorders in metabolism. Three meta-analyses of trials comparing parenteral with enteral nutritional support in critically ill patients have been published. Interpretation of their results is complicated by: the small sample sizes of the trials included; significant problems with the quality of the trials (only one fitting the criteria for a level I study i.e. concealed randomisation blinded outcome adjudication and analysis on intention-to-treat); and the patient populations in whom the trials were conducted. We have updated the most recent systematic review by Simpson and Doig (2005). The results indicate a non-significant survival parenteral nutritional support (relative risk 0.82 95% confidence interval 0.60 to 1.11) but an increased risk of infection (relative risk 1.77 95% confidence interval 1.19 to 2.63) compared with enteral nutritional support. Consequently parenteral nutritional support in the critical care unit remains controversial and no clear evidence exists as to the optimum method of delivery of nutritional support to critically ill patients.Currently nutritional support via the enteral route is the mainstay method of feeding patients in critical care but it is frequently associated with gastrointestinal intolerance and underfeeding. In contrast nutritional support via the parenteral route though more invasive and expensive is more likely to secure delivery of the intended nutrition. Historically parenteral nutritional support has been associated with more risks and complications (e.g. infectious complications) compared with enteral nutritional support but recent improvements in the delivery formulation and monitoring of parenteral nutrition justify further comparison and evaluation of these nutritional support techniques particularly in the early phase of the illness.CALORIES is a pragmatic open multicentre randomised controlled trial comparing the clinical and cost-effectiveness of early nutritional support in critically ill patients via the parenteral versus the enteral route.Primary objectives: # to estimate the effect of early (defined as within 36 hours of the date/time of original critical care unit admission) nutritional support via the parenteral route (PN) compared with the enteral route (EN) on mortality at 30 days; # to estimate the incremental cost-effectiveness of PN compared with EN at one year.Secondary objectivesTo compare PN with EN for: # duration of specific and overall organ support in the critical care unit; # infectious and non-infectious complications in the critical care unit; # duration of critical care unit and acute hospital length of stay; # mortality at discharge from the critical care unit and from hospital; # mortality at 90 days and at one year; # nutritional and health-related quality of life at 90 days and at one year; # resource use and costs at 90 days and at one year; # estimated lifetime incremental cost-effectiveness.Eligible patients who have provided informed consent or where agreement has been obtained from a consultee will be randomly allocated to receive either PN or EN for five days (i.e. 120 hours) unless they no longer require nutritional support or are discharged from the critical care unit. All other care is the responsibility of the treating clinician.To have 90% power with a type I error rate of 5% (two sided) to detect a 20% relative risk reduction (6.4% absolute risk reduction) from 32% in the EN arm to 25.6% in the PN arm will require a sample size of 1082 per arm. To allow for 2% crossovers/protocol violations (in each direction) and 2% loss to follow-up/withdrawal prior to 30 days (based on observed rates from the PAC-Man Study) a sample size of 1200 per arm (2400 total) will be required.Based on 20 critical care units recruiting an average of 60 patients per year patient recruitment is anticipated to be completed within two years. A full cost-effectiveness analysis (CEA) will be undertaken. All analyses will be lodged in a statistical analysis plan a priori before the investigators are unblinded to any trial outcomes. All analyses will be performed according to the intention-to-treat principle and results will be reported in accordance with the CONSORT statement.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: GENERIC HEALTH RELEVANCE