title: A multicentre, randomised controlled trial comparing the clinical effectiveness and cost-effectiveness of early nutritional support via the parenteral versus the enteral route in critically ill patients (CALORIES).
abstract: BACKGROUND
  Malnutrition is a common problem in critically ill patients in UK NHS critical care units. Early nutritional support is therefore recommended to address deficiencies in nutritional state and related disorders in metabolism. However, evidence is conflicting regarding the optimum route (parenteral or enteral) of delivery.
  
  
  OBJECTIVE
  To estimate the effect of early nutritional support via the parenteral route compared with the enteral route on mortality at 30 days and on incremental cost-effectiveness at 1 year. Secondary objectives were to compare the route of early nutritional support on duration of organ support; infectious and non-infectious complications; critical care unit and acute hospital length of stay; all-cause mortality at critical care unit and acute hospital discharge, at 90 days and 1 year; survival to 90 days and 1 year; nutritional and health-related quality of life, resource use and costs at 90 days and 1 year; and estimated lifetime incremental cost-effectiveness.
  
  
  METHODS
  A pragmatic, open, multicentre, parallel-group randomised controlled trial with an integrated economic evaluation.
  
  
  METHODS
  Adult general critical care units in 33 NHS hospitals in England.
  
  
  METHODS
  2400 eligible patients.
  
  
  METHODS
  Five days of early nutritional support delivered via the parenteral (n = 1200) and enteral (n = 1200) route.
  
  
  METHODS
  All-cause mortality at 30 days after randomisation and incremental net benefit (INB) (at £20,000 per quality-adjusted life-year) at 1 year.
  
  
  RESULTS
  By 30 days, 393 of 1188 (33.1%) patients assigned to receive early nutritional support via the parenteral route and 409 of 1195 (34.2%) assigned to the enteral route had died [p = 0.57; absolute risk reduction 1.15%, 95% confidence interval (CI) -2.65 to 4.94; relative risk 0.97 (0.86 to 1.08)]. At 1 year, INB for the parenteral route compared with the enteral route was negative at -£1320 (95% CI -£3709 to £1069). The probability that early nutritional support via the parenteral route is more cost-effective - given the data - is < 20%. The proportion of patients in the parenteral group who experienced episodes of hypoglycaemia (p = 0.006) and of vomiting (p < 0.001) was significantly lower than in the enteral group. There were no significant differences in the 15 other secondary outcomes and no significant interactions with pre-specified subgroups.
  
  
  CONCLUSIONS
  Blinding of nutritional support was deemed to be impractical and, although the primary outcome was objective, some secondary outcomes, although defined and objectively assessed, may have been more vulnerable to observer bias.
  
  
  CONCLUSIONS
  There was no significant difference in all-cause mortality at 30 days for early nutritional support via the parenteral route compared with the enteral route among adults admitted to critical care units in England. On average, costs were higher for the parenteral route, which, combined with similar survival and quality of life, resulted in negative INBs at 1 year.
  
  
  CONCLUSIONS
  Nutritional support is a complex combination of timing, dose, duration, delivery and type, all of which may affect outcomes and costs. Conflicting evidence remains regarding optimum provision to critically ill patients. There is a need to utilise rigorous consensus methods to establish future priorities for basic and clinical research in this area.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN17386141.
  
  
  BACKGROUND
  This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 28. See the NIHR Journals Library website for further project information.
authors.affiliation: Clinical Trials Unit, Intensive Care National Audit & Research Centre, London, UK.
authors.forename: Sheila E
authors.initials: SE
authors.lastname: Harvey
authors.affiliation: Clinical Trials Unit, Intensive Care National Audit & Research Centre, London, UK.
authors.forename: Francesca
authors.initials: F
authors.lastname: Parrott
authors.affiliation: Clinical Trials Unit, Intensive Care National Audit & Research Centre, London, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Harrison
authors.affiliation: Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: M Zia
authors.initials: MZ
authors.lastname: Sadique
authors.affiliation: Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Grieve
authors.affiliation: Clinical Trials Unit, Intensive Care National Audit & Research Centre, London, UK.
authors.forename: Ruth R
authors.initials: RR
authors.lastname: Canter
authors.affiliation: Clinical Trials Unit, Intensive Care National Audit & Research Centre, London, UK.
authors.forename: Blair Kp
authors.initials: BK
authors.lastname: McLennan
authors.affiliation: Clinical Trials Unit, Intensive Care National Audit & Research Centre, London, UK.
authors.forename: Jermaine Ck
authors.initials: JC
authors.lastname: Tan
authors.affiliation: Department of Nutrition and Dietetics, Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: Danielle E
authors.initials: DE
authors.lastname: Bear
authors.affiliation: Department of Nutrition and Dietetics, Imperial College Healthcare NHS Trust, London, UK.
authors.forename: Ella
authors.initials: E
authors.lastname: Segaran
authors.affiliation: Division of Asthma, Allergy and Lung Biopsy, King's College London, London, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Beale
authors.affiliation: National Institute for Health Research Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK.
authors.forename: Geoff
authors.initials: G
authors.lastname: Bellingan
authors.affiliation: Department of Critical Care, Imperial College Healthcare NHS Trust, London, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Leonard
authors.affiliation: National Institute for Health Research Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Mythen
authors.affiliation: Clinical Trials Unit, Intensive Care National Audit & Research Centre, London, UK.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Rowan
mesh_terms: D000368:Aged; D003362:Cost-Benefit Analysis; D016638:Critical Illness / Q000191:economics / Q000628:therapy*; D004739:England; D004750:Enteral Nutrition / Q000191:economics; D005260:Female; D017048:Health Care Costs; D006801:Humans; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D010288:Parenteral Nutrition / Q000191:economics; D011788:Quality of Life; D016019:Survival Analysis; D016896:Treatment Outcome