Harvey 2014.

Methods	RCT, multi‐centre, 2‐arm, parallel design
Participants	Total number of participants: 2400 Inclusion criteria ≥ 18 years of age Expected to require nutritional support for ≥ 2 days, within 36 hours of admission to ICU that was expected to last ≥ 3 days Exclusion criteria Participants could not be fed through either PN or EN route Received nutritional support in previous 7 days Had a gastrostomy or jejunostomy in situ Were pregnant Not expected to be in the UK for next 6 months Primary diagnoses Study authors reported co‐existing illnesses as liver, renal, respiratory, cardiovascular, and immunodeficiency Baseline characteristics EN group Age, mean (SD): 62.9 (± 15.4) years Gender, M/F: 725/472 APACHE II, mean (SD): 19.6 (± 7.0) SOFA, mean (SD): 9.6 (± 3.3) PN group Age, mean (SD): 63.3 (± 15.1) years Gender, M/F: 689/502 APACHE II, mean (SD): 19.6 (± 6.9) SOFA, mean (SD): 9.5 (± 3.4) Country: UK Setting: 33 ICUs
Interventions	EN group n = 1200; 1195 analysed; participants lost to follow‐up were not included in analysis, but protocol deviations were. See note Details: nasogastric or nasojejunal tube feeding for 5 days. Time of initiation of feeding: median 22 (IQR 16 to 28) hours. Target rate of 25 kcal/kg bodyweight/day, with goal to reach target within 48 to 72 hours. Prokinetics given for GRV cut‐offs at 200 to 500 mL. Use of international guidelines for glycaemic management, plus target level for serum glucose of < 180 mg/dL (10 mmol/L) Caloric intake received, mean (SD): 74 (± 44) kcal/kg PN group n = 1200; 1188 analysed; participants lost to follow‐up were not included in analysis, but protocol deviations were Details: central venous catheter placement. Target rate of delivery as for EN. Equivalent nutritional formula as EN, with same glycaemic management. IV feeding for 5 days, then weaned to gastric feeding. Time of initiation of feeding of feeding: median 24 (IQR 17 to 30) hours Caloric intake received, mean (SD): 89 (SD ± 44) kcal/kg
Outcomes	All‐cause mortality at 30 days, discharge, 90 days, and 1 year Length of ICU and hospital stay Infectious and non‐infectious complications (including hyperglycaemia, defined as any new episode of hyperglycaemia during study period) Duration of organ support
Notes	Funding/declarations of interest: NIHR Study dates: June 2011 to March 2014 Protocol deviations: EN: 30 did not receive assigned nutritional support, 26 received no nutritional support, 4 received PN. PN: 36 did not receive assigned nutritional support, 24 received no nutritional support, 12 received EN. All analysed as ITT. Additionally, there was a cross‐over of 18 participants in the EN group and 81 participants in the PN group, but these occurred towards the end of feeding and did not constitute protocol deviations.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Adequate sequence generation. 24‐hour telephone randomization system with computer algorithm used to balance groups in ICU
Allocation concealment (selection bias)	Low risk	Telephone randomization system and we assumed that allocation was concealed from investigators
Blinding of participants and personnel (performance bias) All outcomes	High risk	No details and we assumed investigators made no attempts to blind personnel
Blinding of outcome assessment (detection bias) All outcomes (except mortality)	Unclear risk	No details
Blinding of outcome assessment (detection bias) Mortality	Low risk	Lack of blinding unlikely to influence outcome data for mortality
Incomplete outcome data (attrition bias) All outcomes	Low risk	Small number lost to follow‐up and not included in ITT analysis. Some protocol deviations but less than 10%; ITT analysis used for these
Selective reporting (reporting bias)	Low risk	Prospective clinical trials registration ISRCTN17386141. Protocol outcomes were consistent with outcomes reported in published study
Baseline characteristics	Low risk	Appear comparable
Other bias	Unclear risk	Not enough information on nutritional formula to make judgement. "Standard stock supply" used. Glycaemic controls appeared the same