Heidegger 2013.

Methods	RCT, multi‐centre, 2‐arm, parallel design
Participants	Total number of participants: 305 Inclusion criteria People who received < 60% of their energy target from EN at day 3 after admission to the ICU Expected to stay for > 5 days Expected to survive for > 7 days Had a functional gastrointestinal tract. Exclusion criteria People who were receiving PN Had persistent gastrointestinal dysfunction and ileus Were pregnant Refused to consent Had been readmitted to the ICU after previous randomization Primary diagnoses Shock Neurological Cardiac surgery Polytrauma Pneumonia Cardiac arrest Respiratory failure Myocardial infarction Acute pancreatitis Liver failure Other Baseline characteristics EN group Age, mean (SD): 60 (± 16) years Gender, M/F: 105/47 APACHE II, mean (SD): 23 (± 7) SAPS II, mean (SD): 47 (± 15) EN + PN group Age, mean (SD): 61 (± 16) years Gender, M/F: 110/43 APACHE II, mean (SD): 22 (± 7) SAPS II, mean (SD): 49 (± 17) Country: Switzerland Setting: 2 ICUs, medical and surgical
Interventions	EN group n = 152; 10 participants discontinued study due to protocol violations; ITT analysis Details: nasogastric tube feeding (preferable). All participants fed EN until day 3. Participants in EN group continued with EN feeding for 5 days as part of intervention period, then remained on EN for 28 days as required. Target rate of delivery for women 25 kcal/kg of ideal bodyweight/day, for men 30 kcal/kg of ideal bodyweight/day. Protein delivery at 1.2 g/kg of ideal bodyweight/day, formula consisted of polymeric, fibre‐enriched formulas, routinely prescribed in both hospitals, containing 1.05 to 1.62 kcal/mL of energy (18% proteins, 29% lipids (8% medium‐chain triglycerides), 53% carbohydrates). Prokinetics given if GRV ≥ 300 mL. Continuous IV insulin therapy to maintain blood glucose at lower than 8.5 mmol/L. Caloric intake received, mean (SD): 20 (± 7) kcal/kg/day for days 4 to 8 EN + PN group n = 153; 20 participants discontinued study due to protocol violations; ITT analysis Details: central or peripheral catheter placement. All participants fed with EN formula until day 3. Participants in EN + PN group supplemented with PN feeding for 5 days, then resumed with only EN for 28 days as required. Target rate of delivery as for EN. EN formula as above. Formula for PN consisted of 0.62‐1.37 kcal/mL of energy (20% proteins, 29% lipids (15% medium‐chain triglycerides), and 51% carbohydrates). Caloric intake received, mean (SD): 28 (± 5) kcal/kg/day for days 4 to 8
Outcomes	Nosocomial infections after day 8 until day 28 LOS in the ICU and hospital until day 28 Mortality in the ICU General mortality Duration of invasive mechanical ventilation
Notes	Funding/declarations of interest: Foundation Nutrition 2000Plus, ICU Quality Funds, Baxter, and Fresenius Kabi. Study authors reported that, "sponsors of study had no role in study design, data collection, data analysis, data interpretation, or writing of the report." Study dates: December 2008 to December 2010 Note: study authors reported number of infections, rather than number of participants with an infection, and we could not report this data because we did not know if a participant had more than 1 infection
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Adequate sequence generation. Computer‐generated randomization sequence
Allocation concealment (selection bias)	Low risk	Adequate allocation concealment. Sequentially numbered, sealed, opaque envelopes
Blinding of participants and personnel (performance bias) All outcomes	High risk	Some attempts to reduce risk of bias; study investigators involved in decisions regarding caloric goal were blinded. However, other investigators, personnel, and participants were not blinded
Blinding of outcome assessment (detection bias) All outcomes (except mortality)	Low risk	Quote: "The senior site investigator from each university hospital prospectively obtained information about infectious episodes in study patients from the other centre, and was unaware of the treatment groups assigned to patients." Attempts to reduce outcome assessor and statistician blinding sufficient for our review outcomes
Blinding of outcome assessment (detection bias) Mortality	Low risk	Assume blinding of outcome assessors for blinding; and lack of blinding unlikely to influence outcome data for mortality
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	20 participants in EN + PN group, and 10 participants in EN group discontinued study mostly due to protocol violation. Study authors used an ITT analysis. We noted an uneven number of losses between groups, with > 10% loss in the EN + PN group, and that death before 9 days was classed as protocol violation. We assumed that participants who died were included in mortality data for this study
Selective reporting (reporting bias)	Unclear risk	Quote: "registered with ClinicalTrials.gov, number NCT00802503" Prospective registration. All outcomes reported in trial register documents were consistent with reported outcomes. However, we noted changes to the trial registration documents after completion of the trial to state time point for data collection of infections between day 9 to day 28. We could not be certain whether this change affected the data reported in the published study
Baseline characteristics	Low risk	Appeared comparable
Other bias	Low risk	No other sources of bias identified. No evidence of differences in glycaemic controls or nutritional protocol