Rugeles 2013.

Methods	Study design: prospective, randomized controlled trial Study dates: August 2011 to July 2012 Setting: 30‐bed ICU of a tertiary‐level university hospital Country: Colombia
Participants	Inclusion criteria Age ≥18 years Admission to an ICU Expected to require EN through nasoenteric tube for at least 96 hours Exclusion criteria Participants with previous nutritional support in the same hospitalization Participants with concomitant parenteral nutrition Participants in transplantation programme Pregnancy Chronic renal failure Uraemic encephalopathy Diabetes Morbid obesity Do‐not‐resuscitate orders Sample size 80 participants: 40 participants in each group to detect an absolute difference in the SOFA score between the 2 measurements of 15% (8.0 expected total score and 1.2 for expected delta SOFA) and a SD between the difference of the means of 3.0. 80% power α error of 0.05 Age (years): intervention group: 53.3 (19.5); Control group: 55.7 (19.5) Sex (male, %): intervention group: 55; Control group: 60 Primary disease of the participants Reasons for admission‐ Intervention/Control group n (%) Respiratory disease 16 (40); 14 (35) CNS disorder 13 (33); 12 (30) Cardiac disease 2 (5); 4 (10) Gastrointestinal disease 0 (0); 3 (8) Other 9 (23); 7 (18) Disease severity score: APACHE II Intervention group: 13.9 ± 4.8; Control group: 15.1 ± 6.2 Mechanical ventilation no. (%) Not available Comorbidities: not available Nutrition status: not available Level of inflammation: not available
Interventions	Intervention Group 1 (n = 40) Hypocaloric group: 15 kcal/kg/day, with more than 1.5 g of protein per kg of body weight Control Group 2 (n = 40) Control group: received standard nutritional regimen with a goal of 25 kcal/kg/day Co‐interventions "for both groups, it was used an enteral formula in continuous feeding. To reach the protein goal, the study group regimen was enriched with additional protein modules, based on soy protein diluted in water and administered in two daily boluses. Participants in the study group received hyperproteic regimen until day 7, if they needed any further enteral nutrition they were switched to standard nutritional regimen with a goal of 25 kcal/kg/day without protein boluses."
Outcomes	Primary outcome Delta SOFA at 48 hours Secondary outcomes SOFA score at baseline SOFA score at 48 hours SOFA score at 96 hours Participants achieving a delta SOFA of 2 or more Insulin requirements Hyperglycaemic events per day ICU length of stay, days Ventilator requirement (days) Subgroups Not available
Funding sources	This research was supported by an unrestricted grant from Lafrancol Colombia.
Declarations of interest	No potential conflict of interest relevant to this article was reported.
Notes	The first author sent us the final manuscript of the study before publication, and answered our questions about the average time of the participants on enteral nutrition, the standard deviation of the calories and proteins received by both groups, why they did not report mortality and the way they gave the protein supplements to achieve the double blinding.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomization was performed using dark sealed envelopes with computer‐generated random allocations.
Allocation concealment (selection bias)	Low risk	Randomization was performed using dark sealed envelopes with computer‐generated random allocations.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind clinical trial. Although one of the investigators was not blind: (quote:) "only one of the members of the team (JDR) knew patient allocation, prescribed the formulations, and supervised the administration of the regimens; but ICU staff, who decided on daily care patient, was blind to patient allocation". The authors, upon request, gave further explanations about how there was low risk of blinding being broken.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double‐blind clinical trial. Although one of the investigators was not blind (quote:) "only one of the members of the team (JDR) knew patient allocation, prescribed the formulations, and supervised the administration of the regimens; but ICU staff, who decided on daily care patient, was blind to patient allocation". The authors, upon request, gave further explanations about how there was low risk of blinding being broken.
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote: "only patients who completed 96 hours of follow‐up were considered for the analysis; patients who did not fulfil the follow‐up period were excluded, and the envelope was returned to the sequence for patient replacement, until completion of the sample size (40 in each group)". Although the inclusion criteria stated that "Study population consisted of adult patients (18 years or older) admitted in the ICU, who were expected to require enteral nutrition through nasoenteric tube for at least 96 hours.", having participants randomized, intervened, and then excluded if they did not have 96 hours of enteral feeding could lead to a high risk of selection bias. Especially if the primary endpoint was "change in SOFA score at 48 hours". The number of excluded participants was significant: "In total, 115 potential patients met the initial inclusion criteria for enrolment, but only 80 completed the follow‐up and were included in the per protocol analysis".
Selective reporting (reporting bias)	High risk	Mortality, a secondary outcome, was not reported. Nevertheless, upon request, the authors responded that given that they excluded participants that did not fulfil the 96 hours of enteral nutrition requirement, they did not report mortality because this result would have been biased (they only measured mortality in participants who completed the 96 hours). This is why they did not report it. This is correct, although the best thing would have been to perform an intention‐to‐treat analysis and also report premature deaths.
Other bias	Low risk	No evidence of other bias