Effect of high versus standard protein provision on functional recovery in people with critical illness (PRECISe): an investigator-initiated, double-blinded, multicentre, parallel-group, randomised controlledtrial in Belgium and the Netherlands

Abstract

Background Increased protein provision might ameliorate muscle wasting and improve long-term outcomes in critically ill patients. The aim of the PRECISe trial was to assess whether higher enteral protein provision (ie, 2<middle dot>0 g/kg per day) would improve health-related quality of life and functional outcomes in critically ill patients who were mechanically ventilated compared with standard enteral protein provision (ie, 1<middle dot>3 g/kg per day). Methods The PRECISe trial was an investigator-initiated, double-blinded, multicentre, parallel-group, randomised controlled trial in five Dutch hospitals and five Belgian hospitals. Inclusion criteria were initiation of invasive mechanical ventilation within 24 h of intensive care unit (ICU) admission and an expected duration of invasive ventilation of 3 days or longer. Exclusion criteria were contraindications for enteral nutrition, moribund condition, BMI less than 18 kg/m(2), kidney failure with a no dialysis code, or hepatic encephalopathy. Patients were randomly assigned to one of four randomisation labels, corresponding with two study groups (ie, standard or high protein; two labels per group) in a 1:1:1:1 ratio through an interactive web-response system. Randomisation was done via random permuted-block randomisation in varying block sizes of eight and 12, stratified by centre. Participants, care providers, investigators, outcome assessors, data analysts, and the independent data safety monitoring board were all blinded to group allocation. Patients received isocaloric enteral feeds that contained 1<middle dot>3 kcal/mL and 0<middle dot>06 g of protein/mL (ie, standard protein) or 1<middle dot>3 kcal/mL and 0<middle dot>10 g of protein/mL (ie, high protein). The study-nutrition intervention was limited to the time period during the patient's ICU stay in which they required enteral feeding, with a maximum of 90 days. The primary outcome was EuroQoL 5-Dimension 5-level (EQ-5D-5L) health utility score at 30 days, 90 days, and 180 days after randomisation, adjusted for baseline EQ-5D-5L health utility score. This trial was registered with ClinicalTrials.gov (NCT04633421) and is closed to new participants. Findings Between Nov 19, 2020, and April 14, 2023, 935 patients were randomly assigned. 335 (35<middle dot>8%) of 935 patients were female and 600 (64<middle dot>2%) were male. 465 (49<middle dot>7%) of 935 were assigned to the standard protein group and 470 (50<middle dot>3%) were assigned to the high protein group. 430 (92<middle dot>5%) of 465 patients in the standard protein group and 419 (89<middle dot>1%) of 470 patients in the high protein group were assessed for the primary outcome. The primary outcome, EQ-5D-5L health utility score during 180 days after randomisation (assessed at 30 days, 90 days, and 180 days), was lower in patients allocated to the high protein group than in those allocated to the standard protein group, with a mean difference of -0<middle dot>05 (95% CI -0<middle dot>10 to -0<middle dot>01; p=0<middle dot>031). Regarding safety outcomes, the probability of mortality during the entire follow-up was 0<middle dot>38 (SE 0<middle dot>02) in the standard protein group and 0<middle dot>42 (0<middle dot>02) in the high protein group (hazard ratio 1<middle dot>14, 95% CI 0<middle dot>92 to 1<middle dot>40; p=0<middle dot>22). There was a higher incidence of symptoms of gastrointestinal intolerance in patients in the high protein group (odds ratio 1<middle dot>76, 95% CI 1<middle dot>06 to 2<middle dot>92; p=0<middle dot>030). Incidence of other adverse events did not differ between groups. Interpretation High enteral protein provision compared with standard enteral protein provision resulted in worse health-related quality of life in critically ill patients and did not improve functional outcomes during 180 days after ICU admission.