Replacing protein via enteral nutrition in a stepwise approach in critically ill patients: A pilot randomized controlled trial (REPLENISH pilot trial)

Background and aims: The optimal amount of protein intake in critically ill patients is unclear. The objective of this pilot trial is to assess the feasibility of a large randomized controlled trial testing higher versus lower protein intake in critically ill patients. Methods: In this pilot randomized controlled trial (REPLacing Protein via Enteral Nutrition in a Stepwise ApproacH in critically ill patients: A pilot randomized controlled trial (REPLENISH pilot trial), critically ill patients underwent 2-step screening for eligibility on ICU day 1 and 5. Patients with renal disease were excluded. Eligible patients were randomized into REPLENISH group (target protein 1.8-2.2 g kg/day) and Standard group (target protein 0.8-1.0 g/kg/day) from day 6-14 after ICU admission. Dietitians adjusted caloric and protein intake throughout the study period (Day 1-14) to maintain similar caloric targets of permissive underfeeding (40-60% of estimated energy expenditure) in both study groups. Results: Of 704 patients screened at 3 centers in Saudi Arabia from May 2018 to May 2019, only 63 (8.9%) were eligible and 40 (5.7% of screened) were randomized with an average of 2 patients enrolled in the trial per month. Among eligible patients, the consenting rate was high at 89%. During the intervention period, patients in the REPLENISH group (N = 21) had a modestly higher protein intake (median of 1.30 g/kg/day (Q1 Q3: 1.11, 1.57)) than those in the standard group (median of 0.77 g/kg/day (Q1 Q3: 0.57, 1.00); P = 0.0004). Only 31.4% of patients in the whole cohort had >80% of prescribed protein. The duration of daily interruption of feeding was almost 4 h in both groups. The 90-day mortality for the patient study cohort was 20.5%. Anthropometric and muscle strength measurements were performed in less than 50% of patients. Conclusions: This pilot trial highlighted several areas for improvement in the study protocol before launching a large randomized controlled trial. The restrictive eligibility criteria, the complex adjustments of protein and energy and some of the outcome measurements were identified as targets for modifi-cations, to improve enrollment and generalizability and to enhance adherence to study interventions and measurements. Trial registration: clinicaltrials.gov identifier: NCT03480555. (C) 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.