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. 2023 Jul 30;24(1):485.
doi: 10.1186/s13063-023-07507-6.

Replacing protein via enteral nutrition in a stepwise approach in critically ill patients: the REPLENISH randomized clinical trial protocol

Yaseen M Arabi  1   2   3   4 , Hasan M Al-Dorzi  5   6   7   8 , Musharaf Sadat  5   6   7 , Dina Muharib  9 , Haifa Algethamy  10 , Fahad Al-Hameed  11   12   13 , Ahmed Mady  9   14 , Adnan AlGhamdi  15 , Ghaleb A Almekhlafi  15 , Abdulrahman A Al-Fares  16 , Ayman Kharaba  17   18 , Ali Al Bshabshe  19 , Khalid Maghrabi  20 , Khalid Al Ghamdi  21 , Ghulam Rasool  7   11   12   22 , Jamal Chalabi  7   23   24 , Haifaa Ibrahim AlHumedi  5   6   7 , Maram Hasan Sakkijha  5   6   7 , Norah Khalid Alamrey  5   6   7 , Rabeah Hamad Alhutail  15 , Kaouthar Sifaoui  17   18 , Mohammed Almaani  25 , Rakan Alqahtani  26 , Ahmad S Qureshi  7   27 , Mohammed Moneer Hejazi  5   6   7   8 , Hatim Arishi  5   6   7   8 , Samah AlQahtani  5   6   7   8 , Amro Mohamed Ghazi  5   6   7   8 , Saleh T Baaziz  10 , Abeer Othman Azhar  10 , Sara Fahad Alabbas  10 , Mohammed AlAqeely  9 , Ohoud AlOrabi  7   11   12   22 , Aliaa Al-Mutawa  28 , Maha AlOtaibi  9 , Omar Aldibaasi  7 , Jesna Jose  7 , Joel Starkopf  29 , Jean-Charles Preiser  30 , Anders Perner  31 , Abdulaziz Al-Dawood  5   6   7   8 ; Saudi Critical Care Trials Group
Collaborators, Affiliations

Replacing protein via enteral nutrition in a stepwise approach in critically ill patients: the REPLENISH randomized clinical trial protocol

Yaseen M Arabi et al. Trials. .

Abstract

Background: Protein intake is recommended in critically ill patients to mitigate the negative effects of critical illness-induced catabolism and muscle wasting. However, the optimal dose of enteral protein remains unknown. We hypothesize that supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition formula to achieve high amount of enteral protein (range 2-2.4 g/kg/day) given from ICU day 5 until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve moderate amount enteral protein (0.8-1.2 g/kg/day) would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients.

Methods: The REPLENISH (Replacing Protein Via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial is an open-label, multicenter randomized clinical trial. Patients will be randomized to the supplemental protein group or the control group. Patients in both groups will receive the primary enteral formula as per the treating team, which includes a maximum protein 1.2 g/kg/day. The supplemental protein group will receive, in addition, supplemental protein at 1.2 g/kg/day starting the fifth ICU day. The control group will receive the primary formula without supplemental protein. The primary outcome is 90-day all-cause mortality. Other outcomes include functional and quality of life assessments at 90 days. The trial will enroll 2502 patients.

Discussion: The study has been initiated in September 2021. Interim analysis is planned at one third and two thirds of the target sample size. The study is expected to be completed by the end of 2025.

Trial registration: ClinicalTrials.gov Identifier: NCT04475666 . Registered on July 17, 2020.

Keywords: Critical illness; Functional outcomes; Mortality; Protein intake; Randomized controlled trial.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Timeline for screening, enrollment, and assessment for patients enrolled in REPLENISH trial. Asterisk (*) symbol signifies days 15, 16, 17, 18, 19, 20, 22, 23, 24, 25, 26, 27, and 29 to 89; SARC-F, screening test for sarcopenia; EQ-5D-5L, EuroQol 5-Dimension 5-Level questionnaire
See this image and copyright information in PMC

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