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. 2024 May 2;25(1):296.
doi: 10.1186/s13063-024-08105-w.

Statistical analysis plan for the replacing protein via enteral nutrition in a stepwise approach in critically ill patients (REPLENISH) randomized clinical trial

Yaseen M Arabi  1 , Hasan M Al-Dorzi  2 , Omar Aldibaasi  3 , Musharaf Sadat  2 , Jesna Jose  3 , Dina Muharib  4 , Haifa Algethamy  5 , Abdulrahman A Al-Fares  6 , Fahad Al-Hameed  7 , Ahmed Mady  4   8 , Ayman Kharaba  9 , Ali Al Bshabshe  10 , Khalid Maghrabi  11 , Khalid AlGhamdi  12 , Ghulam Rasool  8 , Adnan AlGhamdi  13 , Ghaleb A Almekhlafi  13   14 , Jamal Chalabi  15 , Haifaa Ibrahim AlHumedi  2 , Maram Hasan Sakkijha  2 , Norah Khalid Alamrey  2 , Amjad Sami Alaskar  2 , Rabeah Hamad Alhutail  13 , Kaouthar Sifaoui  9 , Rakan Alqahtani  16 , Ahmad S Qureshi  17 , Mohammed Moneer Hejazi  2 , Hatim Arishi  2 , Samah AlQahtani  2 , Amro Mohamed Ghazi  2 , Saleh T Baaziz  5 , Abeer Othman Azhar  5 , Sara Fahad Alabbas  5 , Mohammed AlAqeely  4 , Ohoud AlOrabi  7 , Aliaa Al-Mutawa  6 , Maha AlOtaibi  4 , Madiha Fawazy Elghannam  12 , Mohammed Almaani  18 , Sarah Fadel Buabbas  19 , Wadiah Alawi M Alfilfil  20 , Mohammed S Alshahrani  21 , Joel Starkopf  22 , Jean-Charles Preiser  23 , Anders Perner  24 , Jumana Hani AlMubarak  19 , Wafa Mansoor Hazem  20 , Talal Albrahim  21 , Abdulaziz Al-Dawood  2 ; and the Saudi Critical Care Trials Group
Collaborators, Affiliations

Statistical analysis plan for the replacing protein via enteral nutrition in a stepwise approach in critically ill patients (REPLENISH) randomized clinical trial

Yaseen M Arabi et al. Trials. .

Abstract

Background: The optimal amount and timing of protein intake in critically ill patients are unknown. REPLENISH (Replacing Protein via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial evaluates whether supplemental enteral protein added to standard enteral nutrition to achieve a high amount of enteral protein given from ICU day five until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve a moderate amount of enteral protein would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients.

Methods: In this multicenter randomized trial, critically ill patients will be randomized to receive supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition to achieve a high amount of enteral protein (range of 2-2.4 g/kg/day) or no supplemental enteral protein to achieve a moderate amount of enteral protein (0.8-1.2 g/kg/day). The primary outcome is 90-day all-cause mortality; other outcomes include functional and health-related quality-of-life assessments at 90 days. The study sample size of 2502 patients will have 80% power to detect a 5% absolute risk reduction in 90-day mortality from 30 to 25%. Consistent with international guidelines, this statistical analysis plan specifies the methods for evaluating primary and secondary outcomes and subgroups. Applying this statistical analysis plan to the REPLENISH trial will facilitate unbiased analyses of clinical data.

Conclusion: Ethics approval was obtained from the institutional review board, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia (RC19/414/R). Approvals were also obtained from the institutional review boards of each participating institution. Our findings will be disseminated in an international peer-reviewed journal and presented at relevant conferences and meetings.

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

Keywords: Critical illness; Nutrition; Protein; Randomized clinical trial; Statistical analysis plan.

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Conflict of interest statement

The authors declare that they have no competing interests.

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