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

Arabi YM 1 , Al-Dorzi HM 2 , Aldibaasi O 3 , Sadat M 2 , Jose J 3 , Muharib D 4 Show all authors , Algethamy H 5 , Al-Fares AA 6 , Al-Hameed F 7 , Mady A 4 , Kharaba A 8 , Al Bshabshe A 9 , Maghrabi K 10 , AlGhamdi K 11 , Rasool G 12 , AlGhamdi A 13 , Almekhlafi GA 13 , Chalabi J 14 , AlHumedi HI 2 , Sakkijha MH 2 , Alamrey NK 2 , Alaskar AS 2 , Alhutail RH 13 , Sifaoui K 8 , Alqahtani R 15 , Qureshi AS 16 , Hejazi MM 2 , Arishi H 2 , AlQahtani S 2 , Ghazi AM 2 , Baaziz ST 5 , Azhar AO 5 , Alabbas SF 5 , AlAqeely M 4 , AlOrabi O 7 , Al-Mutawa A 6 , AlOtaibi M 4 , Elghannam MF 11 , Almaani M 17 , Buabbas SF 18 , Alfilfil WAM 19 , Alshahrani MS 20 , Starkopf J 21 , Preiser JC 22 , Perner A 23 , AlMubarak JH 18 , Hazem WM 19 , Albrahim T 20 , Al-Dawood A 2 , and the Saudi Critical Care Trials Group

Affiliations 

  • 1 Intensive Care Department, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, King Abdullah International Medical Research Center, ICU, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. arabi@ngha.med.sa
  • 2 Intensive Care Department, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, King Abdullah International Medical Research Center, ICU, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
  • 3 King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
  • 4 Intensive Care Department, King Saud Medical City, Riyadh, Saudi Arabia
  • 5 Department of Anesthesia and Critical Care, King Abdulaziz University, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
  • 6 Department of Anesthesia, Critical Care Medicine and Pain Medicine, Al-Amiri Hospital, Ministry of Health, Kuwait City, Kuwait
  • 7 Intensive Care Department, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
  • 8 Pulmonary & Critical Care Departments, King Fahad Hospital, Critical Care Units- Madinah Region, Ministry of Health, Madinah, Saudi Arabia
  • 9 Department of Critical Care Medicine, Aseer Central Hospital, King Khalid University, Abha, Saudi Arabia
  • 10 Internal Medicine, Critical Care, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
  • 11 Internal Medicine, Critical Care, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia
  • 12 Department of Anesthesiology and Surgical Intensive Care, Tanta University Hospitals, Tanta, Egypt
  • 13 Department of Intensive Care Services, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
  • 14 Intensive Care Department, King Abdulaziz Medical City, King Abdullah International Medical Research Center, AlAhsa Ministry of National Guard Health Affairs, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
  • 15 Department of Critical Care, College of Medicine, King Saud University, Riyadh, Saudi Arabia
  • 16 Intensive Care Department, Prince Mohammed Bin Abdulaziz Hospital, Ministry of National Guard Health Affairs, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Madinah, Saudi Arabia
  • 17 Adult Critical Care Services, King Fahad Medical City, Riyadh, Saudi Arabia
  • 18 Department of Anesthesia, Critical Care and Pain Medicine, Jaber Al-Ahmed Al-Sabah Hospital, Kuwait City, Kuwait
  • 19 Department of Intensive Care, Prince Mohammed Bin Abdulaziz Hospital, Riyadh, Saudi Arabia
  • 20 Department of Emergency and Critical Care, King Fahad Hospital of the University, Imam Abdulrahman Bin Faisal University, Al Khobar, Saudi Arabia
  • 21 Clinic of Anaesthesiology and Intensive Care, University of Tartu, Tartu University Hospital, Tartu, Estonia
  • 22 Department of Intensive Care, Erasme University Hospital, Brussels, Belgium
  • 23 Department of Intensive Care, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Trials, 2024 May 02;25(1):296.
PMID: 38698442 DOI: 10.1186/s13063-024-08105-w

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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