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

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^*, Hasan M Al-Dorzi, Omar Aldibaasi, Musharaf Sadat, Jesna Jose, Dina Muharib, Haifa Algethamy, Abdulrahman A Al-Fares, Fahad Al-Hameed, Ahmed Mady, Ayman Kharaba, Ali Al Bshabshe, Khalid Maghrabi, Khalid AlGhamdi, Ghulam Rasool, Adnan AlGhamdi, Ghaleb A Almekhlafi, Jamal Chalabi, Haifaa Ibrahim AlHumedi, Maram Hasan SakkijhaNorah Khalid Alamrey, Amjad Sami Alaskar, Rabeah Hamad Alhutail, Kaouthar Sifaoui, Rakan Alqahtani, Ahmad S Qureshi, Mohammed Moneer Hejazi, Hatim Arishi, Samah AlQahtani, Amro Mohamed Ghazi, Saleh T Baaziz, Abeer Othman Azhar, Sara Fahad Alabbas, Mohammed AlAqeely, Ohoud AlOrabi, Aliaa Al-Mutawa, Maha AlOtaibi, Madiha Fawazy Elghannam, Mohammed Almaani, Sarah Fadel Buabbas, Wadiah Alawi M Alfilfil, Mohammed S Alshahrani, Joel Starkopf, Jean-Charles Preiser, Anders Perner, Jumana Hani AlMubarak, Wafa Mansoor Hazem, Talal Albrahim, Abdulaziz Al-Dawood, and the Saudi Critical Care Trials Group

^*Corresponding author for this work

Department of Intensive Care

3 Citations (Scopus)

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.

Original language	English
Article number	296
Journal	Trials
Volume	25
Issue number	1
ISSN	1745-6215
DOIs	https://doi.org/10.1186/s13063-024-08105-w
Publication status	Published - 2 May 2024

Keywords

Humans
Enteral Nutrition/methods
Critical Illness
Randomized Controlled Trials as Topic
Dietary Proteins/administration & dosage
Multicenter Studies as Topic
Data Interpretation, Statistical
Intensive Care Units
Quality of Life
Treatment Outcome
Respiration, Artificial
Time Factors
Critical illness
Randomized clinical trial
Nutrition
Protein
Statistical analysis plan

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Arabi, Y. M., Al-Dorzi, H. M., Aldibaasi, O., Sadat, M., Jose, J., Muharib, D., Algethamy, H., Al-Fares, A. A., Al-Hameed, F., Mady, A., Kharaba, A., Al Bshabshe, A., Maghrabi, K., AlGhamdi, K., Rasool, G., AlGhamdi, A., Almekhlafi, G. A., Chalabi, J., AlHumedi, H. I., ... and the Saudi Critical Care Trials Group (2024). Statistical analysis plan for the replacing protein via enteral nutrition in a stepwise approach in critically ill patients (REPLENISH) randomized clinical trial. Trials, 25(1), Article 296. https://doi.org/10.1186/s13063-024-08105-w

Arabi, YM, Al-Dorzi, HM, Aldibaasi, O, Sadat, M, Jose, J, Muharib, D, Algethamy, H, Al-Fares, AA, Al-Hameed, F, Mady, A, Kharaba, A, Al Bshabshe, A, Maghrabi, K, AlGhamdi, K, Rasool, G, AlGhamdi, A, Almekhlafi, GA, Chalabi, J, AlHumedi, HI, Sakkijha, MH, Alamrey, NK, Alaskar, AS, Alhutail, RH, Sifaoui, K, Alqahtani, R, Qureshi, AS, Hejazi, MM, Arishi, H, AlQahtani, S, Ghazi, AM, Baaziz, ST, Azhar, AO, Alabbas, SF, AlAqeely, M, AlOrabi, O, Al-Mutawa, A, AlOtaibi, M, Elghannam, MF, Almaani, M, Buabbas, SF, Alfilfil, WAM, Alshahrani, MS, Starkopf, J, Preiser, J-C, Perner, A, AlMubarak, JH, Hazem, WM, Albrahim, T, Al-Dawood, A & and the Saudi Critical Care Trials Group 2024, 'Statistical analysis plan for the replacing protein via enteral nutrition in a stepwise approach in critically ill patients (REPLENISH) randomized clinical trial', Trials, vol. 25, no. 1, 296. https://doi.org/10.1186/s13063-024-08105-w

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

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 = "Humans, Enteral Nutrition/methods, Critical Illness, Randomized Controlled Trials as Topic, Dietary Proteins/administration \& dosage, Multicenter Studies as Topic, Data Interpretation, Statistical, Intensive Care Units, Quality of Life, Treatment Outcome, Respiration, Artificial, Time Factors, Critical illness, Randomized clinical trial, Nutrition, Protein, Statistical analysis plan",

author = "Arabi, \{Yaseen M\} and Al-Dorzi, \{Hasan M\} and Omar Aldibaasi and Musharaf Sadat and Jesna Jose and Dina Muharib and Haifa Algethamy and Al-Fares, \{Abdulrahman A\} and Fahad Al-Hameed and Ahmed Mady and Ayman Kharaba and \{Al Bshabshe\}, Ali and Khalid Maghrabi and Khalid AlGhamdi and Ghulam Rasool and Adnan AlGhamdi and Almekhlafi, \{Ghaleb A\} and Jamal Chalabi and AlHumedi, \{Haifaa Ibrahim\} and Sakkijha, \{Maram Hasan\} and Alamrey, \{Norah Khalid\} and Alaskar, \{Amjad Sami\} and Alhutail, \{Rabeah Hamad\} and Kaouthar Sifaoui and Rakan Alqahtani and Qureshi, \{Ahmad S\} and Hejazi, \{Mohammed Moneer\} and Hatim Arishi and Samah AlQahtani and Ghazi, \{Amro Mohamed\} and Baaziz, \{Saleh T\} and Azhar, \{Abeer Othman\} and Alabbas, \{Sara Fahad\} and Mohammed AlAqeely and Ohoud AlOrabi and Aliaa Al-Mutawa and Maha AlOtaibi and Elghannam, \{Madiha Fawazy\} and Mohammed Almaani and Buabbas, \{Sarah Fadel\} and Alfilfil, \{Wadiah Alawi M\} and Alshahrani, \{Mohammed S\} and Joel Starkopf and Jean-Charles Preiser and Anders Perner and AlMubarak, \{Jumana Hani\} and Hazem, \{Wafa Mansoor\} and Talal Albrahim and Abdulaziz Al-Dawood and \{and the Saudi Critical Care Trials Group\}",

note = "{\textcopyright} 2024. The Author(s).",

year = "2024",

month = may,

day = "2",

doi = "10.1186/s13063-024-08105-w",

language = "English",

volume = "25",

journal = "Trials",

issn = "1745-6215",

publisher = "BioMed Central Ltd",

number = "1",

}

TY - JOUR

T1 - Statistical analysis plan for the replacing protein via enteral nutrition in a stepwise approach in critically ill patients (REPLENISH) randomized clinical trial

AU - Arabi, Yaseen M

AU - Al-Dorzi, Hasan M

AU - Aldibaasi, Omar

AU - Sadat, Musharaf

AU - Jose, Jesna

AU - Muharib, Dina

AU - Algethamy, Haifa

AU - Al-Fares, Abdulrahman A

AU - Al-Hameed, Fahad

AU - Mady, Ahmed

AU - Kharaba, Ayman

AU - Al Bshabshe, Ali

AU - Maghrabi, Khalid

AU - AlGhamdi, Khalid

AU - Rasool, Ghulam

AU - AlGhamdi, Adnan

AU - Almekhlafi, Ghaleb A

AU - Chalabi, Jamal

AU - AlHumedi, Haifaa Ibrahim

AU - Sakkijha, Maram Hasan

AU - Alamrey, Norah Khalid

AU - Alaskar, Amjad Sami

AU - Alhutail, Rabeah Hamad

AU - Sifaoui, Kaouthar

AU - Alqahtani, Rakan

AU - Qureshi, Ahmad S

AU - Hejazi, Mohammed Moneer

AU - Arishi, Hatim

AU - AlQahtani, Samah

AU - Ghazi, Amro Mohamed

AU - Baaziz, Saleh T

AU - Azhar, Abeer Othman

AU - Alabbas, Sara Fahad

AU - AlAqeely, Mohammed

AU - AlOrabi, Ohoud

AU - Al-Mutawa, Aliaa

AU - AlOtaibi, Maha

AU - Elghannam, Madiha Fawazy

AU - Almaani, Mohammed

AU - Buabbas, Sarah Fadel

AU - Alfilfil, Wadiah Alawi M

AU - Alshahrani, Mohammed S

AU - Starkopf, Joel

AU - Preiser, Jean-Charles

AU - Perner, Anders

AU - AlMubarak, Jumana Hani

AU - Hazem, Wafa Mansoor

AU - Albrahim, Talal

AU - Al-Dawood, Abdulaziz

AU - and the Saudi Critical Care Trials Group

PY - 2024/5/2

Y1 - 2024/5/2

N2 - 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.

AB - 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.

KW - Humans

KW - Enteral Nutrition/methods

KW - Critical Illness

KW - Randomized Controlled Trials as Topic

KW - Dietary Proteins/administration & dosage

KW - Multicenter Studies as Topic

KW - Data Interpretation, Statistical

KW - Intensive Care Units

KW - Quality of Life

KW - Treatment Outcome

KW - Respiration, Artificial

KW - Time Factors

KW - Critical illness

KW - Randomized clinical trial

KW - Nutrition

KW - Protein

KW - Statistical analysis plan

UR - https://www.scopus.com/pages/publications/85192043731

U2 - 10.1186/s13063-024-08105-w

DO - 10.1186/s13063-024-08105-w

M3 - Journal article

C2 - 38698442

SN - 1745-6215

VL - 25

JO - Trials

JF - Trials

IS - 1

M1 - 296

ER -

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

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