Replacing Protein Via Enteral Nutrition in Critically Ill Patients

NCT04475666 | Recruiting DMC

• 1 other identifier: RC19/414/R
• Study Type: interventional
• Target: 2,502
• Locations: 1 country
• Sites: 2

Brief Summary

The investigator will investigate the effect of supplemental enteral protein (1.2 g/kg/day) added to standard formula to achieve high amount of enteral protein (range 2-2.4 g/kg/day) given from ICU day 5 until ICU discharge up to ICU day 90 as compared to no supplemental enteral protein to achieve moderate amount enteral protein (0.8-1.2 g/kg/day), given in conjunction with similar amounts of stepwise caloric administration in the two groups on all-cause 90-day mortality.

Conditions

Critical Illness; Nutrition Disorders

Outcome Measures

Primary Outcomes (1)

• 90 day-all cause mortality

  Mortality 90 days post randomization

  90 days

Secondary Outcomes (5)

• Days alive at day 90 without life support

  90 days

• Days alive and out of hospital at day 90

  90 days

• Bacteremia until 2 days of ICU stay

  until 2 days post ICU.

• New or progression of Skin Pressure Ulcers

  ICU stay

• Functional assessment at day 90

  Day 90

Other Outcomes (2)

• Safety outcomes during ICU stay

  ICU stay

• Minor safety outcomes during ICU stay

  ICU stay

Study Arms (2)

Replenish protein group

ACTIVE COMPARATOR

The subjects randomized to this group will receive the standard amount of proteins (maximum 1.2 g/kg/day) from the primary polymeric formula AND supplemental protein at 1.2 g/kg/day

Other: Replenish protein group

Standard protein group

ACTIVE COMPARATOR

The subjects randomized to this group will receive standard prescription without supplemental proteins (maximum1.2 g/kg/day) from the primary polymeric formula. No supplemental protein will be allowed

Other: Standard protein group

Interventions

Replenish protein group OTHER

For patients with Body mass index(BMI) \<30, use pre-ICU actual body weight(BW) for the calculation; if unavailable, use weight on ICU admission. For patients with BMI \>=30, use adjusted body weight

Replenish protein group

Standard protein group OTHER

For patients with BMI \<30, use pre-ICU actual BW for the calculation; if unavailable, use weight on ICU admission. For patients with BMI \>=30, use adjusted body weight

Standard protein group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18-years old
• Patient started on enteral nutrition (EN) via nasogastric/orogastric or duodenal or percutaneous endoscopic gastrostomy (PEG) or jejunostomy tubes.
• The patient is on invasive mechanical ventilation and unlikely to be discharged from ICU next day.

You may not qualify if:

• Lack of commitment to full life support or brain death. Patients with "Do Not Resuscitate" order but with commitment to ongoing life support can be enrolled.
• Patients on any amount of parenteral nutrition (PN) in ICU at the time of screening, whether PN is used alone or in combination with enteral nutrition. Non-nutritional calories (dextrose, propofol, citrate) not considered as PN.
• Patients who received an average protein of more than 0.8g/kg/day in the first 4 ICU days.
• Patients being fed entirely through oral route - i.e. those who are eating.
• Pregnancy.
• Burn patients.
• Prisoners or those undergoing forced treatment.
• Patients with hepatic encephalopathy or Child C liver cirrhosis
• Inherited defect of amino acid metabolism.
• Allergies to protein supplement

Sponsors & Collaborators

• King Abdullah International Medical Research Center: lead

Study Sites (2)

King Abdulaziz Medical city

Jeddah, Jeddah, 21423, Saudi Arabia

RECRUITING

Intensive Care Unit, King Abdulaziz Medical City

Riyadh, 11426, Saudi Arabia

RECRUITING

Related Publications (11)

• Arabi YM, Casaer MP, Chapman M, Heyland DK, Ichai C, Marik PE, Martindale RG, McClave SA, Preiser JC, Reignier J, Rice TW, Van den Berghe G, van Zanten ARH, Weijs PJM. The intensive care medicine research agenda in nutrition and metabolism. Intensive Care Med. 2017 Sep;43(9):1239-1256. doi: 10.1007/s00134-017-4711-6. Epub 2017 Apr 3.

  PMID: 28374096 BACKGROUND

• Liebau F, Wernerman J, van Loon LJ, Rooyackers O. Effect of initiating enteral protein feeding on whole-body protein turnover in critically ill patients. Am J Clin Nutr. 2015 Mar;101(3):549-57. doi: 10.3945/ajcn.114.091934. Epub 2015 Feb 4.

  PMID: 25733640 BACKGROUND

• McClave SA, Taylor BE, Martindale RG, Warren MM, Johnson DR, Braunschweig C, McCarthy MS, Davanos E, Rice TW, Cresci GA, Gervasio JM, Sacks GS, Roberts PR, Compher C; Society of Critical Care Medicine; American Society for Parenteral and Enteral Nutrition. Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr. 2016 Feb;40(2):159-211. doi: 10.1177/0148607115621863. No abstract available.

  PMID: 26773077 BACKGROUND

• Compher C, Chittams J, Sammarco T, Nicolo M, Heyland DK. Greater Protein and Energy Intake May Be Associated With Improved Mortality in Higher Risk Critically Ill Patients: A Multicenter, Multinational Observational Study. Crit Care Med. 2017 Feb;45(2):156-163. doi: 10.1097/CCM.0000000000002083.

  PMID: 28098623 BACKGROUND

• Weijs PJ, Looijaard WG, Beishuizen A, Girbes AR, Oudemans-van Straaten HM. Early high protein intake is associated with low mortality and energy overfeeding with high mortality in non-septic mechanically ventilated critically ill patients. Crit Care. 2014 Dec 14;18(6):701. doi: 10.1186/s13054-014-0701-z.

  PMID: 25499096 BACKGROUND

• Koekkoek WACK, van Setten CHC, Olthof LE, Kars JCNH, van Zanten ARH. Timing of PROTein INtake and clinical outcomes of adult critically ill patients on prolonged mechanical VENTilation: The PROTINVENT retrospective study. Clin Nutr. 2019 Apr;38(2):883-890. doi: 10.1016/j.clnu.2018.02.012. Epub 2018 Feb 17.

  PMID: 29486907 BACKGROUND

• Arabi YM, Aldawood AS, Al-Dorzi HM, Tamim HM, Haddad SH, Jones G, McIntyre L, Solaiman O, Sakkijha MH, Sadat M, Mundekkadan S, Kumar A, Bagshaw SM, Mehta S; PermiT trial group. Permissive Underfeeding or Standard Enteral Feeding in High- and Low-Nutritional-Risk Critically Ill Adults. Post Hoc Analysis of the PermiT Trial. Am J Respir Crit Care Med. 2017 Mar 1;195(5):652-662. doi: 10.1164/rccm.201605-1012OC.

  PMID: 27589411 BACKGROUND

• Heyland DK, Patel J, Bear D, Sacks G, Nixdorf H, Dolan J, Aloupis M, Licastro K, Jovanovic V, Rice TW, Compher C. The Effect of Higher Protein Dosing in Critically Ill Patients: A Multicenter Registry-Based Randomized Trial: The EFFORT Trial. JPEN J Parenter Enteral Nutr. 2019 Mar;43(3):326-334. doi: 10.1002/jpen.1449. Epub 2018 Sep 27.

  PMID: 30260486 BACKGROUND

• 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 JC, Perner A, AlMubarak JH, Hazem WM, Albrahim T, Al-Dawood A; and the Saudi Critical Care Trials Group. Statistical analysis plan for the replacing protein via enteral nutrition in a stepwise approach in critically ill patients (REPLENISH) randomized clinical trial. Trials. 2024 May 2;25(1):296. doi: 10.1186/s13063-024-08105-w.

  PMID: 38698442 DERIVED

• Arabi YM, Al-Dorzi HM, Sadat M, Muharib D, Algethamy H, Al-Hameed F, Mady A, AlGhamdi A, Almekhlafi GA, Al-Fares AA, Kharaba A, Al Bshabshe A, Maghrabi K, Al Ghamdi K, Rasool G, Chalabi J, AlHumedi HI, Sakkijha MH, Alamrey NK, Alhutail RH, Sifaoui K, Almaani M, 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, Aldibaasi O, Jose J, Starkopf J, Preiser JC, Perner A, Al-Dawood A; Saudi Critical Care Trials Group. Replacing protein via enteral nutrition in a stepwise approach in critically ill patients: the REPLENISH randomized clinical trial protocol. Trials. 2023 Jul 30;24(1):485. doi: 10.1186/s13063-023-07507-6.

  PMID: 37518058 DERIVED

• Al-Dorzi HM, Stapleton RD, Arabi YM. Nutrition priorities in obese critically ill patients. Curr Opin Clin Nutr Metab Care. 2022 Mar 1;25(2):99-109. doi: 10.1097/MCO.0000000000000803.

  PMID: 34930871 DERIVED

MeSH Terms

Conditions

Critical Illness; Nutrition Disorders

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases

Study Officials

• Yaseen M Arabi, MD

  King Saud Bin Abdulaziz University for Health Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yaseen M Arabi, MD

CONTACT

0118011111; arabi@ngha.med.sa

Musharaf Sadat, MBBS

CONTACT

0118011111; sadatmu@ngha.med.sa

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2020
• First Posted: July 17, 2020
• Study Start: September 21, 2020
• Primary Completion: November 30, 2025
• Study Completion: April 30, 2026
• Last Updated: September 8, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

SA (2)