Clinical trial NCT04475666: Replacing Protein Via Enteral Nutrition in Critically Ill Patients
Official title: Replacing Protein Via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients: An International, Multicenter Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Critical Illness
Nutrition Disorders
Lead sponsor: King Abdullah International Medical Research Center
Sponsor class: OTHER
First posted: 2020-07-17
Enrollment: 2502
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Detailed description: The REPLENISH is a multicentric, international, open label, randomized controlled trial which will enroll subjects in intensive care unit. Patients will be randomized on day 4 of ICU admission. Until ICU day 4, protein requirement will be provided according to the local practice as long as no intravenous amino acids are given and the average protein intake in the first 4 days does not exceed 0.8 g/kg/day. On ICU day 4, patients will be randomized to one of the two treatment groups: one with standard prescription without supplemental proteins (maximum1.2 g/kg/day) from the primary polymeric formula and another 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.

Randomization will be stratified by suspected COVID-19 and then by site and the use of renal replacement therapy at the time of randomization (intermittent hemodialysis or continuous renal replacement therapy.

Eligibility criteria: Inclusion Criteria(on ICU calendar day 4 or the morning of day 5)

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

Exclusion Criteria:

1. 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.
2. 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.
3. Patients who received an average protein of more than 0.8g/kg/day in the first 4 ICU days.
4. Patients being fed entirely through oral route - i.e. those who are eating.
5. Pregnancy.
6. Burn patients.
7. Prisoners or those undergoing forced treatment.
8. Patients with hepatic encephalopathy or Child C liver cirrhosis
9. Inherited defect of amino acid metabolism.
10. Allergies to protein supplement

Primary outcomes:
measure: 90 day-all cause mortality
timeFrame: 90 days
Secondary outcomes:
measure: Days alive at day 90 without life support
timeFrame: 90 days
measure: Days alive and out of hospital at day 90
timeFrame: 90 days
measure: Bacteremia until 2 days of ICU stay
timeFrame: until 2 days post ICU.
measure: New or progression of Skin Pressure Ulcers
timeFrame: ICU stay
measure: Functional assessment at day 90
timeFrame: Day 90
Other outcomes:
measure: Safety outcomes during ICU stay
timeFrame: ICU stay
measure: Minor safety outcomes during ICU stay
timeFrame: ICU stay
Locations:
city: Jeddah
country: Saudi Arabia
facility: King Abdulaziz Medical city
city: Riyadh,
country: Saudi Arabia
facility: Intensive Care Unit, King Abdulaziz Medical City
Study officials:
affiliation: King Saud Bin Abdulaziz University for Health Sciences
name: Yaseen M Arabi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.