Replacing Protein Via Enteral Nutrition in Critically Ill Patients

Critical Illness Clinical Trial

— REPLENISH  

Official title:

Replacing Protein Via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients: An International, Multicenter Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04475666
• Other study ID #: RC19/414/R
• Status: Recruiting
• Phase: N/A
• Start date: September 21, 2020
• Est. completion date: December 30, 2025

Study information

• Verified date: December 2022
• Source: King Abdullah International Medical Research Center
• Contact: Yaseen M Arabi, MD
• Phone: 0118011111
• Email: arabi[@]ngha.med.sa
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2502
• Est. completion date: December 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Critical Illness
• Nutrition Disorders

Intervention

Other:
• Replenish protein group
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
• Standard protein group
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

Locations

Country	Name	City	State
Saudi Arabia	King Abdulaziz Medical city	Jeddah
Saudi Arabia	Intensive Care Unit, King Abdulaziz Medical City	Riyadh,

Sponsors (1)

Lead Sponsor	Collaborator
King Abdullah International Medical Research Center

Country where clinical trial is conducted

Saudi Arabia, 

References & Publications (8)

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. — View 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 — View 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. — View 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. — View 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. — View 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. — View 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. Erratum In: JPEN J Parenter Enteral Nutr. 2016 Nov;40(8):1200. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety outcomes during ICU stay	New episode of stage 2 or higher AKI by KDIGO criteria; 2. Pneumonia defined as episodes of newly confirmed pneumonia according to the modified CDC criteria; 3. Grade IV Acute Gastrointestinal injury (AGI)	ICU stay
Other	Minor safety outcomes during ICU stay	Feeding tolerance; Diarrhoea; Refeeding syndrome	ICU stay
Primary	90 day-all cause mortality	Mortality 90 days post randomization	90 days
Secondary	Days alive at day 90 without life support	use of vasopressor/inotropic support, invasive mechanical ventilation and/or renal replacement therapy	90 days
Secondary	Days alive and out of hospital at day 90	90 day survival after randomization	90 days
Secondary	Bacteremia until 2 days of ICU stay	Any symptoms of bacteremia	until 2 days post ICU.
Secondary	New or progression of Skin Pressure Ulcers	anytime during ICU stay	ICU stay
Secondary	Functional assessment at day 90	SARC-F screen for sarcopenia and EuroQoL	Day 90