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Replacing Protein Via Enteral Nutrition in Critically Ill Patients (REPLENISH)

Primary Purpose

Critical Illness, Nutrition Disorders

Status

Recruiting

Phase

Not Applicable

Locations

Saudi Arabia

Study Type

Interventional

Intervention

Replenish protein group

Standard protein group

About this trial

This is an interventional basic science trial for Critical Illness

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

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.

Exclusion Criteria:

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

Sites / Locations

King Abdulaziz Medical cityRecruiting
Intensive Care Unit, King Abdulaziz Medical CityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Replenish protein group

Standard protein group

Arm Description

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

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

Outcomes

Primary Outcome Measures

90 day-all cause mortality

Mortality 90 days post randomization

Secondary Outcome Measures

Days alive at day 90 without life support

use of vasopressor/inotropic support, invasive mechanical ventilation and/or renal replacement therapy

Days alive and out of hospital at day 90

90 day survival after randomization

Bacteremia until 2 days of ICU stay

Any symptoms of bacteremia

New or progression of Skin Pressure Ulcers

anytime during ICU stay

Functional assessment at day 90

SARC-F screen for sarcopenia and EuroQoL

Full Information

NCT ID

NCT04475666

First Posted

June 7, 2020

Last Updated

January 8, 2023

Sponsor

King Abdullah International Medical Research Center

1. Study Identification

Unique Protocol Identification Number

NCT04475666

Brief Title

Replacing Protein Via Enteral Nutrition in Critically Ill Patients

Acronym

REPLENISH

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Recruiting

Study Start Date

September 21, 2020 (Actual)

Primary Completion Date

June 30, 2025 (Anticipated)

Study Completion Date

December 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

King Abdullah International Medical Research Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Critical Illness, Nutrition Disorders

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

2502 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Replenish protein group

Arm Type

Active Comparator

Arm Description

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

Arm Title

Standard protein group

Arm Type

Active Comparator

Arm Description

Intervention Type

Other

Intervention Name(s)

Replenish protein group

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

Standard protein group

Intervention Description

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

Primary Outcome Measure Information:

Title

90 day-all cause mortality

Description

Mortality 90 days post randomization

Time Frame

90 days

Secondary Outcome Measure Information:

Title

Days alive at day 90 without life support

Description

use of vasopressor/inotropic support, invasive mechanical ventilation and/or renal replacement therapy

Time Frame

90 days

Title

Days alive and out of hospital at day 90

Description

90 day survival after randomization

Time Frame

90 days

Title

Bacteremia until 2 days of ICU stay

Description

Any symptoms of bacteremia

Time Frame

until 2 days post ICU.

Title

New or progression of Skin Pressure Ulcers

Description

anytime during ICU stay

Time Frame

ICU stay

Title

Functional assessment at day 90

Description

SARC-F screen for sarcopenia and EuroQoL

Time Frame

Day 90

Other Pre-specified Outcome Measures:

Title

Safety outcomes during ICU stay

Description

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)

Time Frame

ICU stay

Title

Minor safety outcomes during ICU stay

Description

Feeding tolerance; Diarrhoea; Refeeding syndrome

Time Frame

ICU stay

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria(on ICU calendar day 4 or the morning of day 5) 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. Exclusion Criteria: 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Yaseen M Arabi, MD

Phone

0118011111

Ext

18855

arabi@ngha.med.sa

First Name & Middle Initial & Last Name or Official Title & Degree

Musharaf Sadat, MBBS

Phone

0118011111

Ext

10822

sadatmu@ngha.med.sa

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yaseen M Arabi, MD

Organizational Affiliation

King Saud Bin Abdulaziz University for Health Sciences

Official's Role

Principal Investigator

Facility Information:

Facility Name

King Abdulaziz Medical city

City

Jeddah

ZIP/Postal Code

21423

Country

Saudi Arabia

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Fahad M Al-Hameed, MD

Phone

00966 12 2266666

Ext

22771

HameedF@ngha.med.sa

First Name & Middle Initial & Last Name & Degree

Ohoud Al Orabi, MMedSC

Phone

0096612 2266666

Ext

28864

alorabioh@NGHA.MED.SA

First Name & Middle Initial & Last Name & Degree

Fahad Al-Hameed, MD

Facility Name

Intensive Care Unit, King Abdulaziz Medical City

City

Riyadh,

ZIP/Postal Code

11426

Country

Saudi Arabia

Individual Site Status

Recruiting

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

25733640

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.

Results Reference

background

PubMed Identifier

26773077

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.

Results Reference

background

PubMed Identifier

28098623

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.

Results Reference

background

PubMed Identifier

25499096

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.

Results Reference

background

PubMed Identifier

29486907

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.

Results Reference

background

PubMed Identifier

27589411

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.

Results Reference

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PubMed Identifier

30260486

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.

Results Reference

background

PubMed Identifier

28374096

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.

Results Reference

result

PubMed Identifier

34930871

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.

Results Reference

derived

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Replacing Protein Via Enteral Nutrition in Critically Ill Patients

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