Replacing Protein Via Enteral Nutrition in Critically Ill Patients

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Critical Illness, Nutrition Disorders

Intervention / Treatment
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* Other: Replenish protein group
* Other: Standard protein group


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Replenish protein group<br>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<br>* 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<br>|
| Active Comparator: Standard protein group<br>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<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 90 day-all cause mortality | Mortality 90 days post randomization | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days alive at day 90 without life support | use of vasopressor/inotropic support, invasive mechanical ventilation and/or renal replacement therapy | 90 days | 
| Days alive and out of hospital at day 90 | 90 day survival after randomization | 90 days | 
| Bacteremia until 2 days of ICU stay | Any symptoms of bacteremia | until 2 days post ICU. | 
| New or progression of Skin Pressure Ulcers | anytime during ICU stay | ICU stay | 
| Functional assessment at day 90 | SARC-F screen for sarcopenia and EuroQoL | Day 90 |