PRotEin Provision in Critical IllneSs

Study Overview
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Brief Summary
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Rapid skeletal muscle wasting during critical illness had a detrimental impact on both short and long term outcomes following ICU admission. Increased dietary protein delivery might attenuate skeletal muscle wasting and its subsequent effects on post-ICU function. The investigators will conduct a 935 patient, randomised controlled, quadruple blinded parallel group trial to determine whether enteral nutrition with increased protein content in mechanically ventilated, critically ill patients is able to improve functional recovery.

Detailed Description
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ICU-acquired weakness (ICU-AW) is frequent among ICU survivors and negatively affects both short and long term outcomes. ICU-AW is the consequence of the body's reserves being depleted during critical illness and results in severe skeletal muscle wasting during the first week of ICU admission.Therefore, measures aimed at preserving muscle mass during critical illness and improving recovery after ICU discharge are urgently needed. Retrospective observational cohort studies suggest that the administration of high protein nutrition is associated with improved survival and outcome. Current ICU guidelines recommend dietary protein delivery at 1.3 g/kg/day (ESPEN), or even up to 2.0 g/kg/day (ASPEN). However, strong prospective clinical evidence on the effectiveness and safety of high enteral protein delivery is lacking and urgently awaited. Therefore, the aim of the present study is to investigate the effect of high versus standard protein provision on the functional recovery of critically ill patients. The focus on functional, patient-centered outcomes rather than traditional clinical endpoints like mortality is an important aspect and strength of the study. Previous nutritional intervention studies focusing primarily on improving mortality have repeatedly shown no effect. Therefore, it is nowadays increasingly recognized to move primary ICU trial endpoints away from classical outcomes, such as survival or length of stay, towards more functional outcomes, in line with the underlying pathophysiology.

Official Title
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The Impact of High Versus Standard Enteral Protein Provision on Functional Recovery Following Intensive Care Admission: a Randomized Controlled, Multicenter, Parallel Group Trial in Mechanically Ventilated, Critically Ill Patients

Conditions
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Critical Illness, Intensive Care Unit Acquired Weakness

Intervention / Treatment
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* Dietary Supplement: PRECISe protocol EN 8g protein/100kcal
* Dietary Supplement: PRECISe protocol EN 5g protein/100kcal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (18 years or above) patient admitted to the ICU Unplanned ICU admission Invasive mechanical ventilation initiated <24 hours of ICU admission Expected ICU stay on ventilator support of 3 days or more Exclusion Criteria: Contraindication for enteral nutrition Moribund or expected withholding of treatment Kidney failure AND 'no-dialysis'-code on admission Hepatic encephalopathy.(West Haven grade 3 or 4) Body-mass index < 18 kg/m2

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRECISe protocol EN (8g protein/100kcal)<br>Enteral (EN) feed with 8 grams protein per 100 kcal (2.0 g/kg/day protein when on target). The caloric goal is 25 kcal/kg/day to be reached on day 4 of ICU admission. | Dietary Supplement: PRECISe protocol EN 8g protein/100kcal<br>* Enteral feed containing 8g protein/100kcal<br>|
| Active Comparator: PRECISe protocol EN (5g protein/100kcal)<br>Enteral (EN) feed with 5 grams protein per 100 kcal (1.3 g/kg/day protein when on target). The caloric goal is 25 kcal/kg/day to be reached on day 4 of ICU admission. | Dietary Supplement: PRECISe protocol EN 5g protein/100kcal<br>* Enteral feed containing 5g protein/100kcal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health Related Quality of Life (HRQL) | Overall difference in EQ-5D single summary index between intervention and control group over the three time-points combined, corrected for baseline. A higher summary index indicates better Health related Quality of Life. | Day 0, Day 30, 90 and 180 after index ICU admission. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival | Day 30, 90 and 180 after ICU admission | 
| Health-related Quality of Life - SF-36 | Short Form 36 (SF-36), ranging from 0 to 100. A higher score indicates a better Health-related Quality of Life. | Day 30, 90 and 180 after ICU admission | 
| Mental health status - anxiety/depression | Hospital Anxiety and Depression Scale (HADS), ranging from 0 to 42. Questions 1, 3, 5, 7, 9, 11 and 13 measure symptoms of anxiety (range: 0-21). Questions 2, 4, 6, 8, 10, 12 and 14 measure symptoms of depression (range: 0-21). Higher scores indicate worse symptoms of anxiety and depression. | Day 30, 90 and 180 after ICU admission | 
| Pain intensity | EQ-5D pain question, ranging from 1 to 5, corrected for baseline. A higher score indicates a more severe perception of pain. | Day 0, Day 30, 90 and 180 after index ICU admission | 
| Self-reported health | EQ-5D Visual Analogue Scale (EQ-VAS), ranging from 0 to 100. A higher score indicates a better self-reported health. | Day 0, Day 30, 90 and 180 after index ICU admission | 
| Mental health status - post-traumatic stress | Impact of Event Scale Revised (IES-R), ranging from 0 to 88. A higher score indicates worse symptoms of Post-Traumatic Stress Disorder. | Day 30, 90 and 180 after ICU admission. | 
| Physical function - 6-minute walk test | 6-minute walk test. Data collected during 6-minute walk test are pre- and post-test saturation and pulse and total distance walked with or without the use of any aids. | Day 30, 90 and 180 after ICU admission | 
| Muscle and nerve function - MRC-sum score | Medical Research Council (MRC-)sum score, ranging from 0 to 60. A higher score indicates better muscle and nerve function. | Day 30, 90 and 180 after ICU admission | 
| Muscle and nerve function - handgrip strength | Handgrip strength, assessed via a hand dynamometer and measured in kilograms (kg). | Day 30, 90 and 180 after ICU admission. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Enteral Nutrition, Dietary Proteins, Respiratory failure, Catabolism