The Effect of Higher Protein Dosing in Critically Ill Patients

Study Overview
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Brief Summary
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The investigator will investigate the effects of higher protein/amino acid dosing (≥2.2 g/kg/d) vs usual protein/amino acid dosing (≤1.2 g/kg/d) on clinical outcomes in nutritionally high risk ill patients.

Detailed Description
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The EFFORT Study is a multi-center, pragmatic, volunteer-driven, registry-based, randomized, clinical trial of 4000 nutritionally high-risk critically ill patients in the intensive care unit (ICU). We anticipate over 100 sites participating internationally, with each site enrolling a minimum of 30 patients. Patients will be randomized to 1 of 2 treatment groups: a usual prescription (≤1.2 g/kg/d) or a higher prescription (≥2.2 g/kg/d) of protein. Other than the protein amount the patient is randomized to the remainder of care provided to randomized patient will be at the discretion of ICU providers. In both groups, targets will be achieved through any combination of enteral nutrition (high protein content in high group if available), protein supplements, and parenteral nutrition or amino acids only (as clinically available). The only difference between the 2 groups is the protein targets that are set. Similar efforts should be used in both groups to achieve at least 80% of these targets. The remainder of care provided to eligible patients will be at the discretion of ICU providers. The investigator has posed two research questions: Primary Research Question: In critically ill patients with nutrition 'risk factors', what is the effect of prescribing a higher dose (≥2.2 grams/kg/day) of protein/amino acid administration compared to a usual dose prescribed ≤1.2 gram/kg/day on time to discharge alive from hospital? Secondary Research Question: In critically ill patients with nutrition 'risk factors', what is the effect of prescribing a higher dose (≥2.2 grams/kg/day) of protein/amino acid administration compared to patients prescribed ≤1.2 gram/kg/day on 60 day mortality? The proposed hypothesis: Compared to receiving usual dose of protein/amino acids, the administration of a higher dose of protein/amino acids (a consequence of having a higher prescription) to nutritionally high-risk critically ill patients will be associated with a quicker rate of recovery and an improved survival.

Official Title
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The Effect of Higher Protein Dosing in Critically Ill Patients: A Multicenter Registry-based Randomized Trial

Conditions
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Critical Illness, Malnutrition

Intervention / Treatment
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* Other: Usual Protein/Amino Acid Group
* Other: Higher Protein/Amino Acid Group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years old Nutritionally 'high-risk' (meeting one of the below criteria) Low (≤25) or High BMI (≥35) Moderate to severe malnutrition (as defined by local assessments). We will document the means by which sites are making this determination and capture the elements of the assessment (history of weight loss, history of reduced oral intake, etc.). Frailty (Clinical Frailty Scale 5 or more from proxy) Sarcopenia- (SARC-F score of 4 or more from proxy) From point of screening, projected duration of mechanical ventilation >4 days Requiring mechanical ventilation with actual or expected total duration of mechanical ventilation >48 hours Exclusion Criteria: >96 continuous hours of mechanical ventilation before screening Expected death or withdrawal of life-sustaining treatments within 7 days from screening Pregnant The responsible clinician feels that the patient either needs low or high protein Patient requires parenteral nutrition only and site does not have products to reach the high protein dose group.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Usual Protein/Amino Acid Group<br>Patients will receive a usual protein/amino acid dose (≤1.2 g/kg/d) | Other: Usual Protein/Amino Acid Group<br>* Protein targets will be set using pre-ICU dry actual weight. For patients with BMI >30, ideal body weight based on a BMI of 25 will be used. We will endorse the guidelines for energy targets set forth by ASPEN/SCCM, especially as it pertains to the obese patient.<br>|
| Active Comparator: Higher Protein/Amino Acid Group<br>Patients will receive a higher protein/amino acid dose (≥2.2 g/kg/d). | Other: Higher Protein/Amino Acid Group<br>* Protein targets will be set using pre-ICU dry actual weight. For patients with BMI >30, ideal body weight based on a BMI of 25 will be used. We will endorse the guidelines for energy targets set forth by ASPEN/SCCM, especially as it pertains to the obese patient.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to discharge alive from hospital | This is a composite of mortality and length of stay, evaluated up to 60 days post randomization | 60 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 60-day mortality | Mortality 60 days post randomization | 60 day |