The Effect of Higher Protein Dosing in Critically Ill Patients

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
lower 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 low group
prescribed ≤1.2 gram/kg/day on 60 day mortality?

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 time to discharge alive from hospital?

The proposed hypothesis:

Compared to receiving lower 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 improved survival and a quicker
rate of recovery.

Inclusion Criteria:

1. ≥18 years old

2. Nutritionally 'high-risk' (meeting one of the below criteria)

1. Low (≤25) or High BMI (≥35)

2. 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.).

3. Frailty (Clinical Frailty Scale 5 or more from proxy)

4. Sarcopenia- (SARC-F score of 4 or more from proxy)

5. From point of screening, projected duration of mechanical ventilation >4 days

3. Requiring mechanical ventilation with actual or expected total duration of mechanical
ventilation >48 hours

Exclusion Criteria:

1. >96 continuous hours of mechanical ventilation before screening

2. Expected death or withdrawal of life-sustaining treatments within 7 days from
screening

3. Pregnant

4. The responsible clinician feels that the patient either needs low or high protein

5. Patient requires parenteral nutrition only and site does not have products to reach
the high protein dose group.