The Effect of Higher Protein Dosing in Critically Ill Patients Ultrasound a Sub-study

Phase 3

Withdrawn

• Conditions: Malnutrition; Critical Illness
• Interventions: Other: Usual Care; Other: Higher Protein/Amino Acid Group; Other: Ultrasound measure

• Registration Number: NCT04242966
• Lead Sponsor: Clinical Evaluation Research Unit at Kingston General Hospital

Brief Summary

The investigators will evaluate the effects of of higher protein/amino acid dosing (≥2.2 g/kg/d) vs usual care of protein/amino acid dosing (≤1.2 g/kg/d) over muscle mass in nutritionally high risk ill patients.

Detailed Description

The EFFORT Ultrasound (US) is a sub study of the parent EFFORT trial; a multi-center, pragmatic, volunteer-driven, registry-based, randomized, clinical trial of 4000 nutritionally high-risk critically ill patients in the intensive care unit. Patients will be randomized to 1 of 2 treatment groups: a usual care 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.

Patients in the US sub-study will undergo the US measures at baseline (within 24 hours of randomization, 10 days post randomization (if still in hospital) and just prior to hospital discharge. In the event that hospital discharge is prior to day 10, the day 10 measure will not be done. To ensure standardization and quality in the measures, we have created high quality training materials and will have US films sent centrally to abstract all measurements. In the first 10 patients enrolled in the US sub-study, participating sites will conduct a run-in phase where their submitted data will be evaluated for quality and reliability (both intra and inter-rater reliability) to ensure subsequent measures are of high quality. Nutritional and clinical data for these patients will be included in the parent EFFORT trial but the US measures may be omitted if quality is poor.

The investigator has posed the following research question:

Primary Sub Study 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 the usual care prescription (≤1.2 gram/kg/day) on muscle mass and quality, and 60 day mortality?

The proposed hypothesis:

Compared to receiving the usual care 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 greater muscle mass, improved survival and a quicker rate of recovery.

Study Timeline

• Study First Submitted: 2019-05-24
• Study First Submitted QC: 2020-01-24
• Study First Posted: 2020-01-27
• Status Verified: 2020-06
• Last Update Submitted: 2020-06-16
• Last Update Posted: 2020-06-18
• Study Start: 2020-11-01
• Primary Completion: 2021-12-01
• Study Completion: 2022-12-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Usual Care	Usual Care	Patients will receive a usual protein/amino acid dose (≤1.2 g/kg/d)
Higher Protein/Amino Acid Group	Higher Protein/Amino Acid Group	Patients will receive a higher protein/amino acid dose (≥2.2 g/kg/d).
Higher Protein/Amino Acid Group	Ultrasound measure	Patients will receive a higher protein/amino acid dose (≥2.2 g/kg/d).
Usual Care	Ultrasound measure	Patients will receive a usual protein/amino acid dose (≤1.2 g/kg/d)

Primary Outcome Measures

Name	Time	Method
Change of Muscle quality of the quadriceps from baseline to day 10 post randomization	at baseline (within 24 hours of randomization, day 10 days post randomization (if still in hospital) and just prior to hospital discharge. In the event that hospital discharge is prior to day 10, the day 10 measure will not be done	Using ultrasound of quadriceps
Change of Muscle mass of the quadriceps from baseline to day 10 post randomization	at baseline (within 24 hours of randomization, day 10 days post randomization (if still in hospital) and just prior to hospital discharge. In the event that hospital discharge is prior to day 10, the day 10 measure will not be done	Using ultrasound of quadriceps