The Effect of Higher Protein Dosing in Critically Ill Patients: A Multicenter Randomized Trial

Phase 1

• Conditions: utritionally high-risk critically ill mechanically ventilated patients. In this sub-study, eligible and enrolled patients randomized to the high protein dose group will achieve its protein goals by adding high protein PN to EN (combined EN/PN). For patients enrolled to the low dose group, goals can be achieved by EN only.; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2018-003703-19-DE
• Lead Sponsor: RWTH Aachen University represented by the Rector himself, represented by the Dean of the Medical Faculty

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-05-20
• Last Update Posted: 21 July 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 142

Inclusion Criteria

1. =18 years old;
2. Expected to remain mechanically ventilated for an additional 48 hours from screening;
3. And have one or more of the following risk factors that make them at high nutritional risk:
a.Low (=25) or High BMI (=35)
b.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.).
c.Frailty (Clinical Frailty Scale 5 or more from proxy)
d.Sarcopenia (SARC-F score of 4 or more from proxy)
e.From point of screening, projected duration of mechanical ventilation >4 days

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 32
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 110

Exclusion Criteria

1.>96 continuous hours of mechanical ventilation before enrollment
2.Expected death or withdrawal of life-sustaining treatments within 7 days from screening
3.Pregnancy
4.The responsible clinician feels that the patient either needs low or high protein
5.Absolute contraindication to EN
6.Severe metabolic disorders including electrolyte disorders, uncontrolled hyperglycemia, hyperlipidemia, hypophosphatemia.
7.Severe chronic liver disease (MELD-score >20) or acute fulminant hepatitis.
8.Metabolic disorders involving impaired nitrogen utilization
9.Not ambulating independently prior to illness that lead to ICU admission (use of gait aid permitted)
10.Lower extremity injury or impairments that prevents them walking prior to hospital discharge (e.g. amputation, knee/hip injury)
11.Pre-existing cognitive impairment or language barrier that prohibits outcomes assessment
12.Pre-existing primary severe systemic neuromuscular disease resulting in severe weakness pre-ICU (e.g., Guillain Barre)
13.Intracranial or spinal process affecting motor function
14.Patients in hospital >5 days prior to ICU admission

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To show the effect of providing combined EN/PN to the group prescribed a higher dose (=2.2 grams/kg/day) of protein/amino acid administration compared to a low group prescribed =1.2 gram/kg/day (EN only) on patient’s functional recovery as measured by 6 minute walk distance just prior to hospital discharge.;Secondary Objective: - MRC sum-Score at hospital discharge<br>- Hand held dynamometry at hospital discharge<br>- Hand grip dynamometry at hospital discharge<br>- SPPB & FSS-ICU at Hospital discharge<br>- Ultrasound quadriceps at Baseline, ICU discharge and hospital discharge <br>- Questionnaires by telephone survey at 6 months: SF-36, EQ-5D-5L, Katz ADL, Lawton IADL, Employment questionnaire, Living Location and Healthcare resource utilization.;Primary end point(s): Physical Functioning by 6-minute walk test;Timepoint(s) of evaluation of this end point: At Hospital Discharge

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Overall strength-upper and lower extremity <br>•Quadriceps force-lower extremity strength<br>•Distal strength-hand grip strength<br>•Overall Physical Functional status<br>•Discharge location (e.g. home vs. rehab)<br>•Body composition via Ultrasound<br>•Body composition via CT (when clinically available)<br>•Health-related quality of life<br>•Physical functioning<br>•Healthcare resource utilization;Timepoint(s) of evaluation of this end point: Only at Hospital discharge: Overall strength-upper and lower extremity, Quadriceps force-lower extremity strength, Distal strength-hand grip strength, Overall Physical Functional status, Body composition via CT (when clinically available).<br>At Baseline/Screening, ICU discharge & Hospital discharge: Body composition via Ultrasound.<br>Follow Up - Visit at 6 months: Health-related quality of life, Physical functioning, Healthcare resource utilization.