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

NCT04012333 | Withdrawn Phase 3 DMC

• 1 other identifier: 18-108
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The primary research question: In critically ill patients with nutrition 'risk factors', what is 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? The hypothesis: Compared to a control group reflective of usual care prescribing practices and an EN only approach, the administration of a higher dose protein/amino acids using EN and PN to nutritionally high-risk critically ill patients will be associated with improved functional outcome.

Conditions

Nutritional Disorder; Critical Illness; Malnutrition; Frailty; Sarcopenia

Outcome Measures

Primary Outcomes (1)

• 6-minute walking distance

  measured by performing a 6-minute walking test

  at hospital discharge, up to 12 weeks

Secondary Outcomes (13)

• Overall strength-upper and lower extremity

  at hospital discharge, up to 12 weeks

• Quadriceps force-lower extremity strength

  ICU and at hospital discharge, up to 12 weeks

• Distal strength-hand grip strength

  ICU and at hospital discharge, up to 12 weeks

• Overall Physical Functional status

  Baseline (questionnaire only) and SPPB & FSS- ICU at ICU and at hospital discharge, up to 12 weeks

• Overall Physical Functional status

  Baseline (questionnaire only) and SPPB & FSS- ICU at ICU and at hospital discharge, up to 12 weeks

Study Arms (2)

Intervention

EXPERIMENTAL

Patients will receive standard care plus OLIMEL 7,6%E or if no central venous access available PeriOLIMEL 2,5%E to reach protein targets: \>2.2g/kg/day

Drug: OLIMEL 7,6%E / PeriOLIMEL 2,5%E

Standard Care

NO INTERVENTION

Patients will receive standard care (enteral nutrition only) to stay below the protein level: \<1.2g/kg/day

Interventions

OLIMEL 7,6%E / PeriOLIMEL 2,5%E DRUG

OLIMEL 7,6%E will be administered via a central access whereas PeriOLIMEL 2,5%E will be administered peripherally.

Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years old;
• Expected to remain mechanically ventilated for an additional 48 hours from screening;
• And have one or more of the following risk factors that make them at high nutritional risk:
• 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

You may not qualify if:

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

Sponsors & Collaborators

• RWTH Aachen University: lead
• Clinical Evaluation Research Unit at Kingston General Hospital: collaborator

Study Sites (1)

University Hospital RWTH Aachen

Aachen, North Rhine-Westphalia, 52074, Germany

Location

Related Publications (1)

• Hill A, Heyland DK, Elke G, Schaller SJ, Stocker R, Haberthur C, von Loeffelholz C, Suchner U, Puthucheary ZA, Bear DE, Ney J, Clasen KC, Meybohm P, Lindau S, Laurentius T, Stoppe C. Meeting nutritional targets of critically ill patients by combined enteral and parenteral nutrition: review and rationale for the EFFORTcombo trial. Nutr Res Rev. 2020 Dec;33(2):312-320. doi: 10.1017/S0954422420000165. Epub 2020 Jul 16.

  PMID: 32669140 DERIVED

MeSH Terms

Conditions

Nutrition Disorders; Critical Illness; Malnutrition; Frailty; Sarcopenia

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Signs and Symptoms

Study Officials

• Christian Stoppe, MD

  University Hospital, Aachen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Study staff performing the functional outcome measurements will be blinded to study treatment group
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Intervention: enteral and parenteral nutrition to reach protein target of 2.2g/kg/day Control: only enteral nutrition to stay below protein target of 1.2g/kg/day

Study Record Dates

• First Submitted: July 3, 2019
• First Posted: July 9, 2019
• Study Start: June 1, 2020
• Primary Completion: March 1, 2022
• Study Completion: March 1, 2022
• Last Updated: October 27, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)