Clinical trial NCT04633421: PRotEin Provision in Critical IllneSs
Official title: The Impact of High Versus Standard Enteral Protein Provision on Functional Recovery Following Intensive Care Admission: a Randomized Controlled, Multicenter, Parallel Group Trial in Mechanically Ventilated, Critically Ill Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Critical Illness
Intensive Care Unit Acquired Weakness
Keywords: Enteral Nutrition
Dietary Proteins
Respiratory failure
Catabolism
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: Ziekenhuis Oost-Limburg
name: Zuyderland Medisch Centrum
name: Gelderse Vallei Hospital
name: Medisch Spectrum Twente
name: Centre Hospitalier Universitaire de Liege
name: Centre Hospitalier Régional de la Citadelle
name: Universitair Ziekenhuis Brussel
name: General Hospital Groeninge
name: Catharina Ziekenhuis Eindhoven
First posted: 2020-11-18
Enrollment: 935
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Rapid skeletal muscle wasting during critical illness had a detrimental impact on both short and long term outcomes following ICU admission. Increased dietary protein delivery might attenuate skeletal muscle wasting and its subsequent effects on post-ICU function.

The investigators will conduct a 935 patient, randomised controlled, quadruple blinded parallel group trial to determine whether enteral nutrition with increased protein content in mechanically ventilated, critically ill patients is able to improve functional recovery.

Detailed description: ICU-acquired weakness (ICU-AW) is frequent among ICU survivors and negatively affects both short and long term outcomes. ICU-AW is the consequence of the body's reserves being depleted during critical illness and results in severe skeletal muscle wasting during the first week of ICU admission.Therefore, measures aimed at preserving muscle mass during critical illness and improving recovery after ICU discharge are urgently needed.

Retrospective observational cohort studies suggest that the administration of high protein nutrition is associated with improved survival and outcome. Current ICU guidelines recommend dietary protein delivery at 1.3 g/kg/day (ESPEN), or even up to 2.0 g/kg/day (ASPEN). However, strong prospective clinical evidence on the effectiveness and safety of high enteral protein delivery is lacking and urgently awaited. Therefore, the aim of the present study is to investigate the effect of high versus standard protein provision on the functional recovery of critically ill patients.

The focus on functional, patient-centered outcomes rather than traditional clinical endpoints like mortality is an important aspect and strength of the study. Previous nutritional intervention studies focusing primarily on improving mortality have repeatedly shown no effect. Therefore, it is nowadays increasingly recognized to move primary ICU trial endpoints away from classical outcomes, such as survival or length of stay, towards more functional outcomes, in line with the underlying pathophysiology.

Eligibility criteria: Inclusion Criteria:

* Adult (18 years or above) patient admitted to the ICU
* Unplanned ICU admission
* Invasive mechanical ventilation initiated \<24 hours of ICU admission
* Expected ICU stay on ventilator support of 3 days or more

Exclusion Criteria:

* Contraindication for enteral nutrition
* Moribund or expected withholding of treatment
* Kidney failure AND 'no-dialysis'-code on admission
* Hepatic encephalopathy.(West Haven grade 3 or 4)
* Body-mass index \< 18 kg/m2

Primary outcomes:
measure: Health Related Quality of Life (HRQL)
timeFrame: Day 0, Day 30, 90 and 180 after index ICU admission.
Secondary outcomes:
measure: Overall survival
timeFrame: Day 30, 90 and 180 after ICU admission
measure: Health-related Quality of Life - SF-36
timeFrame: Day 30, 90 and 180 after ICU admission
measure: Mental health status - anxiety/depression
timeFrame: Day 30, 90 and 180 after ICU admission
measure: Pain intensity
timeFrame: Day 0, Day 30, 90 and 180 after index ICU admission
measure: Self-reported health
timeFrame: Day 0, Day 30, 90 and 180 after index ICU admission
measure: Mental health status - post-traumatic stress
timeFrame: Day 30, 90 and 180 after ICU admission.
measure: Physical function - 6-minute walk test
timeFrame: Day 30, 90 and 180 after ICU admission
measure: Muscle and nerve function - MRC-sum score
timeFrame: Day 30, 90 and 180 after ICU admission
measure: Muscle and nerve function - handgrip strength
timeFrame: Day 30, 90 and 180 after ICU admission.
Other outcomes:
measure: Duration of mechanical ventilation
timeFrame: During index ICU stay, up to 90 days.
measure: Duration of index ICU stay
timeFrame: During index ICU stay, up to 90 days.
measure: Duration of index hospital stay
timeFrame: From date of randomization until the date of index hospital discharge, assessed up to 6 months.
measure: Hospital mortality
timeFrame: From index ICU admission until index hospital discharge, assessed up to 6 months.
measure: 30-day mortality
timeFrame: From index ICU admission until day 30.
measure: 60-day mortality
timeFrame: From index ICU admission until day 60.
measure: 90-day mortality
timeFrame: From index ICU admission until day 90.
measure: Time-to-discharge-alive
timeFrame: From index ICU admission until index hospital discharge, assessed up to 6 months.
measure: Days alive and at home at day 90
timeFrame: From index ICU admission until day 90.
measure: Nutritional adequacy
timeFrame: From index ICU admission until index ICU discharge, assessed up to 6 months.
measure: Administration of prokinetics
timeFrame: During index ICU stay, up to 90 days.
measure: Incidence of gastrointestinal intolerance/symptoms
timeFrame: During index ICU stay, up to 90 days.
measure: Incidence of ICU-readmission
timeFrame: From date of randomization until the date of index hospital discharge, assessed up to 6 months.
measure: Incidence of ICU-acquired infections
timeFrame: During index ICU stay, up to 90 days.
measure: Incidence of acute kidney injury
timeFrame: During index ICU stay, up to 90 days.
measure: Incidence and duration of renal replacement therapy
timeFrame: During index ICU stay, up to 90 days.
measure: Incidence of hepatic dysfunction
timeFrame: During index ICU stay, up to 90 days.
measure: Maximum and mean SOFA score
timeFrame: During index ICU stay, up to 90 days.
measure: Difference in mobilization treatment
timeFrame: During index ICU stay, up to 90 days.
measure: Difference in frailty
timeFrame: Day 0, Day 30, 90 and 180 after index ICU admission.
measure: Domain data EQ-5D
timeFrame: Day 30, 90 and 180 after ICU admission.
measure: Destination of hospital discharge
timeFrame: Follow-up until 180 days after index ICU admission.
measure: Length of stay at rehabilitation facility
timeFrame: Follow-up until 180 days after index ICU admission.
measure: Time to return to work
timeFrame: Follow-up until 180 days after index ICU admission.
measure: Health economic analysis
timeFrame: From index ICU admission until 180 days.
Locations:
city: Brussel
country: Belgium
facility: UZ Brussel
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Liège
country: Belgium
facility: CHR de la Citadelle
city: Liège
country: Belgium
facility: CHU Liège
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis Eindhoven
state: Noord-Brabant
city: Ede
country: Netherlands
facility: Gelderse Vallei Ede
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Heerlen
country: Netherlands
facility: Zuyderland Medisch Centrum
city: Maastricht
country: Netherlands
facility: Maastricht Universtair Medisch Centrum
Study officials:
affiliation: Maastricht UMC+
name: Marcel CG van de Poll, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Needham DM, Sepulveda KA, Dinglas VD, Chessare CM, Friedman LA, Bingham CO 3rd, Turnbull AE. Core Outcome Measures for Clinical Research in Acute Respiratory Failure Survivors. An International Modified Delphi Consensus Study. Am J Respir Crit Care Med. 2017 Nov 1;196(9):1122-1130. doi: 10.1164/rccm.201702-0372OC.