PRotEin Provision in Critical IllneSs (PRECISe)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Critical Illness; Intensive Care Unit Acquired Weakness
• Intervention / Treatment: Dietary supplement: PRECISe protocol EN 8g protein/100kcal; Dietary supplement: PRECISe protocol EN 5g protein/100kcal

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.

• Study Type: Interventional
• Enrollment (Anticipated): 935
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Julia LM Bels, MD; Phone Number: +31 06 30480685; Email: [email protected]
• Study Contact Backup: Name: Rob JJ van Gassel, MD; Phone Number: +31 0633861656; Email: [email protected]

Study Locations

• Belgium
  • Brussel, Belgium
    • Recruiting
    • UZ Brussel
    • Contact: Elisabeth de Waele, MD, PhD
  • Genk, Belgium, 3600
    • Recruiting
    • Ziekenhuis Oost-Limburg
    • Contact: Dieter Mesotten; Email: [email protected]
    • Contact: Katrien Tartaglia; Email: [email protected]
  • Kortrijk, Belgium
    • Recruiting
    • AZ Groeninge
    • Contact: Stoffel Lamote, MD, PhD
  • Liège, Belgium
    • Recruiting
    • CHU Liège
    • Contact: Didier Ledoux, MD, PhD
  • Liège, Belgium
    • Recruiting
    • Chr de La Citadelle
    • Contact: Vincent Fraipont, MD, PhD
• Netherlands
  • Ede, Netherlands
    • Recruiting
    • Gelderse Vallei Ede
    • Contact: Arthur van Zanten, MD, PhD
  • Enschede, Netherlands
    • Recruiting
    • Medisch Spectrum Twente
    • Contact: Bert Beishuizen, MD, PhD
  • Heerlen, Netherlands
    • Recruiting
    • Zuyderland Medisch Centrum
    • Contact: Clarissa Scheeren, MD
  • Maastricht, Netherlands
    • Recruiting
    • Maastricht Universtair Medisch Centrum
    • Contact: Marcel van de Poll, MD, PhD
    • Contact: Julia Bels, MD; Phone Number: +31 (0) 6 30 48 06 85; Email: [email protected]
  • Noord-Brabant
    • Eindhoven, Noord-Brabant, Netherlands, 5623 EJ
      • Recruiting
      • Catharina Ziekenhuis Eindhoven
      • Contact: Ashley De Bie Dekker, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRECISe protocol EN (8g protein/100kcal); Enteral (EN) feed with 8 grams protein per 100 kcal (2.0 g/kg/day protein when on target). The caloric goal is 25 kcal/kg/day to be reached on day 4 of ICU admission.	Dietary supplement: PRECISe protocol EN 8g protein/100kcal; Enteral feed containing 8g protein/100kcal
Active Comparator: PRECISe protocol EN (5g protein/100kcal); Enteral (EN) feed with 5 grams protein per 100 kcal (1.2 g/kg/day protein when on target). The caloric goal is 25 kcal/kg/day to be reached on day 4 of ICU admission.	Dietary supplement: PRECISe protocol EN 5g protein/100kcal; Enteral feed containing 5g protein/100kcal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health Related Quality of Life (HRQL)	Overall difference in EQ-5D single summary index between intervention and control group over the three time-points combined, corrected for baseline. A higher summary index indicates better Health related Quality of Life.	Day 0, Day 30, 90 and 180 after index ICU admission.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival	Day 30, 90 and 180 after ICU admission
Health-related Quality of Life - SF-36	Short Form 36 (SF-36), ranging from 0 to 100. A higher score indicates a better Health-related Quality of Life.	Day 30, 90 and 180 after ICU admission
Mental health status - anxiety/depression	Hospital Anxiety and Depression Scale (HADS), ranging from 0 to 42. Questions 1, 3, 5, 7, 9, 11 and 13 measure symptoms of anxiety (range: 0-21). Questions 2, 4, 6, 8, 10, 12 and 14 measure symptoms of depression (range: 0-21). Higher scores indicate worse symptoms of anxiety and depression.	Day 30, 90 and 180 after ICU admission
Pain intensity	EQ-5D pain question, ranging from 1 to 5, corrected for baseline. A higher score indicates a more severe perception of pain.	Day 0, Day 30, 90 and 180 after index ICU admission
Self-reported health	EQ-5D Visual Analogue Scale (EQ-VAS), ranging from 0 to 100. A higher score indicates a better self-reported health.	Day 0, Day 30, 90 and 180 after index ICU admission
Mental health status - post-traumatic stress	Impact of Event Scale Revised (IES-R), ranging from 0 to 88. A higher score indicates worse symptoms of Post-Traumatic Stress Disorder.	Day 30, 90 and 180 after ICU admission.
Physical function - 6-minute walk test	6-minute walk test. Data collected during 6-minute walk test are pre- and post-test saturation and pulse and total distance walked with or without the use of any aids.	Day 30, 90 and 180 after ICU admission
Muscle and nerve function - MRC-sum score	Medical Research Council (MRC-)sum score, ranging from 0 to 60. A higher score indicates better muscle and nerve function.	Day 30, 90 and 180 after ICU admission
Muscle and nerve function - handgrip strength	Handgrip strength, assessed via a hand dynamometer and measured in kilograms (kg).	Day 30, 90 and 180 after ICU admission.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Administration of prokinetics	Number of patients who received a prokinetic and number of days on it.	During index ICU stay, up to 90 days.
Incidence of gastrointestinal intolerance/symptoms	Number of patients that experienced gastrointestinal intolerance or symptoms at any time during index ICU stay, i.e. vomiting, ischemia, diarrhea, abdominal distention, gastric paresis, bleeding/ulcer.	During index ICU stay, up to 90 days.
Duration of mechanical ventilation	Number of days on invasive mechanical ventilation.	During index ICU stay, up to 90 days.
Duration of index ICU stay	Number of days in ICU.	During index ICU stay, up to 90 days.
Duration of index hospital stay	Number of days in hospital.	From date of randomization until the date of index hospital discharge, assessed up to 6 months.
Incidence of ICU-readmission	Number of patients readmitted to the ICU during index hospital stay and number of readmissions per patient.	From date of randomization until the date of index hospital discharge, assessed up to 6 months.
Incidence of ICU-acquired infections	Number of patients who contracted an ICU-acquired infection.	During index ICU stay, up to 90 days.
Incidence of acute kidney injury	Number of patients with Acute Kidney Injury (AKI), defined as a serum creatinine level higher than 2 times baseline level.	During index ICU stay, up to 90 days.
Incidence and duration of renal replacement therapy	Number of patients who received renal replacement therapy and days on it.	During index ICU stay, up to 90 days.
Incidence of hepatic dysfunction	Number of patients with hepatic dysfunction, defined as a total bilirubin level > 3mg/dL.	During index ICU stay, up to 90 days.
Maximum and mean SOFA score	Sequential Organ Failure Assessment score (SOFA), ranging from 0 to 24. A higher score indicates more severe multi-organ failure.	During index ICU stay, up to 90 days.
Difference in mobilization treatment	Number of days and degree of daily mobilization (passive/active, in-bed cycling etc).	During index ICU stay, up to 90 days.
Difference in frailty	Rockwood Clinical Frailty Scale, ranging from 1 to 9, corrected for baseline. A higher score indicates a more severe degree of frailty.	Day 0, Day 30, 90 and 180 after index ICU admission.
Destination of hospital discharge	Destination of hospital discharge (home, rehabilitation center, care facility etc).	Follow-up until 180 days after index ICU admission.
Length of stay at rehabilitation facility	Number of days at rehabilitation center.	Follow-up until 180 days after index ICU admission.
Time to return to work	Number of days between ICU admission and return to work.	Follow-up until 180 days after index ICU admission.
Health economic analysis	Total health care costs.	From index ICU admission until 180 days.

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: Catharina Ziekenhuis Eindhoven; Universitair Ziekenhuis Brussel; General Hospital Groeninge; Ziekenhuis Oost-Limburg; Zuyderland Medisch Centrum; Centre Hospitalier Régional de la Citadelle; Centre Hospitalier Universitaire de Liege; Medisch Spectrum Twente; Gelderse Vallei Hospital
• Investigators: Principal Investigator: Marcel CG van de Poll, MD, PhD, Maastricht UMC+

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2020
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: October 23, 2020
• First Submitted That Met QC Criteria: November 17, 2020
• First Posted (Actual): November 18, 2020

Study Record Updates

• Last Update Posted (Actual): January 18, 2023
• Last Update Submitted That Met QC Criteria: January 13, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Enteral Nutrition; Respiratory failure; Catabolism; Dietary Proteins
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: NL73247.068.20; 80-85200-98-18574 (Other Grant/Funding Number: KCE-ZonMW (BeNeFIT))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No