PRotEin Provision in Critical IllneSs (PRECISe)

January 13, 2023 updated by: Maastricht University Medical Center

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

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

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Belgium
      • Brussel, Belgium
        • Recruiting
        • UZ Brussel
        • Contact:
          • Elisabeth de Waele, MD, PhD
      • Genk, Belgium, 3600
      • 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:
    • Noord-Brabant
      • Eindhoven, Noord-Brabant, Netherlands, 5623 EJ
        • Recruiting
        • Catharina Ziekenhuis Eindhoven
        • Contact:
          • Ashley De Bie Dekker, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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.
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.
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)
Time Frame: Day 0, Day 30, 90 and 180 after index ICU admission.
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
Time Frame: Day 30, 90 and 180 after ICU admission
Overall survival
Day 30, 90 and 180 after ICU admission
Health-related Quality of Life - SF-36
Time Frame: Day 30, 90 and 180 after ICU admission
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
Time Frame: Day 30, 90 and 180 after ICU admission
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
Time Frame: Day 0, Day 30, 90 and 180 after index ICU admission
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
Time Frame: Day 0, Day 30, 90 and 180 after index ICU admission
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
Time Frame: Day 30, 90 and 180 after ICU admission.
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
Time Frame: Day 30, 90 and 180 after ICU admission
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
Time Frame: Day 30, 90 and 180 after ICU admission
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
Time Frame: Day 30, 90 and 180 after ICU admission.
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
Time Frame: During index ICU stay, up to 90 days.
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
Time Frame: During index ICU stay, up to 90 days.
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
Time Frame: During index ICU stay, up to 90 days.
Number of days on invasive mechanical ventilation.
During index ICU stay, up to 90 days.
Duration of index ICU stay
Time Frame: During index ICU stay, up to 90 days.
Number of days in ICU.
During index ICU stay, up to 90 days.
Duration of index hospital stay
Time Frame: From date of randomization until the date of index hospital discharge, assessed up to 6 months.
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
Time Frame: From date of randomization until the date of index hospital discharge, assessed up to 6 months.
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
Time Frame: During index ICU stay, up to 90 days.
Number of patients who contracted an ICU-acquired infection.
During index ICU stay, up to 90 days.
Incidence of acute kidney injury
Time Frame: During index ICU stay, up to 90 days.
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
Time Frame: During index ICU stay, up to 90 days.
Number of patients who received renal replacement therapy and days on it.
During index ICU stay, up to 90 days.
Incidence of hepatic dysfunction
Time Frame: During index ICU stay, up to 90 days.
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
Time Frame: During index ICU stay, up to 90 days.
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
Time Frame: During index ICU stay, up to 90 days.
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
Time Frame: Day 0, Day 30, 90 and 180 after index ICU admission.
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
Time Frame: Follow-up until 180 days after index ICU admission.
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
Time Frame: Follow-up until 180 days after index ICU admission.
Number of days at rehabilitation center.
Follow-up until 180 days after index ICU admission.
Time to return to work
Time Frame: Follow-up until 180 days after index ICU admission.
Number of days between ICU admission and return to work.
Follow-up until 180 days after index ICU admission.
Health economic analysis
Time Frame: From index ICU admission until 180 days.
Total health care costs.
From index ICU admission until 180 days.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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