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PRotEin Provision in Critical IllneSs (PRECISe)

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ClinicalTrials.gov Identifier: NCT04633421
Recruitment Status : Recruiting
First Posted : November 18, 2020
Last Update Posted : March 24, 2021
Sponsor:
Collaborators:
Ziekenhuis Oost-Limburg
Zuyderland Medisch Centrum
Gelderse Vallei Hospital
Medisch Spectrum Twente
Centre Hospitalier Universitaire de Liège
Centre Hospitalier Régional de la Citadelle
Universitair Ziekenhuis Brussel
General Hospital Groeninge
Information provided by (Responsible Party):
Maastricht University Medical Center

Tracking Information
First Submitted Date  ICMJE October 23, 2020
First Posted Date  ICMJE November 18, 2020
Last Update Posted Date March 24, 2021
Actual Study Start Date  ICMJE November 19, 2020
Estimated Primary Completion Date May 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 17, 2020)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 17, 2020)
  • Overall survival [ Time Frame: Day 30, 90 and 180 after ICU admission ]
    Overall survival
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: November 17, 2020)
  • 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.
  • 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.
  • Duration of mechanical ventilation [ Time Frame: During index ICU stay, up to 90 days. ]
    Number of days on invasive mechanical ventilation.
  • Duration of index ICU stay [ Time Frame: During index ICU stay, up to 90 days. ]
    Number of days in ICU.
  • 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.
  • 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.
  • Incidence of ICU-acquired infections [ Time Frame: During index ICU stay, up to 90 days. ]
    Number of patients who contracted an ICU-acquired infection.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • 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.
  • 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).
  • Length of stay at rehabilitation facility [ Time Frame: Follow-up until 180 days after index ICU admission. ]
    Number of days at rehabilitation center.
  • 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.
  • Health economic analysis [ Time Frame: From index ICU admission until 180 days. ]
    Total health care costs.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE PRotEin Provision in Critical IllneSs
Official Title  ICMJE 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
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 824 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Study feeds will be blinded. Dosing of intervention will be volume based, with the same volume targets for both groups. Differences in composition of study feeds will result in differences in protein intake at similar volume administration.
Primary Purpose: Treatment
Condition  ICMJE
  • Critical Illness
  • Intensive Care Unit Acquired Weakness
Intervention  ICMJE
  • Dietary Supplement: PRECISe protocol EN 8g protein/100kcal
    Enteral feed containing 8g protein/100kcal
  • Dietary Supplement: PRECISe protocol EN 5g protein/100kcal
    Enteral feed containing 5g protein/100kcal
Study Arms  ICMJE
  • 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.
    Intervention: Dietary Supplement: PRECISe protocol EN 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.
    Intervention: Dietary Supplement: PRECISe protocol EN 5g protein/100kcal
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 17, 2020)
824
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2023
Estimated Primary Completion Date May 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Julia LM Bels, MD 06 30480685 ext +31 precise@mumc.nl
Contact: Rob JJ van Gassel, MD 0633861656 ext +31 r.vangassel@maastrichtuniversity.nl
Listed Location Countries  ICMJE Belgium,   Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04633421
Other Study ID Numbers  ICMJE NL73247.068.20
80-85200-98-18574 ( Other Grant/Funding Number: KCE-ZonMW (BeNeFIT) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Maastricht University Medical Center
Study Sponsor  ICMJE Maastricht University Medical Center
Collaborators  ICMJE
  • Ziekenhuis Oost-Limburg
  • Zuyderland Medisch Centrum
  • Gelderse Vallei Hospital
  • Medisch Spectrum Twente
  • Centre Hospitalier Universitaire de Liège
  • Centre Hospitalier Régional de la Citadelle
  • Universitair Ziekenhuis Brussel
  • General Hospital Groeninge
Investigators  ICMJE
Principal Investigator: Marcel CG van de Poll, MD, PhD Maastricht UMC+
PRS Account Maastricht University Medical Center
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP