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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 Liege
Centre Hospitalier Régional de la Citadelle
Universitair Ziekenhuis Brussel
General Hospital Groeninge
Information provided by (Responsible Party):
Maastricht University Medical Center

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.


Condition or disease Intervention/treatment Phase
Critical Illness Intensive Care Unit Acquired Weakness Dietary Supplement: PRECISe protocol EN 8g protein/100kcal Dietary Supplement: PRECISe protocol EN 5g protein/100kcal Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 824 participants
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
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
Actual Study Start Date : November 19, 2020
Estimated Primary Completion Date : May 2023
Estimated Study Completion Date : May 2023

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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: Day 30, 90 and 180 after ICU admission ]
    Overall survival

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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).


Other Outcome Measures:
  1. 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.

  2. 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.

  3. Duration of mechanical ventilation [ Time Frame: During index ICU stay, up to 90 days. ]
    Number of days on invasive mechanical ventilation.

  4. Duration of index ICU stay [ Time Frame: During index ICU stay, up to 90 days. ]
    Number of days in ICU.

  5. 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.

  6. 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.

  7. Incidence of ICU-acquired infections [ Time Frame: During index ICU stay, up to 90 days. ]
    Number of patients who contracted an ICU-acquired infection.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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).

  13. 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.

  14. 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).

  15. Length of stay at rehabilitation facility [ Time Frame: Follow-up until 180 days after index ICU admission. ]
    Number of days at rehabilitation center.

  16. 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.

  17. Health economic analysis [ Time Frame: From index ICU admission until 180 days. ]
    Total health care costs.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04633421


Contacts
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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

Locations
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Belgium
UZ Brussel Recruiting
Brussel, Belgium
Contact: Elisabeth de Waele, MD, PhD         
Ziekenhuis Oost-Limburg Recruiting
Genk, Belgium, 3600
Contact: Dieter Mesotten       precise@zol.be   
Contact: Katrien Tartaglia       precise@zol.be   
AZ Groeninge Recruiting
Kortrijk, Belgium
Contact: Stoffel Lamote, MD, PhD         
CHR de la Citadelle Recruiting
Liège, Belgium
Contact: Vincent Fraipont, MD, PhD         
CHU Liège Recruiting
Liège, Belgium
Contact: Didier Ledoux, MD, PhD         
Netherlands
Gelderse Vallei Ede Recruiting
Ede, Netherlands
Contact: Arthur van Zanten, MD, PhD         
Medisch Spectrum Twente Recruiting
Enschede, Netherlands
Contact: Bert Beishuizen, MD, PhD         
Zuyderland Medisch Centrum Recruiting
Heerlen, Netherlands
Contact: Clarissa Scheeren, MD         
Maastricht Universtair Medisch Centrum Recruiting
Maastricht, Netherlands
Contact: Marcel van de Poll, MD, PhD         
Contact: Julia Bels, MD    +31 (0) 6 30 48 06 85    precise@mumc.nl   
Sponsors and Collaborators
Maastricht University Medical Center
Ziekenhuis Oost-Limburg
Zuyderland Medisch Centrum
Gelderse Vallei Hospital
Medisch Spectrum Twente
Centre Hospitalier Universitaire de Liege
Centre Hospitalier Régional de la Citadelle
Universitair Ziekenhuis Brussel
General Hospital Groeninge
Investigators
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Principal Investigator: Marcel CG van de Poll, MD, PhD Maastricht UMC+
Publications:
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Responsible Party: Maastricht University Medical Center
ClinicalTrials.gov Identifier: NCT04633421    
Other Study ID Numbers: NL73247.068.20
80-85200-98-18574 ( Other Grant/Funding Number: KCE-ZonMW (BeNeFIT) )
First Posted: November 18, 2020    Key Record Dates
Last Update Posted: March 24, 2021
Last Verified: March 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Maastricht University Medical Center:
Enteral Nutrition
Dietary Proteins
Respiratory failure
Catabolism
Additional relevant MeSH terms:
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Critical Illness
Disease Attributes
Pathologic Processes