- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04633421
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
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
Enrollment (Anticipated)
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
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Belgium
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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
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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
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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]
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Noord-Brabant
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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
Accepts Healthy Volunteers
Genders Eligible for Study
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
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.
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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
Collaborators
Investigators
- Principal Investigator: Marcel CG van de Poll, MD, PhD, Maastricht UMC+
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
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
Studies a U.S. FDA-regulated device product
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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