PRotEin Provision in Critical IllneSs

Conditions

Critical Illness, Intensive Care Unit Acquired Weakness

Keywords

Enteral Nutrition, Dietary Proteins, Respiratory failure, Catabolism

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 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.

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.

Schouteden E, Heuts S, Bels JL, Thiesen S, van Gassel RJ, Lee ZY, Stoppe C, Beishuizen A, De Bie Dekker A, Fraipont V, Lamote S, Ledoux D, Scheeren C, De Waele E, van Zanten A, van Kuijk SM, van de Poll MC, Mesotten D, Gabrio A, PRECISe study team.

2025-04-012 citations

10.1016/j.clnu.2025.03.022

Effect of high versus standard protein provision on functional recovery in people with critical illness (PRECISe): an investigator-initiated, double-blinded, multicentre, parallel-group, randomised controlled trial in Belgium and the Netherlands.

Bels JLM, Thiessen S, van Gassel RJJ, Beishuizen A, De Bie Dekker A, Fraipont V, Lamote S, Ledoux D, Scheeren C, De Waele E, van Zanten ARH, Bormans-Russell L, van Bussel BCT, Dictus MMJ, Fivez T, Harks I, van der Horst ICC, Jonckheer J, Marechal H, Massion PB, Meex I, Paulus MC, Rinket M, van Santen S, Tartaglia K, Deane AM, Demuydt F, Puthucheary Z, Vloet LCM, Weijs PJM, van Kuijk SMJ, van de Poll MCG, Mesotten D, PRECISe study team.

2024-08-0164 citations

10.1016/s0140-6736(24)01304-7

The impact of high versus standard enteral protein provision on functional recovery following intensive care admission (PRECISE trial): study protocol for a randomized controlled, quadruple blinded, multicenter, parallel group trial in mechanically ventilated patients.

van Gassel RJJ, Bels JLM, Tartaglia K, van Bussel BCT, van Kuijk SMJ, Deane AM, Puthucheary Z, Weijs PJM, Vloet L, Beishuizen B, De Bie Dekker A, Fraipont V, Lamote S, Ledoux D, Scheeren C, De Waele E, van Zanten ARH, Mesotten D, van de Poll MCG.

2023-06-199 citations

10.1186/s13063-023-07380-3

Interventions

DIETARY_SUPPLEMENTPRECISe protocol EN 8g protein/100kcal

Enteral feed containing 8g protein/100kcal

DIETARY_SUPPLEMENTPRECISe protocol EN 5g protein/100kcal

Enteral feed containing 5g protein/100kcal

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, 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.

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame	Description
Health Related Quality of Life (HRQL)	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

Measure	Time frame	Description
Mental health status - post-traumatic stress	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.
Muscle and nerve function - handgrip strength	Day 30, 90 and 180 after ICU admission.	Handgrip strength, assessed via a hand dynamometer and measured in kilograms (kg).
Overall survival	Day 30, 90 and 180 after ICU admission	Overall survival
Health-related Quality of Life - SF-36	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.
Muscle and nerve function - MRC-sum score	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.
Physical function - 6-minute walk test	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.
Pain intensity	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	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 - anxiety/depression	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.

Other

Measure	Time frame	Description
Administration of prokinetics	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	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.
Incidence of ICU-readmission	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	During index ICU stay, up to 90 days.	Number of patients who contracted an ICU-acquired infection.
Incidence of acute kidney injury	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	During index ICU stay, up to 90 days.	Number of patients who received renal replacement therapy and days on it.
Incidence of hepatic dysfunction	During index ICU stay, up to 90 days.	Number of patients with hepatic dysfunction, defined as a total bilirubin level \> 3mg/dL.
Duration of mechanical ventilation	During index ICU stay, up to 90 days.	Number of days on invasive mechanical ventilation.
Difference in mobilization treatment	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	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.
Domain data EQ-5D	Day 30, 90 and 180 after ICU admission.	Scores of subdomains of EQ-5D, ranging from 1 to 5. A higher score indicates a higher severity level on that subdomain.
Destination of hospital discharge	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	Follow-up until 180 days after index ICU admission.	Number of days at rehabilitation center.
Time to return to work	Follow-up until 180 days after index ICU admission.	Number of days between ICU admission and return to work.
Health economic analysis	From index ICU admission until 180 days.	Total health care costs.
Maximum and mean SOFA score	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.
Duration of index ICU stay	During index ICU stay, up to 90 days.	Number of days in ICU.
Duration of index hospital stay	From date of randomization until the date of index hospital discharge, assessed up to 6 months.	Number of days in hospital.
Hospital mortality	From index ICU admission until index hospital discharge, assessed up to 6 months.	Hospital mortality
30-day mortality	From index ICU admission until day 30.	Mortality at 30 days after ICU admission.
60-day mortality	From index ICU admission until day 60.	Mortality at 60 days after ICU admission.
90-day mortality	From index ICU admission until day 90.	Mortality at 90 days after ICU admission.
Time-to-discharge-alive	From index ICU admission until index hospital discharge, assessed up to 6 months.	Days until live hospital discharge
Days alive and at home at day 90	From index ICU admission until day 90.	Number of days alive and at home at day 90 after ICU admission.
Nutritional adequacy	From index ICU admission until index ICU discharge, assessed up to 6 months.	Ratio between total amount of calories and grams of protein actually received by patients and prescribed during treatment period.

Countries

Belgium, Netherlands

Outcome results

None listed