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| ID | Type | Description | Link |
|---|---|---|---|
| 80-85200-98-18574 | Other Grant/Funding Number | KCE-ZonMW (BeNeFIT) |
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| Name | Class |
|---|---|
| Ziekenhuis Oost-Limburg | OTHER |
| Zuyderland Medisch Centrum | OTHER |
| Gelderse Vallei Hospital | OTHER |
| Medisch Spectrum Twente |
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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.
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PRECISe protocol EN (8g protein/100kcal) | Experimental | 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. |
|
| PRECISe protocol EN (5g protein/100kcal) | Active Comparator | Enteral (EN) feed with 5 grams protein per 100 kcal (1.3 g/kg/day protein when on target). The caloric goal is 25 kcal/kg/day to be reached on day 4 of ICU admission. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PRECISe protocol EN 8g protein/100kcal | Dietary Supplement | Enteral feed containing 8g protein/100kcal |
|
| Measure | Description | Time Frame |
|---|---|---|
| Health Related Quality of Life (HRQL) | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival | Overall survival | Day 30, 90 and 180 after ICU admission |
| Health-related Quality of Life - SF-36 | Short Form 36 (SF-36), ranging from 0 to 100. A higher score indicates a better Health-related Quality of Life. |
| Measure | Description | Time Frame |
|---|---|---|
| Duration of mechanical ventilation | Number of days on invasive mechanical ventilation. | During index ICU stay, up to 90 days. |
| Duration of index ICU stay | Number of days in ICU. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marcel CG van de Poll, MD, PhD | Maastricht UMC | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UZ Brussel | Brussels | Belgium | ||||
| Ziekenhuis Oost-Limburg |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28537429 | Background | 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. | |
| 40215884 | Derived |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Mar 20, 2025 | |
| Reset | Apr 7, 2025 |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 30, 2023 | Jan 14, 2024 | SAP_000.pdf |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Mar 20, 2025 | Apr 7, 2025 |
| ID | Term |
|---|---|
| D016638 | Critical Illness |
| D012131 | Respiratory Insufficiency |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012120 | Respiration Disorders |
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| ID | Term |
|---|---|
| D011506 | Proteins |
| ID | Term |
|---|---|
| D000602 | Amino Acids, Peptides, and Proteins |
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| OTHER |
| Centre Hospitalier Universitaire de Liege | OTHER |
| Centre Hospitalier Régional de la Citadelle | OTHER |
| Universitair Ziekenhuis Brussel | OTHER |
| General Hospital Groeninge | OTHER |
| Catharina Ziekenhuis Eindhoven | OTHER |
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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.
| PRECISe protocol EN 5g protein/100kcal | Dietary Supplement | Enteral feed containing 5g protein/100kcal |
|
| Day 30, 90 and 180 after ICU admission |
| Mental health status - anxiety/depression | 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 | 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 | 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 | 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 | 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 | 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 | Handgrip strength, assessed via a hand dynamometer and measured in kilograms (kg). | Day 30, 90 and 180 after ICU admission. |
| During index ICU stay, up to 90 days. |
| Duration of index hospital stay | Number of days in hospital. | From date of randomization until the date of index hospital discharge, assessed up to 6 months. |
| Hospital mortality | Hospital mortality | From index ICU admission until index hospital discharge, assessed up to 6 months. |
| 30-day mortality | Mortality at 30 days after ICU admission. | From index ICU admission until day 30. |
| 60-day mortality | Mortality at 60 days after ICU admission. | From index ICU admission until day 60. |
| 90-day mortality | Mortality at 90 days after ICU admission. | From index ICU admission until day 90. |
| Time-to-discharge-alive | Days until live hospital discharge | From index ICU admission until index hospital discharge, assessed up to 6 months. |
| Days alive and at home at day 90 | Number of days alive and at home at day 90 after ICU admission. | From index ICU admission until day 90. |
| Nutritional adequacy | Ratio between total amount of calories and grams of protein actually received by patients and prescribed during treatment period. | From index ICU admission until index ICU discharge, assessed up to 6 months. |
| Administration of prokinetics | 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 | 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. |
| Incidence of ICU-readmission | 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 | Number of patients who contracted an ICU-acquired infection. | During index ICU stay, up to 90 days. |
| Incidence of acute kidney injury | 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 | Number of patients who received renal replacement therapy and days on it. | During index ICU stay, up to 90 days. |
| Incidence of hepatic dysfunction | 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 | 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 | 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 | 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. |
| Domain data EQ-5D | Scores of subdomains of EQ-5D, ranging from 1 to 5. A higher score indicates a higher severity level on that subdomain. | Day 30, 90 and 180 after ICU admission. |
| Destination of hospital discharge | 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 | Number of days at rehabilitation center. | Follow-up until 180 days after index ICU admission. |
| Time to return to work | Number of days between ICU admission and return to work. | Follow-up until 180 days after index ICU admission. |
| Health economic analysis | Total health care costs. | From index ICU admission until 180 days. |
| Genk |
| 3600 |
| Belgium |
| AZ Groeninge | Kortrijk | Belgium |
| CHR de la Citadelle | Liège | Belgium |
| CHU Liège | Liège | Belgium |
| Catharina Ziekenhuis Eindhoven | Eindhoven | North Brabant | 5623 EJ | Netherlands |
| Gelderse Vallei Ede | Ede | Netherlands |
| Medisch Spectrum Twente | Enschede | Netherlands |
| Zuyderland Medisch Centrum | Heerlen | Netherlands |
| Maastricht Universtair Medisch Centrum | Maastricht | Netherlands |
| 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. The impact of high versus standard enteral protein provision on functional recovery following intensive care admission: A pre-planned Bayesian analysis of the PRECISe trial. Clin Nutr. 2025 May;48:153-160. doi: 10.1016/j.clnu.2025.03.022. Epub 2025 Apr 1. |
| 39153816 | Derived | 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. 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. Lancet. 2024 Aug 17;404(10453):659-669. doi: 10.1016/S0140-6736(24)01304-7. |
| 37337234 | Derived | 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. 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. Trials. 2023 Jun 19;24(1):416. doi: 10.1186/s13063-023-07380-3. |
| D012140 | Respiratory Tract Diseases |