PRECISe: PRotEin Provision in Critical IllneSs
Study Details
Study Description
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 |
|---|---|---|
|
N/A |
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 Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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.
- 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 - 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.
- 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.
- 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.
- 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).
Other Outcome Measures
- 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.
- Duration of mechanical ventilation [During index ICU stay, up to 90 days.]
Number of days on invasive mechanical ventilation.
- 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.
- 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.
- 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.
- 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.
- 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.
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UZ Brussel | Brussel | Belgium | ||
| 2 | Ziekenhuis Oost-Limburg | Genk | Belgium | 3600 | |
| 3 | AZ Groeninge | Kortrijk | Belgium | ||
| 4 | CHR de la Citadelle | Liège | Belgium | ||
| 5 | CHU Liège | Liège | Belgium | ||
| 6 | Gelderse Vallei Ede | Ede | Netherlands | ||
| 7 | Medisch Spectrum Twente | Enschede | Netherlands | ||
| 8 | Zuyderland Medisch Centrum | Heerlen | Netherlands | ||
| 9 | Maastricht Universtair Medisch Centrum | Maastricht | Netherlands |
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
- Principal Investigator: Marcel CG van de Poll, MD, PhD, Maastricht UMC+
Study Documents (Full-Text)
None provided.More Information
Publications
- NL73247.068.20
- 80-85200-98-18574