PRotEin Provision in Critical IllneSs

Critical Illness Clinical Trial

— PRECISe  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04633421
• Other study ID #: NL73247.068.20
• Secondary ID: 80-85200-98-1857
• Status: Completed
• Phase: N/A
• Start date: November 19, 2020
• Est. completion date: October 3, 2023

Study information

• Verified date: January 2024
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 935
• Est. completion date: October 3, 2023
• Est. primary completion date: October 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Critical Illness
• Intensive Care Unit Acquired Weakness

Intervention

Dietary Supplement:
• PRECISe protocol EN 8g protein/100kcal
Enteral feed containing 8g protein/100kcal
• PRECISe protocol EN 5g protein/100kcal
Enteral feed containing 5g protein/100kcal

Locations

Country	Name	City	State
Belgium	UZ Brussel	Brussel
Belgium	Ziekenhuis Oost-Limburg	Genk
Belgium	AZ Groeninge	Kortrijk
Belgium	CHR de la Citadelle	Liège
Belgium	CHU Liège	Liège
Netherlands	Gelderse Vallei Ede	Ede
Netherlands	Catharina Ziekenhuis Eindhoven	Eindhoven	Noord-Brabant
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	Zuyderland Medisch Centrum	Heerlen
Netherlands	Maastricht Universtair Medisch Centrum	Maastricht

Sponsors (10)

Lead Sponsor	Collaborator
Maastricht University Medical Center	Catharina Ziekenhuis Eindhoven, Centre Hospitalier Régional de la Citadelle, Centre Hospitalier Universitaire de Liege, Gelderse Vallei Hospital, General Hospital Groeninge, Medisch Spectrum Twente, Universitair Ziekenhuis Brussel, Ziekenhuis Oost-Limburg, Zuyderland Medisch Centrum

Countries where clinical trial is conducted

Belgium,  Netherlands, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Duration of mechanical ventilation	Number of days on invasive mechanical ventilation.	During index ICU stay, up to 90 days.
Other	Duration of index ICU stay	Number of days in ICU.	During index ICU stay, up to 90 days.
Other	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.
Other	Hospital mortality	Hospital mortality	From index ICU admission until index hospital discharge, assessed up to 6 months.
Other	30-day mortality	Mortality at 30 days after ICU admission.	From index ICU admission until day 30.
Other	60-day mortality	Mortality at 60 days after ICU admission.	From index ICU admission until day 60.
Other	90-day mortality	Mortality at 90 days after ICU admission.	From index ICU admission until day 90.
Other	Time-to-discharge-alive	Days until live hospital discharge	From index ICU admission until index hospital discharge, assessed up to 6 months.
Other	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.
Other	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.
Other	Administration of prokinetics	Number of patients who received a prokinetic and number of days on it.	During index ICU stay, up to 90 days.
Other	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.
Other	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.
Other	Incidence of ICU-acquired infections	Number of patients who contracted an ICU-acquired infection.	During index ICU stay, up to 90 days.
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	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.
Other	Destination of hospital discharge	Destination of hospital discharge (home, rehabilitation center, care facility etc).	Follow-up until 180 days after index ICU admission.
Other	Length of stay at rehabilitation facility	Number of days at rehabilitation center.	Follow-up until 180 days after index ICU admission.
Other	Time to return to work	Number of days between ICU admission and return to work.	Follow-up until 180 days after index ICU admission.
Other	Health economic analysis	Total health care costs.	From index ICU admission until 180 days.
Primary	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.
Secondary	Overall survival	Overall survival	Day 30, 90 and 180 after ICU admission
Secondary	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.	Day 30, 90 and 180 after ICU admission
Secondary	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
Secondary	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
Secondary	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
Secondary	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.
Secondary	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
Secondary	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
Secondary	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.