PRotEin Provision in Critical IllneSs

NCT ID: NCT04633421

Last Updated: 2024-01-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 935 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-19
• Study Completion Date: 2023-10-03

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.

Conditions

Critical Illness; Intensive Care Unit Acquired Weakness

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

PRECISe protocol EN 8g protein/100kcal

Intervention Type: DIETARY_SUPPLEMENT

Enteral feed containing 8g protein/100kcal

PRECISe protocol EN (5g protein/100kcal)

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.

Group Type: ACTIVE_COMPARATOR

PRECISe protocol EN 5g protein/100kcal

Intervention Type: DIETARY_SUPPLEMENT

Enteral feed containing 5g protein/100kcal

Interventions

PRECISe protocol EN 8g protein/100kcal

Enteral feed containing 8g protein/100kcal

Intervention Type: DIETARY_SUPPLEMENT

PRECISe protocol EN 5g protein/100kcal

Enteral feed containing 5g protein/100kcal

Intervention Type: DIETARY_SUPPLEMENT

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ziekenhuis Oost-Limburg

OTHER

Sponsor Role: collaborator

Zuyderland Medisch Centrum

OTHER

Sponsor Role: collaborator

Gelderse Vallei Hospital

OTHER

Sponsor Role: collaborator

Medisch Spectrum Twente

OTHER

Sponsor Role: collaborator

Centre Hospitalier Universitaire de Liege

OTHER

Sponsor Role: collaborator

Centre Hospitalier Régional de la Citadelle

OTHER

Sponsor Role: collaborator

Universitair Ziekenhuis Brussel

OTHER

Sponsor Role: collaborator

General Hospital Groeninge

OTHER

Sponsor Role: collaborator

Catharina Ziekenhuis Eindhoven

OTHER

Sponsor Role: collaborator

Maastricht University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marcel CG van de Poll, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Maastricht UMC+

Locations

UZ Brussel

Brussels, , Belgium

Ziekenhuis Oost-Limburg

Genk, , Belgium

AZ Groeninge

Kortrijk, , Belgium

CHR de la Citadelle

Liège, , Belgium

CHU Liège

Liège, , Belgium

Catharina Ziekenhuis Eindhoven

Eindhoven, North Brabant, Netherlands

Gelderse Vallei Ede

Ede, , Netherlands

Medisch Spectrum Twente

Enschede, , Netherlands

Zuyderland Medisch Centrum

Heerlen, , Netherlands

Maastricht Universtair Medisch Centrum

Maastricht, , Netherlands

Countries

Belgium; Netherlands

References

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.

Reference Type: BACKGROUND

PMID: 28537429 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 40215884 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39153816 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37337234 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

80-85200-98-18574

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

NL73247.068.20

Identifier Type: -

Identifier Source: org_study_id