The Effect of Higher Protein Dosing in Critically Ill Patients (EFFORT)

The Effect of Higher Protein Dosing in Critically Ill Patients: A Multicenter Registry-based Randomized Trial

The investigator will investigate the effects of higher protein/amino acid dosing (≥2.2 g/kg/d) vs usual protein/amino acid dosing (≤1.2 g/kg/d) on clinical outcomes in nutritionally high risk ill patients.

Study Overview

• Status: Completed
• Conditions: Critical Illness; Malnutrition
• Intervention / Treatment: Other: Usual Protein/Amino Acid Group; Other: Higher Protein/Amino Acid Group

Detailed Description

The EFFORT Study is a multi-center, pragmatic, volunteer-driven, registry-based, randomized, clinical trial of 4000 nutritionally high-risk critically ill patients in the intensive care unit (ICU). We anticipate over 100 sites participating internationally, with each site enrolling a minimum of 30 patients. Patients will be randomized to 1 of 2 treatment groups: a usual prescription (≤1.2 g/kg/d) or a higher prescription (≥2.2 g/kg/d) of protein. Other than the protein amount the patient is randomized to the remainder of care provided to randomized patient will be at the discretion of ICU providers.

In both groups, targets will be achieved through any combination of enteral nutrition (high protein content in high group if available), protein supplements, and parenteral nutrition or amino acids only (as clinically available). The only difference between the 2 groups is the protein targets that are set. Similar efforts should be used in both groups to achieve at least 80% of these targets. The remainder of care provided to eligible patients will be at the discretion of ICU providers.

The investigator has posed two research questions:

Primary Research Question:

In critically ill patients with nutrition 'risk factors', what is the effect of prescribing a higher dose (≥2.2 grams/kg/day) of protein/amino acid administration compared to a usual dose prescribed ≤1.2 gram/kg/day on time to discharge alive from hospital?

Secondary Research Question:

In critically ill patients with nutrition 'risk factors', what is the effect of prescribing a higher dose (≥2.2 grams/kg/day) of protein/amino acid administration compared to patients prescribed ≤1.2 gram/kg/day on 60 day mortality?

The proposed hypothesis:

Compared to receiving usual dose of protein/amino acids, the administration of a higher dose of protein/amino acids (a consequence of having a higher prescription) to nutritionally high-risk critically ill patients will be associated with a quicker rate of recovery and an improved survival.

• Study Type: Interventional
• Enrollment (Actual): 1329
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1280AEB CABA
    • Hospital Britanico de Buenos Aires
  • Cordoba, Argentina, 260
    • Sanatorio Allende
• Australia
  • Gold Coast, Australia
    • Gold Coast Hospital and Health Service
• Brazil
  • Rio de Janeiro, Brazil, 200
    • Casa de Saude Sao Jose
  • Rio de Janeiro, Brazil, 211
    • Hospital e Clínica São Gonçalo
  • Rio de Janeiro, Brazil, 222
    • Hospital Icarai
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, 869
      • Royal Alexandra Hospital
    • Edmonton, Alberta, Canada, 900
      • University of Alberta
  • British Columbia
    • Abbotsford, British Columbia, Canada
      • Abbotsford Regional Hospital
    • Burnaby, British Columbia, Canada
      • Burnaby Hospital
    • New Westminster, British Columbia, Canada
      • Royal Columbian Hospital
    • Surrey, British Columbia, Canada
      • Surrey Memorial Hospital
  • Ontario
    • London, Ontario, Canada
      • London Health Sciences Center Hospital
    • Owen Sound, Ontario, Canada, N4K 6M9
      • Grey Bruce Health Services
    • Toronto, Ontario, Canada, 442
      • Mount Sinai Hospital
  • Quebec
    • Montreal, Quebec, Canada, 547
      • CIUSSS de l'Est-de-l'ile-de-Montreal- Installation Hospital Maisonneuve-Rosemont
• Greece
  • Athens, Greece
    • Agioi Anargiroi Hospital
  • Athens, Greece
    • Evangelismos General Hospital
• Hong Kong
  • Hong Kong, Hong Kong, 1400
    • Queen Mary Hospital
• India
  • Mumbai, India
    • Apollo Hospitals Enterprises Limited
• Iran, Islamic Republic of
  • Mashhad, Iran, Islamic Republic of
    • Emam Reza Hospital, Mashhad University of Medical Science
• Japan
  • Hyogo
    • Kobe, Hyogo, Japan, 768
      • Kobe City Medical Center General Hospital
  • Midori-cho, Tachikawa-shi
    • Tokyo, Midori-cho, Tachikawa-shi, Japan, 3256
      • National Disaster Medical Center
• Malaysia
  • Kuala Lumpur, Malaysia
    • University of Malaya Medical Centre
• Mexico
  • Cdmx
    • Mexico City, Cdmx, Mexico, 298
      • Hospital General Dr. Manuel Gea González
  • Estado De Mexico
    • Mexico City, Estado De Mexico, Mexico, 165
      • Hospital Angeles Lomas
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44670
      • Hospital San Javier
    • Guadalajara, Jalisco, Mexico, 964
      • Hospital Civil Fray Antonio Alcalde
• Panama
  • Panamá, Panama, 200
    • Hospital Irma De Lourdes Tzanetatos
  • Panamá, Panama, 50
    • Complejo Hospitalario Dr. Arnulfo Arias Madrid de la Caja de Seguro Social
  • Chiriqui
    • David, Chiriqui, Panama, 330
      • Hospital Regional Rafael Hernandez L. David Chiriqui Css
• Puerto Rico
  • Caguas, Puerto Rico, 440
    • Hospital Himas San Pablo Caguas
• Saudi Arabia
  • Riyadh, Saudi Arabia
    • King Faisal Specialist Hospital and Research Center
• United Kingdom
  • Blackburn, United Kingdom
    • Royal Blackburn Hospital
  • Bristol, United Kingdom
    • North Bristol NHS Trust
  • Cambridge, United Kingdom
    • Addenbrooke's Hospital
  • Chichester, United Kingdom
    • St Richards Hospital
  • Cramlington, United Kingdom
    • Northumbria Emergency Care Hospital
  • Edinburgh, United Kingdom
    • Royal Infirmary of Edinburgh
  • Gateshead, United Kingdom
    • Queen Elizabeth Hospital
  • Gillingham, United Kingdom
    • Medway Maritime Hospital
  • Harrow, United Kingdom
    • Northwick Park Hospital
  • Ipswich, United Kingdom
    • East Suffolk & North Essex Foundation Trust
  • King's Lynn, United Kingdom
    • The Queen Elizabeth Hospital Kings Lynn NHS Trust
  • Llantrisant, United Kingdom
    • Royal Glamorgan Hospital
  • London, United Kingdom
    • Queen Elizabeth Hospital
  • London, United Kingdom
    • Royal Free London NHS Foundation Trust
  • London, United Kingdom
    • Guy's and St Thomas' NHS Foundation Trust
  • London, United Kingdom
    • Colchester Hospital
  • London, United Kingdom
    • Kings College Hospital Denmark Hill
  • London, United Kingdom
    • University Hospital Lewisham
  • Margate, United Kingdom
    • Queen Elizabeth the Queen Mother Hospital
  • Newcastle, United Kingdom
    • Freeman Hospital
  • Newport, United Kingdom
    • Aneurin Bevan University Health Board
  • Nottingham, United Kingdom
    • Nottingham University Hospitals Nhs Trust
  • Pembury, United Kingdom
    • The Tunbridge Wells Hospital
  • Portsmouth, United Kingdom
    • Queen Alexandra
  • Preston, United Kingdom
    • Royal Preston Hospital
  • Stevenage, United Kingdom
    • Lister Hospital East and North Hertfordshire Trust
  • Stoke-on-Trent, United Kingdom
    • Royal Stoke Hospital
  • Sunderland, United Kingdom
    • Sunderland Royal Hospital
  • Torquay, United Kingdom
    • Torbay Hospital
  • Worthing, United Kingdom
    • Worthing Hospital
  • Yeovil, United Kingdom
    • Yeovil District Hospital NHS Foundation Trust
  • Hampshire
    • Southampton, Hampshire, United Kingdom
      • University Southampton NHS Trust
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Phoenix VA Health Care System
    • Phoenix, Arizona, United States, 85006
      • Banner University Medical Center
  • California
    • Long Beach, California, United States, 90712
      • MemorialCare Long Beach Medical Center
  • Illinois
    • Evanston, Illinois, United States, 60077
      • Northshore University Healthsystem
    • Rockford, Illinois, United States, 61104
      • SwedishAmercian.Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • IU Health Methodist Hospital
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital and Medical Center
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Virtua
    • Mount Holly, New Jersey, United States, 28012
      • Virtua
    • Voorhees, New Jersey, United States, 08043
      • Virtua
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • OU Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania - MICU
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Center Knoxville
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22901
      • University of Virginia Health System
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Vancouver, Washington, United States, 98686
      • Legacy Salmon Creek Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Memorial Lutheran Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. ≥18 years old

2. Nutritionally 'high-risk' (meeting one of the below criteria)

   1. Low (≤25) or High BMI (≥35)
   2. Moderate to severe malnutrition (as defined by local assessments). We will document the means by which sites are making this determination and capture the elements of the assessment (history of weight loss, history of reduced oral intake, etc.).
   3. Frailty (Clinical Frailty Scale 5 or more from proxy)
   4. Sarcopenia- (SARC-F score of 4 or more from proxy)
   5. From point of screening, projected duration of mechanical ventilation >4 days
3. Requiring mechanical ventilation with actual or expected total duration of mechanical ventilation >48 hours

Exclusion Criteria:

1. >96 continuous hours of mechanical ventilation before screening
2. Expected death or withdrawal of life-sustaining treatments within 7 days from screening
3. Pregnant
4. The responsible clinician feels that the patient either needs low or high protein
5. Patient requires parenteral nutrition only and site does not have products to reach the high protein dose group.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Usual Protein/Amino Acid Group; Patients will receive a usual protein/amino acid dose (≤1.2 g/kg/d)	Other: Usual Protein/Amino Acid Group; Protein targets will be set using pre-ICU dry actual weight. For patients with BMI >30, ideal body weight based on a BMI of 25 will be used. We will endorse the guidelines for energy targets set forth by ASPEN/SCCM, especially as it pertains to the obese patient.
Active Comparator: Higher Protein/Amino Acid Group; Patients will receive a higher protein/amino acid dose (≥2.2 g/kg/d).	Other: Higher Protein/Amino Acid Group; Protein targets will be set using pre-ICU dry actual weight. For patients with BMI >30, ideal body weight based on a BMI of 25 will be used. We will endorse the guidelines for energy targets set forth by ASPEN/SCCM, especially as it pertains to the obese patient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to discharge alive from hospital	This is a composite of mortality and length of stay, evaluated up to 60 days post randomization	60 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
60-day mortality	Mortality 60 days post randomization	60 day

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nutritional Adequacy	To be evaluated up to 60 days post randomization	60 day
Hospital mortality	To be evaluated up to 60 days post randomization	60 day
Readmission to ICU and Hospital	To be evaluated up to 60 days post randomization	60 day
Duration of Mechanical Ventilation	To be evaluated up to 60 days post randomization	60 day
ICU length of stay	To be evaluated up to 60 days post randomization	60 day
Hospital length of stay	To be evaluated up to 60 days post randomization	60 day

Collaborators and Investigators

• Sponsor: Clinical Evaluation Research Unit at Kingston General Hospital

Publications and helpful links

General Publications

• De Jonghe B, Sharshar T, Lefaucheur JP, Authier FJ, Durand-Zaleski I, Boussarsar M, Cerf C, Renaud E, Mesrati F, Carlet J, Raphael JC, Outin H, Bastuji-Garin S; Groupe de Reflexion et d'Etude des Neuromyopathies en Reanimation. Paresis acquired in the intensive care unit: a prospective multicenter study. JAMA. 2002 Dec 11;288(22):2859-67. doi: 10.1001/jama.288.22.2859.
• Heyland DK, Cahill N, Day AG. Optimal amount of calories for critically ill patients: depends on how you slice the cake! Crit Care Med. 2011 Dec;39(12):2619-26. doi: 10.1097/CCM.0b013e318226641d.
• Hermans G, Van Mechelen H, Clerckx B, Vanhullebusch T, Mesotten D, Wilmer A, Casaer MP, Meersseman P, Debaveye Y, Van Cromphaut S, Wouters PJ, Gosselink R, Van den Berghe G. Acute outcomes and 1-year mortality of intensive care unit-acquired weakness. A cohort study and propensity-matched analysis. Am J Respir Crit Care Med. 2014 Aug 15;190(4):410-20. doi: 10.1164/rccm.201312-2257OC.
• Fan E, Dowdy DW, Colantuoni E, Mendez-Tellez PA, Sevransky JE, Shanholtz C, Himmelfarb CR, Desai SV, Ciesla N, Herridge MS, Pronovost PJ, Needham DM. Physical complications in acute lung injury survivors: a two-year longitudinal prospective study. Crit Care Med. 2014 Apr;42(4):849-59. doi: 10.1097/CCM.0000000000000040.
• Jolly SS, Cairns JA, Yusuf S, Meeks B, Pogue J, Rokoss MJ, Kedev S, Thabane L, Stankovic G, Moreno R, Gershlick A, Chowdhary S, Lavi S, Niemela K, Steg PG, Bernat I, Xu Y, Cantor WJ, Overgaard CB, Naber CK, Cheema AN, Welsh RC, Bertrand OF, Avezum A, Bhindi R, Pancholy S, Rao SV, Natarajan MK, ten Berg JM, Shestakovska O, Gao P, Widimsky P, Dzavik V; TOTAL Investigators. Randomized trial of primary PCI with or without routine manual thrombectomy. N Engl J Med. 2015 Apr 9;372(15):1389-98. doi: 10.1056/NEJMoa1415098. Epub 2015 Mar 16.
• Hoffer LJ, Bistrian BR. Appropriate protein provision in critical illness: a systematic and narrative review. Am J Clin Nutr. 2012 Sep;96(3):591-600. doi: 10.3945/ajcn.111.032078. Epub 2012 Jul 18.
• Hill A, Heyland DK, Elke G, Schaller SJ, Stocker R, Haberthur C, von Loeffelholz C, Suchner U, Puthucheary ZA, Bear DE, Ney J, Clasen KC, Meybohm P, Lindau S, Laurentius T, Stoppe C. Meeting nutritional targets of critically ill patients by combined enteral and parenteral nutrition: review and rationale for the EFFORTcombo trial. Nutr Res Rev. 2020 Dec;33(2):312-320. doi: 10.1017/S0954422420000165. Epub 2020 Jul 16.

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2017
• Primary Completion (Actual): December 3, 2021
• Study Completion (Actual): December 3, 2021

Study Registration Dates

• First Submitted: May 17, 2017
• First Submitted That Met QC Criteria: May 17, 2017
• First Posted (Actual): May 19, 2017

Study Record Updates

• Last Update Posted (Actual): March 28, 2022
• Last Update Submitted That Met QC Criteria: March 25, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Nutrition Disorders; Critical Illness; Malnutrition
• Other Study ID Numbers: The EFFORT Trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No