The Effect of Higher Protein Dosing in Critically Ill Patients

NCT03160547 | Completed DMC

• 1 other identifier: The EFFORT Trial
• Study Type: interventional
• Target: 1,329
• Locations: 16 countries
• Sites: 86

Brief Summary

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.

Conditions

Critical Illness; Malnutrition

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• 60-day mortality

  60 day

Other Outcomes (6)

• Nutritional Adequacy

  60 day

• Hospital mortality

  60 day

• Readmission to ICU and Hospital

  60 day

Study Arms (2)

Usual Protein/Amino Acid Group

ACTIVE COMPARATOR

Patients will receive a usual protein/amino acid dose (≤1.2 g/kg/d)

Other: Usual Protein/Amino Acid Group

Higher Protein/Amino Acid Group

ACTIVE COMPARATOR

Patients will receive a higher protein/amino acid dose (≥2.2 g/kg/d).

Other: Higher Protein/Amino Acid Group

Interventions

Usual Protein/Amino Acid Group OTHER

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.

Usual Protein/Amino Acid Group

Higher Protein/Amino Acid Group OTHER

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.

Higher Protein/Amino Acid Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years old
• Nutritionally 'high-risk' (meeting one of the below criteria)
• Low (≤25) or High BMI (≥35)
• 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.).
• Frailty (Clinical Frailty Scale 5 or more from proxy)
• Sarcopenia- (SARC-F score of 4 or more from proxy)
• From point of screening, projected duration of mechanical ventilation \>4 days
• Requiring mechanical ventilation with actual or expected total duration of mechanical ventilation \>48 hours

You may not qualify if:

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

Sponsors & Collaborators

• Clinical Evaluation Research Unit at Kingston General Hospital: lead

Study Sites (86)

Banner University Medical Center

Phoenix, Arizona, 85006, United States

Location

Phoenix VA Health Care System

Phoenix, Arizona, 85012, United States

Location

MemorialCare Long Beach Medical Center

Long Beach, California, 90712, United States

Location

NorthShore University HealthSystem

Evanston, Illinois, 60077, United States

Location

SwedishAmercian.Hospital

Rockford, Illinois, 61104, United States

Location

IU Health Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

Lahey Hospital and Medical Center

Burlington, Massachusetts, 01805, United States

Location

Spectrum Health

Grand Rapids, Michigan, 49503, United States

Location

Virtua

Marlton, New Jersey, 08053, United States

Location

Virtua

Mount Holly, New Jersey, 28012, United States

Location

Virtua

Voorhees Township, New Jersey, 08043, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Fairfield Medical Center

Lancaster, Ohio, 43130, United States

Location

OU Medical Center

Oklahoma City, Oklahoma, 73104, United States

Location

Hospital of the University of Pennsylvania - MICU

Philadelphia, Pennsylvania, 19104, United States

Location

University of Tennessee Medical Center Knoxville

Knoxville, Tennessee, 37920, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22901, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Legacy Salmon Creek Medical Center

Vancouver, Washington, 98686, United States

Location

Froedtert Memorial Lutheran Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Hospital Britanico de Buenos Aires

Buenos Aires, C1280AEB CABA, Argentina

Location

Sanatorio Allende

Córdoba, 260, Argentina

Location

Gold Coast Hospital and Health Service

Gold Coast, Australia

Location

Casa de Saude Sao Jose

Rio de Janeiro, 200, Brazil

Location

Hospital e Clinica Sao Goncalo

Rio de Janeiro, 211, Brazil

Location

Hospital Icarai

Rio de Janeiro, 222, Brazil

Location

Royal Alexandra Hospital

Edmonton, Alberta, 869, Canada

Location

University of Alberta

Edmonton, Alberta, 900, Canada

Location

Abbotsford Regional Hospital

Abbotsford, British Columbia, Canada

Location

Burnaby Hospital

Burnaby, British Columbia, Canada

Location

Royal Columbian Hospital

New Westminster, British Columbia, Canada

Location

Surrey Memorial Hospital

Surrey, British Columbia, Canada

Location

London Health Sciences Center Hospital

London, Ontario, Canada

Location

Grey Bruce Health Services

Owen Sound, Ontario, N4K 6M9, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, 442, Canada

Location

CIUSSS de l'Est-de-l'ile-de-Montreal- Installation Hospital Maisonneuve-Rosemont

Montreal, Quebec, 547, Canada

Location

Agioi Anargiroi Hospital

Athens, Greece

Location

Evangelismos General Hospital

Athens, Greece

Location

Queen Mary Hospital

Hong Kong, 1400, Hong Kong

Location

Apollo Hospitals Enterprises Limited

Mumbai, India

Location

Emam Reza Hospital, Mashhad University of Medical Science

Mashhad, Iran

Location

Kobe City Medical Center General Hospital

Kobe, Hyōgo, 768, Japan

Location

National Disaster Medical Center

Tokyo, Midori-cho, Tachikawa-shi, 3256, Japan

Location

University of Malaya Medical Centre

Kuala Lumpur, Malaysia

Location

Hospital San Javier

Guadalajara, Jalisco, 44670, Mexico

Location

Hospital Civil Fray Antonio Alcalde

Guadalajara, Jalisco, 964, Mexico

Location

Hospital General Dr. Manuel Gea Gonzalez

Mexico City, Mexico City, 298, Mexico

Location

Hospital Angeles Lomas

México, State of Mexico, 165, Mexico

Location

Hospital Regional Rafael Hernandez L. David Chiriqui Css

David, Chiriquí Province, 330, Panama

Location

Hospital Irma De Lourdes Tzanetatos

Panama City, 200, Panama

Location

Complejo Hospitalario Dr. Arnulfo Arias Madrid de la Caja de Seguro Social

Panama City, 50, Panama

Location

Hospital Himas San Pablo Caguas

Caguas, 440, Puerto Rico

Location

King Faisal Specialist Hospital and Research Center

Riyadh, Saudi Arabia

Location

University Southampton NHS Trust

Southampton, Hampshire, United Kingdom

Location

Royal Blackburn Hospital

Blackburn, United Kingdom

Location

North Bristol NHS Trust

Bristol, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, United Kingdom

Location

St Richards Hospital

Chichester, United Kingdom

Location

Northumbria Emergency Care Hospital

Cramlington, United Kingdom

Location

Royal Infirmary of Edinburgh

Edinburgh, United Kingdom

Location

Queen Elizabeth Hospital

Gateshead, United Kingdom

Location

Medway Maritime Hospital

Gillingham, United Kingdom

Location

Northwick Park hospital

Harrow, United Kingdom

Location

East Suffolk & North Essex Foundation Trust

Ipswich, United Kingdom

Location

The Queen Elizabeth Hospital Kings Lynn NHS Trust

Kings Lynn, United Kingdom

Location

Royal Glamorgan Hospital

Llantrisant, United Kingdom

Location

Colchester Hospital

London, United Kingdom

Location

Guy's and St Thomas' NHS Foundation Trust

London, United Kingdom

Location

Kings College Hospital Denmark Hill

London, United Kingdom

Location

Queen Elizabeth Hospital

London, United Kingdom

Location

Royal Free London NHS Foundation Trust

London, United Kingdom

Location

University Hospital Lewisham

London, United Kingdom

Location

Queen Elizabeth the Queen Mother Hospital

Margate, United Kingdom

Location

Freeman Hospital

Newcastle, United Kingdom

Location

Aneurin bevan University Health Board

Newport, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, United Kingdom

Location

The Tunbridge Wells Hospital

Pembury, United Kingdom

Location

Queen Alexandra

Portsmouth, United Kingdom

Location

Royal Preston Hospital

Preston, United Kingdom

Location

Lister Hospital East and North Hertfordshire Trust

Stevenage, United Kingdom

Location

Royal Stoke Hospital

Stoke-on-Trent, United Kingdom

Location

Sunderland Royal Hospital

Sunderland, United Kingdom

Location

Torbay Hospital

Torquay, United Kingdom

Location

Worthing Hospital

Worthing, United Kingdom

Location

Yeovil District Hospital NHS Foundation Trust

Yeovil, United Kingdom

Location

Related Publications (13)

• 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.

  PMID: 22811443 BACKGROUND

• 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.

  PMID: 21705881 BACKGROUND

• 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.

  PMID: 25853743 BACKGROUND

• 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.

  PMID: 24247473 BACKGROUND

• 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.

  PMID: 12472328 BACKGROUND

• 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.

  PMID: 24825371 BACKGROUND

• Tweel LE, Brody R, Samavat H, Day AG, Jiang X, Byham-Gray L, Patel J, Compher C, Heyland DK. Association between protein dose in the early and late acute phases of critical illness and time-to-discharge-alive: A secondary analysis of a randomized clinical trial. JPEN J Parenter Enteral Nutr. 2025 Nov 14. doi: 10.1002/jpen.70033. Online ahead of print.

  PMID: 41236842 DERIVED

• Lew CCH, Lee ZY, Day AG, Jiang X, Bear D, Jensen GL, Ng PY, Tweel L, Parillo A, Heyland DK, Compher C. The Association Between Malnutrition and High Protein Treatment on Outcomes in Critically Ill Patients: A Post Hoc Analysis of the EFFORT Protein Randomized Trial. Chest. 2024 Jun;165(6):1380-1391. doi: 10.1016/j.chest.2024.02.008. Epub 2024 Feb 12.

  PMID: 38354904 DERIVED

• Haines RW, Prowle JR, Day A, Bear DE, Heyland DK, Puthucheary Z. Association between urea trajectory and protein dose in critically ill adults: a secondary exploratory analysis of the effort protein trial (RE-EFFORT). Crit Care. 2024 Jan 16;28(1):24. doi: 10.1186/s13054-024-04799-1.

  PMID: 38229072 DERIVED

• Tweel LE, Compher C, Bear DE, Gutierrez-Castrellon P, Leaver SK, MacEachern K, Ortiz-Reyes L, Pooja L, Leon A, Wedemire C, Lee ZY, Day AG, Heyland DK. A Comparison of High and Usual Protein Dosing in Critically Ill Patients With Obesity: A Post Hoc Analysis of an International, Pragmatic, Single-Blinded, Randomized Clinical Trial. Crit Care Med. 2024 Apr 1;52(4):586-595. doi: 10.1097/CCM.0000000000006117. Epub 2023 Nov 6.

  PMID: 37930244 DERIVED

• Stoppe C, Patel JJ, Zarbock A, Lee ZY, Rice TW, Mafrici B, Wehner R, Chan MHM, Lai PCK, MacEachern K, Myrianthefs P, Tsigou E, Ortiz-Reyes L, Jiang X, Day AG, Hasan MS, Meybohm P, Ke L, Heyland DK. The impact of higher protein dosing on outcomes in critically ill patients with acute kidney injury: a post hoc analysis of the EFFORT protein trial. Crit Care. 2023 Oct 18;27(1):399. doi: 10.1186/s13054-023-04663-8.

  PMID: 37853490 DERIVED

• Heyland DK, Patel J, Compher C, Rice TW, Bear DE, Lee ZY, Gonzalez VC, O'Reilly K, Regala R, Wedemire C, Ibarra-Estrada M, Stoppe C, Ortiz-Reyes L, Jiang X, Day AG; EFFORT Protein Trial team. The effect of higher protein dosing in critically ill patients with high nutritional risk (EFFORT Protein): an international, multicentre, pragmatic, registry-based randomised trial. Lancet. 2023 Feb 18;401(10376):568-576. doi: 10.1016/S0140-6736(22)02469-2. Epub 2023 Jan 25.

  PMID: 36708732 DERIVED

• 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.

  PMID: 32669140 DERIVED

MeSH Terms

Conditions

Critical Illness; Malnutrition

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nutrition Disorders; Nutritional and Metabolic Diseases

Study Officials

• Daren K Heyland, MD

  Clinical Evaluation Research Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: May 17, 2017
• First Posted: May 19, 2017
• Study Start: November 21, 2017
• Primary Completion: December 3, 2021
• Study Completion: December 3, 2021
• Last Updated: March 28, 2022

Record last verified: 2022-03

Locations

AR (2); CA (10); BR (3); AU (1); ME (4); HK (1); GR (2); IR (1); PA (3); MY (1); SA (1); IN (1); US (21); PR (1); JP (2); GB (32)