The Effect of Higher Protein Dosing in Critically Ill Patients

NCT ID: NCT03160547

Last Updated: 2022-03-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

1329 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-21

Study Completion Date

2021-12-03

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Critical Illness Malnutrition

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Usual Protein/Amino Acid Group

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

Group Type ACTIVE_COMPARATOR

Usual Protein/Amino Acid Group

Intervention Type 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

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

Group Type ACTIVE_COMPARATOR

Higher Protein/Amino Acid Group

Intervention Type 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.

Interventions

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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.

Intervention Type 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.

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Clinical Evaluation Research Unit at Kingston General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Daren K. Heyland

Director

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Daren K Heyland, MD

Role: PRINCIPAL_INVESTIGATOR

Clinical Evaluation Research Unit

Locations

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Banner University Medical Center

Phoenix, Arizona, United States

Site Status

Phoenix VA Health Care System

Phoenix, Arizona, United States

Site Status

MemorialCare Long Beach Medical Center

Long Beach, California, United States

Site Status

NorthShore University HealthSystem

Evanston, Illinois, United States

Site Status

SwedishAmercian.Hospital

Rockford, Illinois, United States

Site Status

IU Health Methodist Hospital

Indianapolis, Indiana, United States

Site Status

Lahey Hospital and Medical Center

Burlington, Massachusetts, United States

Site Status

Spectrum Health

Grand Rapids, Michigan, United States

Site Status

Virtua

Marlton, New Jersey, United States

Site Status

Virtua

Mount Holly, New Jersey, United States

Site Status

Virtua

Voorhees Township, New Jersey, United States

Site Status

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Site Status

Fairfield Medical Center

Lancaster, Ohio, United States

Site Status

OU Medical Center

Oklahoma City, Oklahoma, United States

Site Status

Hospital of the University of Pennsylvania - MICU

Philadelphia, Pennsylvania, United States

Site Status

University of Tennessee Medical Center Knoxville

Knoxville, Tennessee, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

University of Virginia Health System

Charlottesville, Virginia, United States

Site Status

Harborview Medical Center

Seattle, Washington, United States

Site Status

Legacy Salmon Creek Medical Center

Vancouver, Washington, United States

Site Status

Froedtert Memorial Lutheran Hospital

Milwaukee, Wisconsin, United States

Site Status

Hospital Britanico de Buenos Aires

Buenos Aires, , Argentina

Site Status

Sanatorio Allende

Córdoba, , Argentina

Site Status

Gold Coast Hospital and Health Service

Gold Coast, , Australia

Site Status

Casa de Saude Sao Jose

Rio de Janeiro, , Brazil

Site Status

Hospital e Clinica Sao Goncalo

Rio de Janeiro, , Brazil

Site Status

Hospital Icarai

Rio de Janeiro, , Brazil

Site Status

Royal Alexandra Hospital

Edmonton, Alberta, Canada

Site Status

University of Alberta

Edmonton, Alberta, Canada

Site Status

Abbotsford Regional Hospital

Abbotsford, British Columbia, Canada

Site Status

Burnaby Hospital

Burnaby, British Columbia, Canada

Site Status

Royal Columbian Hospital

New Westminster, British Columbia, Canada

Site Status

Surrey Memorial Hospital

Surrey, British Columbia, Canada

Site Status

London Health Sciences Center Hospital

London, Ontario, Canada

Site Status

Grey Bruce Health Services

Owen Sound, Ontario, Canada

Site Status

Mount Sinai Hospital

Toronto, Ontario, Canada

Site Status

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

Montreal, Quebec, Canada

Site Status

Agioi Anargiroi Hospital

Athens, , Greece

Site Status

Evangelismos General Hospital

Athens, , Greece

Site Status

Queen Mary Hospital

Hong Kong, , Hong Kong

Site Status

Apollo Hospitals Enterprises Limited

Mumbai, , India

Site Status

Emam Reza Hospital, Mashhad University of Medical Science

Mashhad, , Iran

Site Status

Kobe City Medical Center General Hospital

Kobe, Hyōgo, Japan

Site Status

National Disaster Medical Center

Tokyo, Midori-cho, Tachikawa-shi, Japan

Site Status

University of Malaya Medical Centre

Kuala Lumpur, , Malaysia

Site Status

Hospital San Javier

Guadalajara, Jalisco, Mexico

Site Status

Hospital Civil Fray Antonio Alcalde

Guadalajara, Jalisco, Mexico

Site Status

Hospital General Dr. Manuel Gea Gonzalez

Mexico City, Mexico City, Mexico

Site Status

Hospital Angeles Lomas

México, State of Mexico, Mexico

Site Status

Hospital Regional Rafael Hernandez L. David Chiriqui Css

David, Chiriquí Province, Panama

Site Status

Hospital Irma De Lourdes Tzanetatos

Panama City, , Panama

Site Status

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

Panama City, , Panama

Site Status

Hospital Himas San Pablo Caguas

Caguas, , Puerto Rico

Site Status

King Faisal Specialist Hospital and Research Center

Riyadh, , Saudi Arabia

Site Status

University Southampton NHS Trust

Southampton, Hampshire, United Kingdom

Site Status

Royal Blackburn Hospital

Blackburn, , United Kingdom

Site Status

North Bristol NHS Trust

Bristol, , United Kingdom

Site Status

Addenbrooke's Hospital

Cambridge, , United Kingdom

Site Status

St Richards Hospital

Chichester, , United Kingdom

Site Status

Northumbria Emergency Care Hospital

Cramlington, , United Kingdom

Site Status

Royal Infirmary of Edinburgh

Edinburgh, , United Kingdom

Site Status

Queen Elizabeth Hospital

Gateshead, , United Kingdom

Site Status

Medway Maritime Hospital

Gillingham, , United Kingdom

Site Status

Northwick Park hospital

Harrow, , United Kingdom

Site Status

East Suffolk & North Essex Foundation Trust

Ipswich, , United Kingdom

Site Status

The Queen Elizabeth Hospital Kings Lynn NHS Trust

Kings Lynn, , United Kingdom

Site Status

Royal Glamorgan Hospital

Llantrisant, , United Kingdom

Site Status

Colchester Hospital

London, , United Kingdom

Site Status

Guy's and St Thomas' NHS Foundation Trust

London, , United Kingdom

Site Status

Kings College Hospital Denmark Hill

London, , United Kingdom

Site Status

Queen Elizabeth Hospital

London, , United Kingdom

Site Status

Royal Free London NHS Foundation Trust

London, , United Kingdom

Site Status

University Hospital Lewisham

London, , United Kingdom

Site Status

Queen Elizabeth the Queen Mother Hospital

Margate, , United Kingdom

Site Status

Freeman Hospital

Newcastle, , United Kingdom

Site Status

Aneurin bevan University Health Board

Newport, , United Kingdom

Site Status

Nottingham University Hospitals NHS Trust

Nottingham, , United Kingdom

Site Status

The Tunbridge Wells Hospital

Pembury, , United Kingdom

Site Status

Queen Alexandra

Portsmouth, , United Kingdom

Site Status

Royal Preston Hospital

Preston, , United Kingdom

Site Status

Lister Hospital East and North Hertfordshire Trust

Stevenage, , United Kingdom

Site Status

Royal Stoke Hospital

Stoke-on-Trent, , United Kingdom

Site Status

Sunderland Royal Hospital

Sunderland, , United Kingdom

Site Status

Torbay Hospital

Torquay, , United Kingdom

Site Status

Worthing Hospital

Worthing, , United Kingdom

Site Status

Yeovil District Hospital NHS Foundation Trust

Yeovil, , United Kingdom

Site Status

Countries

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United States Argentina Australia Brazil Canada Greece Hong Kong India Iran Japan Malaysia Mexico Panama Puerto Rico Saudi Arabia United Kingdom

References

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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.

Reference Type BACKGROUND
PMID: 22811443 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21705881 (View on PubMed)

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.

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PMID: 25853743 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24247473 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12472328 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24825371 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38354904 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38229072 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37930244 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37853490 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36708732 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32669140 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Informed Consent Form

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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The EFFORT Trial

Identifier Type: -

Identifier Source: org_study_id

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