The Effect of Higher Protein Dosing in Critically Ill Patients

Critical Illness Clinical Trial

— EFFORT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03160547
• Other study ID #: The EFFORT Trial
• Status: Completed
• Phase: N/A
• Start date: November 21, 2017
• Est. completion date: December 3, 2021

Study information

• Verified date: March 2022
• Source: Clinical Evaluation Research Unit at Kingston General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1329
• Est. completion date: December 3, 2021
• Est. primary completion date: December 3, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Critical Illness
• Malnutrition

Intervention

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.
• 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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Clinical Evaluation Research Unit at Kingston General Hospital

Countries where clinical trial is conducted

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

References & Publications (6)

De Jonghe B, Sharshar T, Lefaucheur JP, Authier FJ, Durand-Zaleski I, Boussarsar M, Cerf C, Renaud E, Mesrati F, Carlet J, Raphaël JC, Outin H, Bastuji-Garin S; Groupe de Réflexion et d'Etude des Neuromyopathies en Réanimation. Paresis acquired in the intensive care unit: a prospective multicenter study. JAMA. 2002 Dec 11;288(22):2859-67. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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, Niemelä 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, Džavík 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Nutritional Adequacy	To be evaluated up to 60 days post randomization	60 day
Other	Hospital mortality	To be evaluated up to 60 days post randomization	60 day
Other	Readmission to ICU and Hospital	To be evaluated up to 60 days post randomization	60 day
Other	Duration of Mechanical Ventilation	To be evaluated up to 60 days post randomization	60 day
Other	ICU length of stay	To be evaluated up to 60 days post randomization	60 day
Other	Hospital length of stay	To be evaluated up to 60 days post randomization	60 day
Primary	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	60-day mortality	Mortality 60 days post randomization	60 day