Clinical trial NCT03160547: The Effect of Higher Protein Dosing in Critically Ill Patients
Official title: The Effect of Higher Protein Dosing in Critically Ill Patients: A Multicenter Registry-based Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Critical Illness
Malnutrition
Lead sponsor: Clinical Evaluation Research Unit at Kingston General Hospital
Sponsor class: OTHER
First posted: 2017-05-19
Enrollment: 1329
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time to discharge alive from hospital
timeFrame: 60 day
Secondary outcomes:
measure: 60-day mortality
timeFrame: 60 day
Other outcomes:
measure: Nutritional Adequacy
timeFrame: 60 day
measure: Hospital mortality
timeFrame: 60 day
measure: Readmission to ICU and Hospital
timeFrame: 60 day
measure: Duration of Mechanical Ventilation
timeFrame: 60 day
measure: ICU length of stay
timeFrame: 60 day
measure: Hospital length of stay
timeFrame: 60 day
Locations:
city: Phoenix
country: United States
facility: Banner University Medical Center
state: Arizona
city: Phoenix
country: United States
facility: Phoenix VA Health Care System
state: Arizona
city: Long Beach
country: United States
facility: MemorialCare Long Beach Medical Center
state: California
city: Evanston
country: United States
facility: NorthShore University HealthSystem
state: Illinois
city: Rockford
country: United States
facility: SwedishAmercian.Hospital
state: Illinois
city: Indianapolis
country: United States
facility: IU Health Methodist Hospital
state: Indiana
city: Burlington
country: United States
facility: Lahey Hospital and Medical Center
state: Massachusetts
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
city: Marlton
country: United States
facility: Virtua
state: New Jersey
city: Mount Holly
country: United States
facility: Virtua
state: New Jersey
city: Voorhees
country: United States
facility: Virtua
state: New Jersey
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Lancaster
country: United States
facility: Fairfield Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: OU Medical Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania - MICU
state: Pennsylvania
city: Knoxville
country: United States
facility: University of Tennessee Medical Center Knoxville
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Vancouver
country: United States
facility: Legacy Salmon Creek Medical Center
state: Washington
city: Milwaukee
country: United States
facility: Froedtert Memorial Lutheran Hospital
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Hospital Britanico de Buenos Aires
city: Cordoba
country: Argentina
facility: Sanatorio Allende
city: Gold Coast
country: Australia
facility: Gold Coast Hospital and Health Service
city: Rio de Janeiro
country: Brazil
facility: Casa de Saude Sao Jose
city: Rio de Janeiro
country: Brazil
facility: Hospital e Clinica Sao Goncalo
city: Rio de Janeiro
country: Brazil
facility: Hospital Icarai
city: Edmonton
country: Canada
facility: Royal Alexandra Hospital
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Abbotsford
country: Canada
facility: Abbotsford Regional Hospital
state: British Columbia
city: Burnaby
country: Canada
facility: Burnaby Hospital
state: British Columbia
city: New Westminster
country: Canada
facility: Royal Columbian Hospital
state: British Columbia
city: Surrey
country: Canada
facility: Surrey Memorial Hospital
state: British Columbia
city: London
country: Canada
facility: London Health Sciences Center Hospital
state: Ontario
city: Owen Sound
country: Canada
facility: Grey Bruce Health Services
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Montreal
country: Canada
facility: CIUSSS de l'Est-de-l'ile-de-Montreal- Installation Hospital Maisonneuve-Rosemont
state: Quebec
city: Athens
country: Greece
facility: Agioi Anargiroi Hospital
city: Athens
country: Greece
facility: Evangelismos General Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Mumbai
country: India
facility: Apollo Hospitals Enterprises Limited
city: Mashhad
country: Iran, Islamic Republic of
facility: Emam Reza Hospital, Mashhad University of Medical Science
city: Kobe
country: Japan
facility: Kobe City Medical Center General Hospital
state: Hyogo
city: Tokyo
country: Japan
facility: National Disaster Medical Center
state: Midori-cho, Tachikawa-shi
city: Kuala Lumpur
country: Malaysia
facility: University of Malaya Medical Centre
city: Mexico City
country: Mexico
facility: Hospital General Dr. Manuel Gea Gonzalez
state: Cdmx
city: Mexico City
country: Mexico
facility: Hospital Angeles Lomas
state: Estado De Mexico
city: Guadalajara
country: Mexico
facility: Hospital San Javier
state: Jalisco
city: Guadalajara
country: Mexico
facility: Hospital Civil Fray Antonio Alcalde
state: Jalisco
city: David
country: Panama
facility: Hospital Regional Rafael Hernandez L. David Chiriqui Css
state: Chiriqui
city: Panamá
country: Panama
facility: Hospital Irma De Lourdes Tzanetatos
city: Panamá
country: Panama
facility: Complejo Hospitalario Dr. Arnulfo Arias Madrid de la Caja de Seguro Social
city: Caguas
country: Puerto Rico
facility: Hospital Himas San Pablo Caguas
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specialist Hospital and Research Center
city: Southampton
country: United Kingdom
facility: University Southampton NHS Trust
state: Hampshire
city: Blackburn
country: United Kingdom
facility: Royal Blackburn Hospital
city: Bristol
country: United Kingdom
facility: North Bristol NHS Trust
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Chichester
country: United Kingdom
facility: St Richards Hospital
city: Cramlington
country: United Kingdom
facility: Northumbria Emergency Care Hospital
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
city: Gateshead
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Gillingham
country: United Kingdom
facility: Medway Maritime Hospital
city: Harrow
country: United Kingdom
facility: Northwick Park hospital
city: Ipswich
country: United Kingdom
facility: East Suffolk & North Essex Foundation Trust
city: King's Lynn
country: United Kingdom
facility: The Queen Elizabeth Hospital Kings Lynn NHS Trust
city: Llantrisant
country: United Kingdom
facility: Royal Glamorgan Hospital
city: London
country: United Kingdom
facility: Colchester Hospital
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: Kings College Hospital Denmark Hill
city: London
country: United Kingdom
facility: Queen Elizabeth Hospital
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: London
country: United Kingdom
facility: University Hospital Lewisham
city: Margate
country: United Kingdom
facility: Queen Elizabeth the Queen Mother Hospital
city: Newcastle
country: United Kingdom
facility: Freeman Hospital
city: Newport
country: United Kingdom
facility: Aneurin bevan University Health Board
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Pembury
country: United Kingdom
facility: The Tunbridge Wells Hospital
city: Portsmouth
country: United Kingdom
facility: Queen Alexandra
city: Preston
country: United Kingdom
facility: Royal Preston Hospital
city: Stevenage
country: United Kingdom
facility: Lister Hospital East and North Hertfordshire Trust
city: Stoke-on-Trent
country: United Kingdom
facility: Royal Stoke Hospital
city: Sunderland
country: United Kingdom
facility: Sunderland Royal Hospital
city: Torquay
country: United Kingdom
facility: Torbay Hospital
city: Worthing
country: United Kingdom
facility: Worthing Hospital
city: Yeovil
country: United Kingdom
facility: Yeovil District Hospital NHS Foundation Trust
Study officials:
affiliation: Clinical Evaluation Research Unit
name: Daren K Heyland, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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, 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.
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.
citation: 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.
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.
citation: 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.