Efficacy and Safety of Administration of High Levels of Protein to Critically Ill Patients. (FISIO)

Exploratory Study to Evaluate the Efficacy and Safety of Nutritional Administration of 1.5 g of Protein/kg/Day Versus 1.0 g of Protein/kg/Day in the Catabolic Phase of Critically Ill Patients Receiving Mechanical Ventilation.

Critically ill patients are known to develop serious nutritional deterioration during the course of their disease. They develop, from the beginning, a multifactorial protein malnutrition that relates to a poor clinical course and the development of weakness. Due to the increased protein catabolism in this type of patient, there is a rapid degradation of muscle mass and loss of functional proteins, and therefore nutritional support is mandatory. Indeed, achieving a high protein intake may promote a better evolution of the critically ill patient, i.e., maintenance of muscle protein, less deterioration of muscle strength, lower Intensive care unit-acquired weakness (ICUAW), lower mortality, decrease in the number of infections, decrease in days on mechanical ventilation, and days of hospital stay and in ICU.

The goal of this clinical trial is to compare the appearance and degree of ICUAW in critically ill patients receiving invasive mechanical ventilation treated with two different doses of protein (1.5 g/kg/day vs.1.0 g/kg/day).

Study Overview

• Status: Recruiting
• Conditions: Intensive Care Unit Acquired Weakness
• Intervention / Treatment: Other: Protein dose 1.5 g/kg/day; Other: Protein dose 1.0 g/kg/day

Detailed Description

It is known that protein metabolism is altered in critically ill patients due to metabolic alterations derived from stress. This critical situation is manifested by a severe catabolic alteration, especially in the first week, which is fundamentally characterized by severe glucose intolerance and the use of the protein itself as a metabolic substrate.

Despite protein synthesis is increased, this is insufficient to compensate for the high protein degradation rate, which leads, among others, to muscle deterioration resulting in increased morbidity and mortality. This muscle destruction has been implicated in the early appearance of Intensive care unit-acquired weakness (ICUAW). Although the pathophysiology of ICUAW is multifactorial, protein intake may play an key role in its treatment. However, protein intake cannot reduce muscle destruction, but it can stimulate protein synthesis.

Current evidence supports that the administration of early artificial nutritional support with a high protein intake can improve the clinical course of critically ill patients. However, there is still no consensus on the exact amount of protein needed to be administered to these patients in order to reduce adverse outcomes and prevent ICUAW.

Thus the aim of this study is to evaluate the effect of a nutritional supplementation containing 1.5 g of protein/kg/day vs 1.0 g of protein /kg/day in critically ill patients receiving mechanical ventilation on the development and degree of ICUAW.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: María Carmen Sánchez Álvarez, PhD; Phone Number: +34915021213; Email: carmelasanchez757@gmail.com
• Study Contact Backup: Name: Juan Francisco Fernández Ortega, PhD; Phone Number: +34951290000; Email: jfezortega@gmail.com

Study Locations

• Spain
  • Girona, Spain, 17007
    • Recruiting
    • Hospital Universitario Doctor Josep Trueta
    • Contact: Carolina Lorencio Cárdenas, PhD; Phone Number: +34972940200; Email: carol_lorencio@hotmail.com
    • Principal Investigator: Carolina Lorencio Cárdenas, PhD
    • Sub-Investigator: Meritxell Lladó Vilar, PhD
    • Sub-Investigator: Neus Senyer Esquerra, MD
  • Granada, Spain, 18016
    • Recruiting
    • Hospital Universitario Clínico San Cecilio
    • Contact: Manuel Colmenero Ruiz, PhD; Phone Number: +34958023000; Email: manuel.colmenero.sspa@juntadeandalucia.es
    • Principal Investigator: Manuel Colmenero Ruiz, PhD
    • Sub-Investigator: Josefina Moreno López, PhD
    • Sub-Investigator: Jesús Giménez Gutiérrez, PhD
  • Huesca, Spain, 22004
    • Recruiting
    • Hospital Universitario San Jorge
    • Contact: Carlos Serón Arbeloa, MD; Phone Number: +34974247000; Email: cseron@unizar.es
    • Principal Investigator: Carlos Serón Arbeloa, MD
    • Sub-Investigator: Alberto Lafita Pérez, PhD
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
    • Contact: José Luis Flordelis Lasierra, MD; Phone Number: +34913908000; Email: makalyconru@hotmail.com
    • Principal Investigator: José Luis Flordelis Lasierra, MD
    • Sub-Investigator: Mónica Fuentes Ponte, MD
    • Sub-Investigator: Helena Dominguez Aguado, MD
    • Sub-Investigator: Laura Campos Bermejo, RN
    • Sub-Investigator: Maria Luz Montero González, RN
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
    • Contact: Lucía Cachafeiro Fuciños, PhD; Phone Number: +34917277000; Email: luciacachafeiro@yahoo.es
    • Principal Investigator: Lucía Cachafeiro Fuciños, PhD
    • Sub-Investigator: Alexander Agrifolio Rotaeche, PhD
  • Murcia, Spain, 30008
    • Recruiting
    • Hospital General Universitario Morales Meseguer
    • Contact: Maravillas de las Nieves Alcázar Espín, PhD; Phone Number: +34968360900; Email: mavialcazar@hotmail.com
    • Principal Investigator: Maravillas de las Nieves Alcázar Espín, PhD
    • Sub-Investigator: Pilar Tornero Yepez, MD
  • Málaga, Spain, 29010
    • Recruiting
    • Hospital Universitario Regional de Málaga
    • Contact: Juan Francisco Martínez Carmona, PhD; Phone Number: +34951290000; Email: jf.mtnez88@gmail.com
    • Principal Investigator: Juan Francisco Martínez Carmona, PhD
    • Principal Investigator: Juan Francisco Fernández Ortega, MD
    • Sub-Investigator: Giulia Guidetti, MD
    • Sub-Investigator: Rosa María Barraso González, MD
    • Sub-Investigator: Ana Isabel Robles Rodríguez, MD
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Recruiting
      • Hospital Universitario Germans Trias i Pujol
      • Contact: Luisa Bordejé Laguna, MD; Phone Number: +34934651200; Email: luisabordeje@gmail.com
      • Principal Investigator: Luisa Bordejé Laguna, MD
      • Sub-Investigator: Esther Mor Marco, MD
    • L'Hospitalet De Llobregat, Barcelona, Spain, 08907
      • Recruiting
      • Hospital Universitario de Bellvitge
      • Contact: Victor Manuel Gumicio Sanguino, MD; Phone Number: +34932607500; Email: vgumucio@bellvitgehospital.cat
      • Principal Investigator: Victor Manuel Gumicio Sanguino, MD
  • Castelló
    • Castelló de la Plana, Castelló, Spain, 12004
      • Recruiting
      • Hospital General Universitario de Castellón
      • Contact: María Lidón Mateu Campos, MD; Phone Number: +34964725000; Email: lidonmateu@gmail.com
      • Principal Investigator: María Lidón Mateu Campos, MD
      • Sub-Investigator: Fernando Sánchez Morán, MD
  • Extremadura
    • Badajoz, Extremadura, Spain, 06080
      • Recruiting
      • Hospital Universitario de Badajoz
      • Contact: Mariola Cerezo Arias, PhD; Phone Number: +34924218100; Email: mariolacerezo@yahoo.es
      • Principal Investigator: Mariola Cerezo Arias, PhD
      • Sub-Investigator: María Dolores Pérez Frutos, PhD
      • Sub-Investigator: Isabel María López Esteban, MD
  • Huesca
    • Barbastro, Huesca, Spain, 22300
      • Recruiting
      • Hospital de Barbastro
      • Contact: Carlos González Iglesias, MD; Phone Number: +34974249000; Email: cgisalamanca@hotmail.com
      • Principal Investigator: Carlos González Iglesias, MD
      • Sub-Investigator: Mónica Zamora Elson, PhD
  • MAdrid
    • Parla, MAdrid, Spain, 28981
      • Recruiting
      • Hospital Universitario Infanta Cristina
      • Contact: Belén Vila García, PhD; Phone Number: +34911913000; Email: belenvilag@yahoo.es
      • Principal Investigator: Belén Vila García, PhD
      • Sub-Investigator: Marcela Homez Guzmán, MD
  • Madrid
    • Fuenlabrada, Madrid, Spain, 28942
      • Recruiting
      • Hospital Universitario de Fuenlabrada
      • Contact: Clara Vaquerizo Alonso, MD; Phone Number: +34916006000; Email: clara.vaquerizo@salud.madrid.org
      • Principal Investigator: Clara Vaquerizo Alonso, MD
      • Sub-Investigator: Gema Díaz Cuero, MD
      • Sub-Investigator: Gema Candelaria Arellano del Verbo, MD
      • Sub-Investigator: Paula Taboada Dominguez, MD
  • Mallorca
    • Manacor, Mallorca, Spain, 07500
      • Recruiting
      • Hospital de Manacor
      • Contact: Rosa Gastaldo Simeón, MD; Phone Number: +34971847000; Email: rousgastaldi@hotmail.com
      • Principal Investigator: Rosa Gastaldo Simeón, MD
      • Sub-Investigator: Violeta Cano Collado, MD
  • Murcia
    • Cartagena, Murcia, Spain, 30202
      • Recruiting
      • Hospital General Universitario Santa Lucía
      • Contact: beatriz Perez Perez, PhD; Phone Number: +34968128600; Email: beatriz_perez5@hotmail.com
      • Principal Investigator: Beatriz Pérez Pérez, PhD
      • Sub-Investigator: Angel Fernández Martínez, MD
    • El Palmar, Murcia, Spain, 30120
      • Recruiting
      • Hospital Clinico Universitario Virgen de la Arrixaca
      • Contact: Rubén Jara Rubio, MD; Phone Number: +34968369500; Email: rjarafibio@yahoo.es
      • Principal Investigator: Rubén Jara Rubio, MD
      • Sub-Investigator: María Martínez Martínez, MD
      • Sub-Investigator: María Ángeles Núñez Sánchez, PhD
      • Sub-Investigator: Domingo Martínez Baños, MD
    • Pozo Aledo, Murcia, Spain, 30739
      • Recruiting
      • Hospital General Universitario Los Arcos del Mar Menor
      • Contact: Nuria Molina Sánchez, PhD; Phone Number: +34968565000; Email: nurihelen@gmail.com
      • Principal Investigator: Nuria Molina Sánchez, PhD
      • Sub-Investigator: Francisco García Córdoba, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Critically ill patient
• ICU admission during the previous 48h
• Patients on expected invasive mechanical ventilation for three days
• Patients with a minimum expected duration of clinical nutrition of at least seven days
• Written informed consent signed by the patient or the patient's legally authorized representative.
• Available central venous access for continuous infusion of the study drugs.

Exclusion Criteria:

• Denied informed consent
• Acute renal failure (renal injury stage 3)
• Liver failure (cirrhosis or Child-Pugh Scale > 5)
• Severe liver failure with International Normalized Ratio (INR) > 1.7 (prothrombin time > 50%) and encephalopathy
• Patients with COVID-19-derived pneumonia
• Body Mass Index (BMI) > 40 or < 18.5 (morbid obesity or previous caloric malnutrition)
• Pregnant patients
• Central Nervous System pathologies (Glasgow < 6)
• Peripheral Nervous System pathologies interfering with study evaluations
• Patients with cognitive dysfunction/dementia or unable to follow instructions regarding MRC tests
• Severe muscular pathology
• Already participating in another clinical trial
• Impossibility to contact after ICU discharge to carry out the follow-up visit on day 90
• Known hypersensitivity to milk protein or any of the components of the nutritional supplement
• Inborn errors in the amino acid metabolism
• Previous inclusion in the present study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Protein dose 1.5 g/kg/day; Administration of 1.5 g of protein/kg/day in critically ill patients receiving invasive mechanical ventilation	Other: Protein dose 1.5 g/kg/day; Administration of 1.5 g of protein/kg/day via enteral/parenteral nutrition
Active Comparator: Protein dose 1.0 g/kg/day; Administration of 1.0 g of protein/kg/day in critically ill patients receiving invasive mechanical ventilation	Other: Protein dose 1.0 g/kg/day; Administration of 1.0 g of protein/kg/day via enteral/parenteral nutrition

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of intensive care unit acquired weakness (ICUAW).	Determined by Medical Research Council sum score (MRC-SS). Diagnosis of ICUAW if MRC-SS < 48 (maximun score 60).	Baseline, weekly in ICU up to 28 days after mechanical ventilation termination, throughout hospital stay, an expected average of 6 weeks, and 90 days after hospital discharge.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle Strength.	Dynamometry.	Up to 6 months.
Active mobility.	Determined by Intensive Care Unit Mobility Scale (ICUMS). Scored from 0 to 10 being 0 no activity, lying in bed, and 10 walking independently without a gait aid.	Up to 6 months.
Nosocomial infections.	Centers for disease control and prevention (CDC).	Throughout hospital stay, an expected average of 6 weeks.
Mechanical ventilation.	Number of days receiving mechanical ventilation.	Up to 1 month.
Gastrointestinal complications.	Gastric residual volume, diarrhea, vomiting or regurgitation, abdominal distension, constipation.	Throughout hospital stay, an expected average of 6 weeks.
Metabolic complications.	Glycemia, fluid intake, electrolytes/trace element determination, hypertriglyceridemia, liver disfunction, cholestasis, necrosis or mixed dysfunction, overfeeding.	Throughout hospital stay, an expected average of 6 weeks.
Mortality rate.		Up to 6 months.
Length of ICU and hospital stay.	Number of days of hospitalization.	Throughout hospital stay, an expected average of 6 weeks.
Quality of life index.	European Quality of Life-5 Dimensions (EQ-5D). Scored from 0 to 100 being 0 the worst health imaginable and 100 the best health imaginable.	Up to 6 months.

Collaborators and Investigators

• Sponsor: Spanish Society of Critical Care Medicine and Coronary Units
• Investigators: Principal Investigator: Juan Francisco Fernández Ortega, PhD, Hospital Regional De Malaga; Principal Investigator: María Carmen Sánchez Álvarez, PhD, Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC)

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Estimated): March 31, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: May 30, 2023
• First Submitted That Met QC Criteria: June 15, 2023
• First Posted (Actual): June 26, 2023

Study Record Updates

• Last Update Posted (Actual): December 4, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Mechanical ventilation; Critically ill; Parenteral nutrition; Enteral nutrition; Protein dose
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: ASF1; 2021-002329-56 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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