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

Intensive Care Unit Acquired Weakness Clinical Trial

— FISIO  

Official title:

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05918757
• Other study ID #: ASF1
• Secondary ID: 2021-002329-56
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2022
• Est. completion date: June 30, 2024

Study information

• Verified date: December 2023
• Source: Spanish Society of Critical Care Medicine and Coronary Units
• Contact: María Carmen Sánchez Álvarez, PhD
• Phone: +34915021213
• Email: carmelasanchez757[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: June 30, 2024
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Critical Illness
• Intensive Care Unit Acquired Weakness

Intervention

Other:
• Protein dose 1.5 g/kg/day
Administration of 1.5 g of protein/kg/day via enteral/parenteral nutrition
• Protein dose 1.0 g/kg/day
Administration of 1.0 g of protein/kg/day via enteral/parenteral nutrition

Locations

Country	Name	City	State
Spain	Hospital Universitario de Badajoz	Badajoz	Extremadura
Spain	Hospital Universitario Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital de Barbastro	Barbastro	Huesca
Spain	Hospital General Universitario Santa Lucía	Cartagena	Murcia
Spain	Hospital General Universitario de Castellón	Castelló de la Plana	Castelló
Spain	Hospital Clínico Universitario Virgen de la Arrixaca	El Palmar	Murcia
Spain	Hospital Universitario de Fuenlabrada	Fuenlabrada	Madrid
Spain	Hospital Universitario Doctor Josep Trueta	Girona
Spain	Hospital Universitario Clínico San Cecilio	Granada
Spain	Hospital Universitario San Jorge	Huesca
Spain	Hospital Universitario de Bellvitge	L'Hospitalet De Llobregat	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Regional de Málaga	Málaga
Spain	Hospital de Manacor	Manacor	Mallorca
Spain	Hospital General Universitario Morales Meseguer	Murcia
Spain	Hospital Universitario Infanta Cristina	Parla	MAdrid
Spain	Hospital General Universitario Los Arcos del Mar Menor	Pozo Aledo	Murcia

Sponsors (1)

Lead Sponsor	Collaborator
Spanish Society of Critical Care Medicine and Coronary Units

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Muscle Strength.	Dynamometry.	Up to 6 months.
Secondary	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.
Secondary	Nosocomial infections.	Centers for disease control and prevention (CDC).	Throughout hospital stay, an expected average of 6 weeks.
Secondary	Mechanical ventilation.	Number of days receiving mechanical ventilation.	Up to 1 month.
Secondary	Gastrointestinal complications.	Gastric residual volume, diarrhea, vomiting or regurgitation, abdominal distension, constipation.	Throughout hospital stay, an expected average of 6 weeks.
Secondary	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.
Secondary	Mortality rate.		Up to 6 months.
Secondary	Length of ICU and hospital stay.	Number of days of hospitalization.	Throughout hospital stay, an expected average of 6 weeks.
Secondary	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.