Clinical trial NCT05918757: Efficacy and Safety of Administration of High Levels of Protein to Critically Ill Patients.
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.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Intensive Care Unit Acquired Weakness
Keywords: Critically ill
Mechanical ventilation
Parenteral nutrition
Enteral nutrition
Protein dose
Lead sponsor: Spanish Society of Critical Care Medicine and Coronary Units
Sponsor class: OTHER
First posted: 2023-06-26
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Within 48 hours, intensive care patients on expected invasive mechanical ventilation of at least three days are allocated into two groups receiving enteral/parenteral nutrition with 1.5 g of protein/kg/day or 1.0 g of protein/kg/day as an active comparator.
Primary purpose: OTHER

Brief 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change of intensive care unit acquired weakness (ICUAW).
timeFrame: 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 outcomes:
measure: Muscle Strength.
timeFrame: Up to 6 months.
measure: Active mobility.
timeFrame: Up to 6 months.
measure: Nosocomial infections.
timeFrame: Throughout hospital stay, an expected average of 6 weeks.
measure: Mechanical ventilation.
timeFrame: Up to 1 month.
measure: Gastrointestinal complications.
timeFrame: Throughout hospital stay, an expected average of 6 weeks.
measure: Metabolic complications.
timeFrame: Throughout hospital stay, an expected average of 6 weeks.
measure: Mortality rate.
timeFrame: Up to 6 months.
measure: Length of ICU and hospital stay.
timeFrame: Throughout hospital stay, an expected average of 6 weeks.
measure: Quality of life index.
timeFrame: Up to 6 months.
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
state: Barcelona
city: L'Hospitalet De Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge
state: Barcelona
city: Castelló de la Plana
country: Spain
facility: Hospital General Universitario de Castellón
state: Castelló
city: Badajoz
country: Spain
facility: Hospital Universitario de Badajoz
state: Extremadura
city: Barbastro
country: Spain
facility: Hospital de Barbastro
state: Huesca
city: Fuenlabrada
country: Spain
facility: Hospital Universitario de Fuenlabrada
state: Madrid
city: Parla
country: Spain
facility: Hospital Universitario Infanta Cristina
state: MAdrid
city: Manacor
country: Spain
facility: Hospital de Manacor
state: Mallorca
city: Cartagena
country: Spain
facility: Hospital General Universitario Santa Lucía
state: Murcia
city: El Palmar
country: Spain
facility: Hospital Clínico Universitario Virgen de la Arrixaca
state: Murcia
city: Pozo Aledo
country: Spain
facility: Hospital General Universitario Los Arcos del Mar Menor
state: Murcia
city: Girona
country: Spain
facility: Hospital Universitario Doctor Josep Trueta
city: Granada
country: Spain
facility: Hospital Universitario Clínico San Cecilio
city: Huesca
country: Spain
facility: Hospital Universitario San Jorge
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Murcia
country: Spain
facility: Hospital General Universitario Morales Meseguer
city: Málaga
country: Spain
facility: Hospital Universitario Regional de Málaga
Study officials:
affiliation: Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC)
name: María Carmen Sánchez Álvarez, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Regional de Malaga
name: Juan Francisco Fernández Ortega, PhD
role: PRINCIPAL_INVESTIGATOR
References: