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

Sponsor

Spanish Society of Critical Care Medicine and Coronary Units (Other)

Overall Status

Recruiting

CT.gov ID

NCT05918757

Collaborator

(none)

200

Enrollment

Locations

Arms

Anticipated Duration (Months)

11.1

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Intensive Care Unit Acquired Weakness	Other: Protein dose 1.5 g/kg/day Other: Protein dose 1.0 g/kg/day	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

None (Open Label)

Primary Purpose:

Other

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.

Actual Study Start Date :

Jan 1, 2022

Anticipated Primary Completion Date :

Jun 30, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change of intensive care unit acquired weakness (ICUAW). [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.]
Determined by Medical Research Council sum score (MRC-SS). Diagnosis of ICUAW if MRC-SS < 48 (maximun score 60).

Secondary Outcome Measures

Muscle Strength. [Up to 6 months.]
Dynamometry.
Active mobility. [Up to 6 months.]
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.
Nosocomial infections. [Throughout hospital stay, an expected average of 6 weeks.]
Centers for disease control and prevention (CDC).
Mechanical ventilation. [Up to 1 month.]
Number of days receiving mechanical ventilation.
Gastrointestinal complications. [Throughout hospital stay, an expected average of 6 weeks.]
Gastric residual volume, diarrhea, vomiting or regurgitation, abdominal distension, constipation.
Metabolic complications. [Throughout hospital stay, an expected average of 6 weeks.]
Glycemia, fluid intake, electrolytes/trace element determination, hypertriglyceridemia, liver disfunction, cholestasis, necrosis or mixed dysfunction, overfeeding.
Mortality rate. [Up to 6 months.]
Length of ICU and hospital stay. [Throughout hospital stay, an expected average of 6 weeks.]
Number of days of hospitalization.
Quality of life index. [Up to 6 months.]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Universitario Germans Trias i Pujol	Badalona	Barcelona	Spain	08916
2	Hospital Universitario de Bellvitge	L'Hospitalet De Llobregat	Barcelona	Spain	08907
3	Hospital General Universitario de Castellón	Castelló de la Plana	Castelló	Spain	12004
4	Hospital Universitario de Badajoz	Badajoz	Extremadura	Spain	06080
5	Hospital de Barbastro	Barbastro	Huesca	Spain	22300
6	Hospital Universitario de Fuenlabrada	Fuenlabrada	Madrid	Spain	28942
7	Hospital Universitario Infanta Cristina	Parla	MAdrid	Spain	28981
8	Hospital de Manacor	Manacor	Mallorca	Spain	07500
9	Hospital General Universitario Santa Lucía	Cartagena	Murcia	Spain	30202
10	Hospital Clínico Universitario Virgen de la Arrixaca	El Palmar	Murcia	Spain	30120
11	Hospital General Universitario Los Arcos del Mar Menor	Pozo Aledo	Murcia	Spain	30739
12	Hospital Universitario Doctor Josep Trueta	Girona		Spain	17007
13	Hospital Universitario Clínico San Cecilio	Granada		Spain	18016
14	Hospital Universitario San Jorge	Huesca		Spain	22004
15	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
16	Hospital Universitario La Paz	Madrid		Spain	28046
17	Hospital General Universitario Morales Meseguer	Murcia		Spain	30008
18	Hospital Universitario Regional de Málaga	Málaga		Spain	29010

Sponsors and Collaborators

Spanish Society of Critical Care Medicine and Coronary Units

Investigators

Principal Investigator: María Carmen Sánchez Álvarez, PhD, Sociedad Española de Medicina Intensiva Crítica y Unidades Coronarias (SEMICyUC)
Principal Investigator: Juan Francisco Fernández Ortega, PhD, Hospital Regional de Malaga