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Indirect Calorimeter Based Study in Patients With Liver Cirrhosis (METALIC)

Primary Purpose

Liver Cirrhoses

Status
Completed
Phase
Not Applicable
Locations
India
Study Type
Interventional
Intervention
Indirect calorimetry based nutritional intervention till patient in ICU(Intensive care unit)
Standard and fixed nutritional intervention till patient in ICU
Sponsored by
Institute of Liver and Biliary Sciences, India
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Cirrhoses focused on measuring Indirect calorimeter, Resting energy expenditure, substrate utilization, nitrogen balance

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Disease groups:

• Patients with liver cirrhosis (diagnosis established based on routine clinical, biochemical and at least radiological, endoscopic or histological parameters.) admitted in Liver coma Intensive care unit and those admitted in ward.

Disease controls:

  • Patients with Acute liver failure (diagnosis established based on routine clinical, biochemical and at least radiological parameters) admitted in Liver coma Intensive care unit
  • Patients with severe acute pancreatitis (diagnosis established based on routine clinical, biochemical and at least radiological parameters) admitted in Liver coma Intensive care unit

Healthy Controls:

  • Healthy subjects- Relatives of patients with no known chronic diseases (Chronic obstructive pulmonary disease, Coronary artery disease, Type 2 diabetes, Hypertension, Hypothyroidism, Koch's disease) or not on any long term medications.
  • Patients with liver cirrhosis (diagnosis established based on routine clinical, biochemical and at least radiological, endoscopic or histological parameters.) admitted in Liver coma Intensive care unit who require mechanical ventilation

Exclusion Criteria:

  • Age<18 years
  • Active upper gastrointestinal bleeding
  • If there are conditions which precluded IC, such as an FiO2 >60 %, failure to cooperate, agitation, seizure activity, spasticity, or positive end-expiratory pressure (PEEP) >10 mmHg.
  • Pregnant women
  • Refused to consent/ inability to obtain informed consent.
  • Known long standing diabetic
  • If there is any evidence of medical/surgical instability
  • Hepatocellular carcinoma Extrahepatic malignancies
  • With persistent gastrointestinal dysfunction and ileus
  • Patients who would be readmitted to the ICU
  • Known long standing diabetic
  • Terminally ill patients on high inotropic support
  • Acute liver failure
  • If there is any evidence of medical/surgical instability
  • If patients are taking any portion of nutrition by mouth.
  • Pregnant women
  • Refused to consent/ inability to obtain informed consent.
  • Patient on CRRT- continuous renal replacement therapy
  • Severe co morbidities such as Chronic kidney disease requiring maintenance dialysis, COPD and Cardiac pathologies (Acute myocardial infarction, heart failure, ).
  • Hepatocellular carcinoma Extrahepatic malignancies
  • Moribund patient with likely survival <24 hours
  • Patients enrolled in other drug trials.

Sites / Locations

  • ILBS

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Control arm

Intervention arm

Arm Description

This is the group of critically ill cirrhotic patients on mechanical ventilator support who would receive the nutritional therapy as per the standard enteral nutritional practice in a critical care setting in cirrhotics till the period admitted in ICU(Intensive care unit) 35-40 Kcal/Kg IBW/day; 1.5g protein per kg per day.

This is the group of critically ill cirrhotic patients on mechanical ventilator support who would receive the nutritional therapy based on indirect calorimetry measurements till the period admitted in ICU(Intensive care unit); 1.5g protein per kg per day.

Outcomes

Primary Outcome Measures

Part 1: An Observational study
Study groups : Healthy controls Disease Groups Patients with liver cirrhosis (compensated and decompensated) Critically ill cirrhotics on mechanical ventilator support patients with chronic kidney disease (CKD) (stable,non dialyzed, non oliguric outpatients) Critically ill patients with Acute liver failure (ALF) on mechanical ventilator support Critically ill patients with Acute on chronic liver failure(ACLF) on mechanical ventilator support Severe acute pancreatitis on mechanical ventilator support Comparison of the prevalence of hyper and hypo metabolism in patients with chronic liver disease(CLD) and healthy controls and other disease groups.
Part 2: A Randomized controlled trial
Study group:Critically ill Cirrhotic: Diagnosed cases of liver cirrhosis with 2 or more organ failures (liver + renal/circulatory or respiratory failures) requiring ICU admission and on mechanical ventilator support meeting inclusion and exclusion criteria The difference in the duration of mechanical ventilation in critically ill ventilated patients with liver cirrhosis when the nutritional therapy delivered as per estimated energy requirements versus measured requirements

Secondary Outcome Measures

Change in metabolic profile
The effect of nutritional therapy as per estimated energy requirements versus measured requirements in critically ill ventilated patients with liver cirrhosis on the Insulin resistance, ketone bodies, Non-esterified fatty acids (NEFA), amino acids profile and blood sugar levels would be studied
Change in inflammatory milieu
The effect of nutritional therapy as per estimated energy requirements versus measured requirements in critically ill ventilated patients with liver cirrhosis on the levels of interleukin 6 (IL-6), Tumor necrosis factor(TNF alfa), CRP(C reactive protein)would be studied
Change in clinical parameters
The effect of nutritional therapy as per estimated energy requirements versus measured requirements in critically ill ventilated patients with liver cirrhosis ondevelopment of new onset infection, resolution of sepsis, renal function and length of stay in the ICU/hospital would be studied
Change in ventilatory and arterial blood gas parameters
The effect of nutritional therapy as per estimated energy requirements versus measured requirements in critically ill ventilated patients with liver cirrhosis on ventilator parameters (FiO2, PEEP, PF ratio) and arterial blood gas parameters( PO2, PCO2, lactate, SpO2) would be studied
Change in nutritional parameters
The effect of nutritional therapy as per estimated energy requirements versus measured requirements in critically ill ventilated patients with liver cirrhosis on nutritional parameters( NUTRIC score, feed intolerance and would be studied
The association between energy metabolism, nutritional status and disease severity in patients with CLD
The association between energy metabolism (resting energy expenditure- REE, substrate utilization and macronutrient oxidation), nutritional status (by body composition and anthropometry)and disease severity in patients with CLD (CTP and MELD scores) would be studied

Full Information

First Posted
February 26, 2019
Last Updated
October 21, 2022
Sponsor
Institute of Liver and Biliary Sciences, India
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1. Study Identification

Unique Protocol Identification Number
NCT03871894
Brief Title
Indirect Calorimeter Based Study in Patients With Liver Cirrhosis
Acronym
METALIC
Official Title
Metabolic and Clinical Effects of Enteral Nutrition Therapy: Measured Versus Estimated Energy and Substrate Requirements in Critically Ill Cirrhotics-A Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
March 12, 2019 (Actual)
Primary Completion Date
August 31, 2022 (Actual)
Study Completion Date
August 31, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institute of Liver and Biliary Sciences, India

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Part I- Observational study In the first part , investigator would investigate and compare the energy requirements and substrate utilization in healthy subjects and in patients with liver cirrhosis of various etiologies across the disease severity state viz compensated, stable decompensated, critically ill cirrhotics. The investigator would also enroll patients with chronic kidney disease, critically ill patients of acute liver failure or acute on chronic liver failure as disease controls. Part II- Randomized Controlled Study All the eligible, critically ill cirrhotic patients on mechanical ventilator support would be randomized to a control group (receiving the nutritional therapy as per the standard enteral nutritional practice in a critical care setting) or the intervention group (receiving enteral nutrition based on proposed measured requirements by Indirect calorimetry (IC) given till the patient is in ICU(Intensive care unit). The IC would be done thrice a week in both groups.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Cirrhoses
Keywords
Indirect calorimeter, Resting energy expenditure, substrate utilization, nitrogen balance

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
83 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Control arm
Arm Type
Active Comparator
Arm Description
This is the group of critically ill cirrhotic patients on mechanical ventilator support who would receive the nutritional therapy as per the standard enteral nutritional practice in a critical care setting in cirrhotics till the period admitted in ICU(Intensive care unit) 35-40 Kcal/Kg IBW/day; 1.5g protein per kg per day.
Arm Title
Intervention arm
Arm Type
Experimental
Arm Description
This is the group of critically ill cirrhotic patients on mechanical ventilator support who would receive the nutritional therapy based on indirect calorimetry measurements till the period admitted in ICU(Intensive care unit); 1.5g protein per kg per day.
Intervention Type
Other
Intervention Name(s)
Indirect calorimetry based nutritional intervention till patient in ICU(Intensive care unit)
Intervention Description
Nutrition therapy based on measured energy expenditure by indirect calorimetry (IC) done alternate day till patient on ventilatory support and protein intake 1.5 g/kg IBW/day
Intervention Type
Other
Intervention Name(s)
Standard and fixed nutritional intervention till patient in ICU
Intervention Description
Fixed standard nutritional therapy 35-40 Kcal/Kg IBW/day and 1.5 g protein /Kg IBW/Day till patient on ventilator
Primary Outcome Measure Information:
Title
Part 1: An Observational study
Description
Study groups : Healthy controls Disease Groups Patients with liver cirrhosis (compensated and decompensated) Critically ill cirrhotics on mechanical ventilator support patients with chronic kidney disease (CKD) (stable,non dialyzed, non oliguric outpatients) Critically ill patients with Acute liver failure (ALF) on mechanical ventilator support Critically ill patients with Acute on chronic liver failure(ACLF) on mechanical ventilator support Severe acute pancreatitis on mechanical ventilator support Comparison of the prevalence of hyper and hypo metabolism in patients with chronic liver disease(CLD) and healthy controls and other disease groups.
Time Frame
One day (Observational)
Title
Part 2: A Randomized controlled trial
Description
Study group:Critically ill Cirrhotic: Diagnosed cases of liver cirrhosis with 2 or more organ failures (liver + renal/circulatory or respiratory failures) requiring ICU admission and on mechanical ventilator support meeting inclusion and exclusion criteria The difference in the duration of mechanical ventilation in critically ill ventilated patients with liver cirrhosis when the nutritional therapy delivered as per estimated energy requirements versus measured requirements
Time Frame
From date of enrollment until the date of ICU discharge /Leaving against medical advice, date of death from any cause, or off ventilatory support whichever comes first, assessed up to 28 days.
Secondary Outcome Measure Information:
Title
Change in metabolic profile
Description
The effect of nutritional therapy as per estimated energy requirements versus measured requirements in critically ill ventilated patients with liver cirrhosis on the Insulin resistance, ketone bodies, Non-esterified fatty acids (NEFA), amino acids profile and blood sugar levels would be studied
Time Frame
The metabolic parameters would be assessed at the baseline, Day 7 and at Day 15 of enrollment
Title
Change in inflammatory milieu
Description
The effect of nutritional therapy as per estimated energy requirements versus measured requirements in critically ill ventilated patients with liver cirrhosis on the levels of interleukin 6 (IL-6), Tumor necrosis factor(TNF alfa), CRP(C reactive protein)would be studied
Time Frame
The inflammatory markers would be assessed at the baseline, Day 7 and at Day 15 of enrollment
Title
Change in clinical parameters
Description
The effect of nutritional therapy as per estimated energy requirements versus measured requirements in critically ill ventilated patients with liver cirrhosis ondevelopment of new onset infection, resolution of sepsis, renal function and length of stay in the ICU/hospital would be studied
Time Frame
The clinical parameters would be assessed daily from the date of enrollment until the date of ICU discharge, date of death from any cause, or out of mechanical ventilatory support whichever comes first, assessed up to 28 days.
Title
Change in ventilatory and arterial blood gas parameters
Description
The effect of nutritional therapy as per estimated energy requirements versus measured requirements in critically ill ventilated patients with liver cirrhosis on ventilator parameters (FiO2, PEEP, PF ratio) and arterial blood gas parameters( PO2, PCO2, lactate, SpO2) would be studied
Time Frame
The ventilatory and arterial blood gas parameters would be assessed daily from the date of enrollment until the date of ICU discharge, date of death from any cause, or out of mechanical ventilatory support whichever comes first, assessed up to 28 days.
Title
Change in nutritional parameters
Description
The effect of nutritional therapy as per estimated energy requirements versus measured requirements in critically ill ventilated patients with liver cirrhosis on nutritional parameters( NUTRIC score, feed intolerance and would be studied
Time Frame
The nutritional parameters would be assesses at regular intervals maximum upto 28 days
Title
The association between energy metabolism, nutritional status and disease severity in patients with CLD
Description
The association between energy metabolism (resting energy expenditure- REE, substrate utilization and macronutrient oxidation), nutritional status (by body composition and anthropometry)and disease severity in patients with CLD (CTP and MELD scores) would be studied
Time Frame
one day (Observational)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Disease groups: • Patients with liver cirrhosis (diagnosis established based on routine clinical, biochemical and at least radiological, endoscopic or histological parameters.) admitted in Liver coma Intensive care unit and those admitted in ward. Disease controls: Patients with Acute liver failure (diagnosis established based on routine clinical, biochemical and at least radiological parameters) admitted in Liver coma Intensive care unit Patients with severe acute pancreatitis (diagnosis established based on routine clinical, biochemical and at least radiological parameters) admitted in Liver coma Intensive care unit Healthy Controls: Healthy subjects- Relatives of patients with no known chronic diseases (Chronic obstructive pulmonary disease, Coronary artery disease, Type 2 diabetes, Hypertension, Hypothyroidism, Koch's disease) or not on any long term medications. Patients with liver cirrhosis (diagnosis established based on routine clinical, biochemical and at least radiological, endoscopic or histological parameters.) admitted in Liver coma Intensive care unit who require mechanical ventilation Exclusion Criteria: Age<18 years Active upper gastrointestinal bleeding If there are conditions which precluded IC, such as an FiO2 >60 %, failure to cooperate, agitation, seizure activity, spasticity, or positive end-expiratory pressure (PEEP) >10 mmHg. Pregnant women Refused to consent/ inability to obtain informed consent. Known long standing diabetic If there is any evidence of medical/surgical instability Hepatocellular carcinoma Extrahepatic malignancies With persistent gastrointestinal dysfunction and ileus Patients who would be readmitted to the ICU Known long standing diabetic Terminally ill patients on high inotropic support Acute liver failure If there is any evidence of medical/surgical instability If patients are taking any portion of nutrition by mouth. Pregnant women Refused to consent/ inability to obtain informed consent. Patient on CRRT- continuous renal replacement therapy Severe co morbidities such as Chronic kidney disease requiring maintenance dialysis, COPD and Cardiac pathologies (Acute myocardial infarction, heart failure, ). Hepatocellular carcinoma Extrahepatic malignancies Moribund patient with likely survival <24 hours Patients enrolled in other drug trials.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jaya Benjamin, Msc,PhD
Organizational Affiliation
Institute of Liver and Biliary Sciences, sector D-1, Vasantkunj, New Delhi
Official's Role
Study Director
Facility Information:
Facility Name
ILBS
City
New Delhi
State/Province
Delhi
ZIP/Postal Code
110070
Country
India

12. IPD Sharing Statement

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Indirect Calorimeter Based Study in Patients With Liver Cirrhosis

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