Back to resultsThe Effect of High Protein and Early Resistance Exercise Versus Usual Care in Critically Ill Patients (EFFORT-X)
Primary Purpose
Critical Illness
Status
Recruiting
Phase
Not Applicable
Locations
Malaysia
Study Type
Interventional
Intervention
High protein and early exercise
Usual Care
Sponsored by
About this trial
This is an interventional prevention trial for Critical Illness focused on measuring protein, exercise, muscle
Eligibility Criteria
Inclusion Criteria:
- Age 18 years old and above
- Mechanically ventilated and expected to remain mechanically ventilated for an additional 48 hours from screening
High nutritional risk (at least one of the following):
- BMI ≤ 25 or ≥ 35
- Moderate to severe malnutrition as defined by Subjective Global Assessment (SGA)
- Frailty (Clinical Frailty Scale ≥ 5 from proxy)
- SARC-F (note: 'sarc-f' is the full name, not an abbreviation) questionnaire ≥ 4
- From point of screening, projected duration of mechanical ventilation of >4 days
Exclusion Criteria:
- >96 continuous hours of mechanical ventilation before screening
- Expected death or withdrawal of life-sustaining treatments within 7 days from screening
- Pregnant (Note: post-partum and lactating patients are not excluded from the trial)
- The responsible clinician feels that the patient either needs low or high protein
- Patient requires parenteral nutrition only and site does not have products to reach the high protein dose group.
- Not ambulating independently prior to illness that lead to ICU admission (use of gait aid permitted)
- Lower extremity injury or impairments that prevents them walking prior to hospital discharge (e.g. amputation, knee/hip injury)
- Pre-existing cognitive impairment or language barrier that prohibits outcomes assessment
- Pre-existing primary severe systemic neuromuscular disease resulting in severe weakness pre-ICU (e.g., Guillain Barre)
- Intracranial or spinal process affecting motor function
- Patients in hospital >5 days prior to ICU admission
- Not expected to stay ≥4 days after enrollment
- Neuromuscular blocker infusion (eligible once infusion discontinued if other inclusion criteria met)
- Lower extremity injury or impairments that prevents cycling (e.g. amputation, knee/hip injury)
- Weight ≥150 kg
- Physician declines enrolment for Exercise
Sites / Locations
- University of MalayaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
High Protein and Early Exercise
Usual Care
Arm Description
High protein is defined as a protein prescription of ≥2.2 gram/kg body weight; Early exercise is defined as exercise by using cycle ergometry for 45 minutes per day within 24 hours of randomization
Usual care has a protein prescription of ≤1.2 gram/kg body weight and exercise prescription as per the discretion of attending clinicians
Outcomes
Primary Outcome Measures
Rectus femoris cross-sectional area (RFCSA)
RFCSA measured by ultrasonography
Rectus femoris cross-sectional area (RFCSA)
RFCSA measured by ultrasonography
Rectus femoris linear depth (RF LD)
RF LD measured by ultrasonography
Rectus femoris linear depth (RF LD)
RF LD measured by ultrasonography
Secondary Outcome Measures
Quadriceps muscle echogenicity
Quadriceps muscle echogenicity measured by ultrasonography
Quadriceps muscle pennation angle
Quadriceps muscle pennation angle measured by ultrasonography
Quadriceps muscle fascicle length
Quadriceps muscle fascicle length measured by ultrasonography
Functional Status Score for the Intensive Care Unit (FSS-ICU)
An assessment that consist of rolling, transfer from supine to sit, sitting at the edge of bed, transfer from sit to stand and walking
Short Physical Performance Batteries (SPPB)
An assessment that consist of balance test, gait speed test and chair stand test
Handgrip strength
Handgrip strength of both hands by using handgrip dynamometer
6 minutes walk test
To evaluate how far the subject can walk in 6 minutes time
Manual muscle testing
Bilateral muscle strength for shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension and ankle dorsiflexion
Knee extension strength
Knee extension strength measured by Handheld Dynamometer
Mortality
Percentage of patient who died
Time-to-discharge alive from the hospital
Time-to-discharge alive from the hospital
Length of mechanical ventilation
Duration of mechanical ventilation
Health-related Quality of life by 36-item short form survey (SF-36)
SF-36 is a questionnaire that will be administered by telephone interview
Health-related Quality of life by Euro Quality of Life 5 Dimension 5 level (EQ-5D-5L)
EQ-5D-5L is a questionnaire that will be administered by telephone interview
Katz Activities of Daily Living (ADL)
Katz ADL is a questionnaire that will be administered by either surrogate or telephone interview
Lawton Instrumental Activities of Daily Living (IADL)
Lawton IADL is a questionnaire that will be administered by either surrogate or telephone interview
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04261543
Brief Title
The Effect of High Protein and Early Resistance Exercise Versus Usual Care in Critically Ill Patients
Acronym
EFFORT-X
Official Title
The Effect of High Protein and Early Resistance Exercise Versus Usual Care on Muscle Mass, Strength and Quality, Clinical Outcomes, Functional Outcomes and Quality of Life in Mechanically Ventilated Critically Ill Patients
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 5, 2019 (Actual)
Primary Completion Date
February 5, 2024 (Anticipated)
Study Completion Date
December 5, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Malaya
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
This is a 2-arm, parallel-group, randomized controlled trial that investigates the effect of combined high protein and early resistance exercise versus usual care on muscle mass, quality and strength, clinical outcomes, functional outcomes and quality of life in mechanically ventilated critically ill patients
Detailed Description
With the advancement of critical care, about 80% of ICU patients are surviving critical illness. However, ICU survivors often experience significant post-ICU morbidities including muscle weakness and impairments in physical functioning that can persist for years. We hypothesized that early intervention with two of the most basic features of critical care: nutrition (feeding high protein) together with mobility (early resistance exercise) may help to attenuate muscle loss, thereby reducing the severity of ICU-acquired weakness and its associated physical impairments. A 2-arm, parallel-group, randomized controlled trial is proposed to investigate the effect of the combined interventions. The intervention will be conducted for up to 28 days in the ICU. Outcome measurements will be conducted by a blinded assessor at baseline (within 24 hours of randomization), Day 10 post-randomization, before hospital discharge and at 6-month post-randomization. Ultrasound and bioelectrical impedance analysis will be conducted to measure muscle mass and quality. Manual muscle testing, handgrip and knee extension strength will also be measured. Physical function will be assessed by a series of test including the six minutes walk test. Telephone interview will be conducted to administer quality of life questionnaires at 6 months. These combined simple and non-invasive interventions, if proven effective, may potentially revolutionize critical care.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Critical Illness
Keywords
protein, exercise, muscle
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
High Protein and Early Exercise
Arm Type
Experimental
Arm Description
High protein is defined as a protein prescription of ≥2.2 gram/kg body weight; Early exercise is defined as exercise by using cycle ergometry for 45 minutes per day within 24 hours of randomization
Arm Title
Usual Care
Arm Type
Active Comparator
Arm Description
Usual care has a protein prescription of ≤1.2 gram/kg body weight and exercise prescription as per the discretion of attending clinicians
Intervention Type
Other
Intervention Name(s)
High protein and early exercise
Intervention Description
High protein is defined as protein prescription of ≥2.2 gram/kg body weight and early exercise is defined as starting cycle ergometry intervention within 24 hours of randomization
Intervention Type
Other
Intervention Name(s)
Usual Care
Intervention Description
Usual care group has protein prescription of ≤1.2 gram/kg body weight and exercise at the discretion of attending clinicians
Primary Outcome Measure Information:
Title
Rectus femoris cross-sectional area (RFCSA)
Description
RFCSA measured by ultrasonography
Time Frame
Change in RFCSA between Day 1 and Day 10 of randomization
Title
Rectus femoris cross-sectional area (RFCSA)
Description
RFCSA measured by ultrasonography
Time Frame
Change in RFCSA between Day 1 of randomization and within 72 hours before discharge from the hospital
Title
Rectus femoris linear depth (RF LD)
Description
RF LD measured by ultrasonography
Time Frame
Change in RF LD between Day 1 and Day 10 of randomization
Title
Rectus femoris linear depth (RF LD)
Description
RF LD measured by ultrasonography
Time Frame
Change in RF LD between Day 1 of randomization and within 72 hours before discharge from the hospital
Secondary Outcome Measure Information:
Title
Quadriceps muscle echogenicity
Description
Quadriceps muscle echogenicity measured by ultrasonography
Time Frame
Day 1 and Day 10 of randomization, and within 72 hours before discharge from the hospital
Title
Quadriceps muscle pennation angle
Description
Quadriceps muscle pennation angle measured by ultrasonography
Time Frame
Day 1 and Day 10 of randomization, and within 72 hours before discharge from the hospital
Title
Quadriceps muscle fascicle length
Description
Quadriceps muscle fascicle length measured by ultrasonography
Time Frame
Day 1 and Day 10 of randomization, and within 72 hours before discharge from the hospital
Title
Functional Status Score for the Intensive Care Unit (FSS-ICU)
Description
An assessment that consist of rolling, transfer from supine to sit, sitting at the edge of bed, transfer from sit to stand and walking
Time Frame
Day 1 of randomization (surrogate interview), within 72 hours before discharge from the ICU and hospital (by trained physiotherapist)
Title
Short Physical Performance Batteries (SPPB)
Description
An assessment that consist of balance test, gait speed test and chair stand test
Time Frame
Within 72 hours before discharge from the ICU and hospital
Title
Handgrip strength
Description
Handgrip strength of both hands by using handgrip dynamometer
Time Frame
Within 72 hours before discharge from the ICU and hospital
Title
6 minutes walk test
Description
To evaluate how far the subject can walk in 6 minutes time
Time Frame
Within 72 hours before discharge from the hospital
Title
Manual muscle testing
Description
Bilateral muscle strength for shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension and ankle dorsiflexion
Time Frame
Within 72 hours before discharge from the hospital
Title
Knee extension strength
Description
Knee extension strength measured by Handheld Dynamometer
Time Frame
Within 72 hours before discharge from the hospital
Title
Mortality
Description
Percentage of patient who died
Time Frame
Percentage of Patient who died within this ICU or hospital admission, at day 60 and 6 months post-randomization
Title
Time-to-discharge alive from the hospital
Description
Time-to-discharge alive from the hospital
Time Frame
Time elapsed from randomization to hospital discharge (for a maximum of 6 months from randomization)
Title
Length of mechanical ventilation
Description
Duration of mechanical ventilation
Time Frame
Total time from start to end of mechanical ventilation for a maximum of 6 months from randomization
Title
Health-related Quality of life by 36-item short form survey (SF-36)
Description
SF-36 is a questionnaire that will be administered by telephone interview
Time Frame
6 months after randomization
Title
Health-related Quality of life by Euro Quality of Life 5 Dimension 5 level (EQ-5D-5L)
Description
EQ-5D-5L is a questionnaire that will be administered by telephone interview
Time Frame
6 months after randomization
Title
Katz Activities of Daily Living (ADL)
Description
Katz ADL is a questionnaire that will be administered by either surrogate or telephone interview
Time Frame
Day 1 of randomization (surrogate interview) and 6 months after randomization (telephone interview)
Title
Lawton Instrumental Activities of Daily Living (IADL)
Description
Lawton IADL is a questionnaire that will be administered by either surrogate or telephone interview
Time Frame
Day 1 of randomization (surrogate interview) and 6 months after randomization (telephone interview)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 18 years old and above
Mechanically ventilated and expected to remain mechanically ventilated for an additional 48 hours from screening
High nutritional risk (at least one of the following):
BMI ≤ 25 or ≥ 35
Moderate to severe malnutrition as defined by Subjective Global Assessment (SGA)
Frailty (Clinical Frailty Scale ≥ 5 from proxy)
SARC-F (note: 'sarc-f' is the full name, not an abbreviation) questionnaire ≥ 4
From point of screening, projected duration of mechanical ventilation of >4 days
Exclusion Criteria:
>96 continuous hours of mechanical ventilation before screening
Expected death or withdrawal of life-sustaining treatments within 7 days from screening
Pregnant (Note: post-partum and lactating patients are not excluded from the trial)
The responsible clinician feels that the patient either needs low or high protein
Patient requires parenteral nutrition only and site does not have products to reach the high protein dose group.
Not ambulating independently prior to illness that lead to ICU admission (use of gait aid permitted)
Lower extremity injury or impairments that prevents them walking prior to hospital discharge (e.g. amputation, knee/hip injury)
Pre-existing cognitive impairment or language barrier that prohibits outcomes assessment
Pre-existing primary severe systemic neuromuscular disease resulting in severe weakness pre-ICU (e.g., Guillain Barre)
Intracranial or spinal process affecting motor function
Patients in hospital >5 days prior to ICU admission
Not expected to stay ≥4 days after enrollment
Neuromuscular blocker infusion (eligible once infusion discontinued if other inclusion criteria met)
Lower extremity injury or impairments that prevents cycling (e.g. amputation, knee/hip injury)
Weight ≥150 kg
Physician declines enrolment for Exercise
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zheng Yii Lee
Phone
+60169754153
Email
zheng_yii@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zheng Yii Lee
Organizational Affiliation
University of Malaya
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Malaya
City
Kuala Lumpur
ZIP/Postal Code
50603
Country
Malaysia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lee Zheng Yii
Phone
+60169754153
Email
zheng_yii@hotmail.com
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
21470008
Citation
Herridge MS, Tansey CM, Matte A, Tomlinson G, Diaz-Granados N, Cooper A, Guest CB, Mazer CD, Mehta S, Stewart TE, Kudlow P, Cook D, Slutsky AS, Cheung AM; Canadian Critical Care Trials Group. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med. 2011 Apr 7;364(14):1293-304. doi: 10.1056/NEJMoa1011802.
Results Reference
background
PubMed Identifier
26212171
Citation
Heyland DK, Stapleton RD, Mourtzakis M, Hough CL, Morris P, Deutz NE, Colantuoni E, Day A, Prado CM, Needham DM. Combining nutrition and exercise to optimize survival and recovery from critical illness: Conceptual and methodological issues. Clin Nutr. 2016 Oct;35(5):1196-206. doi: 10.1016/j.clnu.2015.07.003. Epub 2015 Jul 16.
Results Reference
background
PubMed Identifier
28374096
Citation
Arabi YM, Casaer MP, Chapman M, Heyland DK, Ichai C, Marik PE, Martindale RG, McClave SA, Preiser JC, Reignier J, Rice TW, Van den Berghe G, van Zanten ARH, Weijs PJM. The intensive care medicine research agenda in nutrition and metabolism. Intensive Care Med. 2017 Sep;43(9):1239-1256. doi: 10.1007/s00134-017-4711-6. Epub 2017 Apr 3.
Results Reference
background
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The Effect of High Protein and Early Resistance Exercise Versus Usual Care in Critically Ill Patients
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