The Effect of High Protein and Early Resistance Exercise Versus Usual Care in Critically Ill Patients

Overview

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

Full Title of Study: “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

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: Single (Outcomes Assessor)
  • Study Primary Completion Date: August 5, 2021

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.

Interventions

  • Other: High protein and early exercise
    • 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
  • Other: Usual Care
    • Usual care group has protein prescription of ≤1.2 gram/kg body weight and exercise at the discretion of attending clinicians

Arms, Groups and Cohorts

  • Experimental: High Protein and Early Exercise
    • 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
  • Active Comparator: Usual Care
    • Usual care has a protein prescription of ≤1.2 gram/kg body weight and exercise prescription as per the discretion of attending clinicians

Clinical Trial Outcome Measures

Primary Measures

  • Rectus femoris cross-sectional area (RFCSA)
    • Time Frame: Change in RFCSA between Day 1 and Day 10 of randomization
    • RFCSA measured by ultrasonography
  • Rectus femoris cross-sectional area (RFCSA)
    • Time Frame: Change in RFCSA between Day 1 of randomization and within 72 hours before discharge from the hospital
    • RFCSA measured by ultrasonography
  • Rectus femoris linear depth (RF LD)
    • Time Frame: Change in RF LD between Day 1 and Day 10 of randomization
    • RF LD measured by ultrasonography
  • Rectus femoris linear depth (RF LD)
    • Time Frame: Change in RF LD between Day 1 of randomization and within 72 hours before discharge from the hospital
    • RF LD measured by ultrasonography

Secondary Measures

  • Quadriceps muscle echogenicity
    • Time Frame: Day 1 and Day 10 of randomization, and within 72 hours before discharge from the hospital
    • Quadriceps muscle echogenicity measured by ultrasonography
  • Quadriceps muscle pennation angle
    • Time Frame: Day 1 and Day 10 of randomization, and within 72 hours before discharge from the hospital
    • Quadriceps muscle pennation angle measured by ultrasonography
  • Quadriceps muscle fascicle length
    • Time Frame: Day 1 and Day 10 of randomization, and within 72 hours before discharge from the hospital
    • Quadriceps muscle fascicle length measured by ultrasonography
  • Functional Status Score for the Intensive Care Unit (FSS-ICU)
    • Time Frame: Day 1 of randomization (surrogate interview), within 72 hours before discharge from the ICU and hospital (by trained physiotherapist)
    • 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)
    • Time Frame: Within 72 hours before discharge from the ICU and hospital
    • An assessment that consist of balance test, gait speed test and chair stand test
  • Handgrip strength
    • Time Frame: Within 72 hours before discharge from the ICU and hospital
    • Handgrip strength of both hands by using handgrip dynamometer
  • 6 minutes walk test
    • Time Frame: Within 72 hours before discharge from the hospital
    • To evaluate how far the subject can walk in 6 minutes time
  • Manual muscle testing
    • Time Frame: Within 72 hours before discharge from the hospital
    • Bilateral muscle strength for shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension and ankle dorsiflexion
  • Knee extension strength
    • Time Frame: Within 72 hours before discharge from the hospital
    • Knee extension strength measured by Handheld Dynamometer
  • Mortality
    • Time Frame: Percentage of Patient who died within this ICU or hospital admission, at day 60 and 6 months post-randomization
    • Percentage of patient who died
  • Time-to-discharge alive from the hospital
    • Time Frame: Time elapsed from randomization to hospital discharge (for a maximum of 6 months from randomization)
    • Time-to-discharge alive from the hospital
  • Length of mechanical ventilation
    • Time Frame: Total time from start to end of mechanical ventilation for a maximum of 6 months from randomization
    • Duration of mechanical ventilation
  • Health-related Quality of life by 36-item short form survey (SF-36)
    • Time Frame: 6 months after randomization
    • 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)
    • Time Frame: 6 months after randomization
    • EQ-5D-5L is a questionnaire that will be administered by telephone interview
  • Katz Activities of Daily Living (ADL)
    • Time Frame: Day 1 of randomization (surrogate interview) and 6 months after randomization (telephone interview)
    • Katz ADL is a questionnaire that will be administered by either surrogate or telephone interview
  • Lawton Instrumental Activities of Daily Living (IADL)
    • Time Frame: Day 1 of randomization (surrogate interview) and 6 months after randomization (telephone interview)
    • Lawton IADL is a questionnaire that will be administered by either surrogate or telephone interview

Participating in This Clinical Trial

Inclusion Criteria

1. Age 18 years old and above 2. Mechanically ventilated and expected to remain mechanically ventilated for an additional 48 hours from screening 3. 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:

1. >96 continuous hours of mechanical ventilation before screening 2. Expected death or withdrawal of life-sustaining treatments within 7 days from screening 3. Pregnant (Note: post-partum and lactating patients are not excluded from the trial) 4. The responsible clinician feels that the patient either needs low or high protein 5. Patient requires parenteral nutrition only and site does not have products to reach the high protein dose group. 6. Not ambulating independently prior to illness that lead to ICU admission (use of gait aid permitted) 7. Lower extremity injury or impairments that prevents them walking prior to hospital discharge (e.g. amputation, knee/hip injury) 8. Pre-existing cognitive impairment or language barrier that prohibits outcomes assessment 9. Pre-existing primary severe systemic neuromuscular disease resulting in severe weakness pre-ICU (e.g., Guillain Barre) 10. Intracranial or spinal process affecting motor function 11. Patients in hospital >5 days prior to ICU admission 12. Not expected to stay ≥4 days after enrollment 13. Neuromuscular blocker infusion (eligible once infusion discontinued if other inclusion criteria met) 14. Lower extremity injury or impairments that prevents cycling (e.g. amputation, knee/hip injury) 15. Weight ≥150 kg 16. Physician declines enrolment for Exercise

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 90 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Malaya
  • Provider of Information About this Clinical Study
    • Principal Investigator: Lee Zheng Yii, Principal Investigator – University of Malaya
  • Overall Official(s)
    • Zheng Yii Lee, Principal Investigator, University of Malaya
  • Overall Contact(s)
    • Zheng Yii Lee, +60169754153, zheng_yii@hotmail.com

References

Herridge MS, Tansey CM, Matté 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.

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.

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. Review.

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