Clinical trial NCT04261543: The Effect of High Protein and Early Resistance Exercise Versus Usual Care in Critically Ill Patients
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
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Critical Illness
Keywords: protein
exercise
muscle
Lead sponsor: University of Malaya
Sponsor class: OTHER
First posted: 2020-02-07
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rectus femoris cross-sectional area (RFCSA)
timeFrame: Change in RFCSA between Day 1 and Day 10 of randomization
measure: Rectus femoris cross-sectional area (RFCSA)
timeFrame: Change in RFCSA between Day 1 of randomization and within 72 hours before discharge from the hospital
measure: Rectus femoris linear depth (RF LD)
timeFrame: Change in RF LD between Day 1 and Day 10 of randomization
measure: Rectus femoris linear depth (RF LD)
timeFrame: Change in RF LD between Day 1 of randomization and within 72 hours before discharge from the hospital
Secondary outcomes:
measure: Quadriceps muscle echogenicity
timeFrame: Day 1 and Day 10 of randomization, and within 72 hours before discharge from the hospital
measure: Quadriceps muscle pennation angle
timeFrame: Day 1 and Day 10 of randomization, and within 72 hours before discharge from the hospital
measure: Quadriceps muscle fascicle length
timeFrame: Day 1 and Day 10 of randomization, and within 72 hours before discharge from the hospital
measure: Functional Status Score for the Intensive Care Unit (FSS-ICU)
timeFrame: Day 1 of randomization (surrogate interview), within 72 hours before discharge from the ICU and hospital (by trained physiotherapist)
measure: Short Physical Performance Batteries (SPPB)
timeFrame: Within 72 hours before discharge from the ICU and hospital
measure: Handgrip strength
timeFrame: Within 72 hours before discharge from the ICU and hospital
measure: 6 minutes walk test
timeFrame: Within 72 hours before discharge from the hospital
measure: Manual muscle testing
timeFrame: Within 72 hours before discharge from the hospital
measure: Knee extension strength
timeFrame: Within 72 hours before discharge from the hospital
measure: Mortality
timeFrame: Percentage of Patient who died within this ICU or hospital admission, at day 60 and 6 months post-randomization
measure: Time-to-discharge alive from the hospital
timeFrame: Time elapsed from randomization to hospital discharge (for a maximum of 6 months from randomization)
measure: Length of mechanical ventilation
timeFrame: Total time from start to end of mechanical ventilation for a maximum of 6 months from randomization
measure: Health-related Quality of life by 36-item short form survey (SF-36)
timeFrame: 6 months after randomization
measure: Health-related Quality of life by Euro Quality of Life 5 Dimension 5 level (EQ-5D-5L)
timeFrame: 6 months after randomization
measure: Katz Activities of Daily Living (ADL)
timeFrame: Day 1 of randomization (surrogate interview) and 6 months after randomization (telephone interview)
measure: Lawton Instrumental Activities of Daily Living (IADL)
timeFrame: Day 1 of randomization (surrogate interview) and 6 months after randomization (telephone interview)
Other outcomes:
Locations:
city: Kuala Lumpur
country: Malaysia
facility: University of Malaya
Study officials:
affiliation: University of Malaya
name: Zheng Yii Lee
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.