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

Not Applicable
Active, not recruiting
Conditions
Critical Illness
Interventions
Other: Usual Care
Other: High protein and early exercise
Registration Number
NCT04261543
Lead Sponsor
University of Malaya
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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
120
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Usual CareUsual CareUsual care has a protein prescription of ≤1.2 gram/kg body weight and exercise prescription as per the discretion of attending clinicians
High Protein and Early ExerciseHigh protein and early exerciseHigh 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
Primary Outcome Measures
NameTimeMethod
Rectus femoris linear depth (RF LD)Change in RF LD between Day 1 of randomization and within 72 hours before discharge from the hospital

RF LD measured by ultrasonography

Rectus femoris cross-sectional area (RFCSA)Change in RFCSA between Day 1 of randomization and within 72 hours before discharge from the hospital

RFCSA measured by ultrasonography

Secondary Outcome Measures
NameTimeMethod
Short Physical Performance Batteries (SPPB)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 strengthWithin 72 hours before discharge from the ICU and hospital

Handgrip strength of both hands by using handgrip dynamometer

Quadriceps muscle echogenicityDay 1 and Day 10 of randomization, and within 72 hours before discharge from the hospital

Quadriceps muscle echogenicity measured by ultrasonography

6 minutes walk testWithin 72 hours before discharge from the hospital

To evaluate how far the subject can walk in 6 minutes time

Quadriceps muscle pennation angleDay 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 lengthDay 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)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

MortalityPercentage of Patient who died within this ICU or hospital admission, at day 60 and 6 months post-randomization

Percentage of patient who died

Length of mechanical ventilationTotal time from start to end of mechanical ventilation for a maximum of 6 months from randomization

Duration of mechanical ventilation

Manual muscle testingWithin 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 strengthWithin 72 hours before discharge from the hospital

Knee extension strength measured by Handheld Dynamometer

Health-related Quality of life by 36-item short form survey (SF-36)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)6 months after randomization

EQ-5D-5L is a questionnaire that will be administered by telephone interview

Time-to-discharge alive from the hospitalTime elapsed from randomization to hospital discharge (for a maximum of 6 months from randomization)

Time-to-discharge alive from the hospital

Katz Activities of Daily Living (ADL)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)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

Trial Locations

Locations (1)

University of Malaya

🇲🇾

Kuala Lumpur, Malaysia

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