Critical IllnessEFFORT-XNCT04261543
The Effect of High Protein and Early Resistance Exercise Versus Usual Care in Critically Ill Patients
A study testing High protein and early exercise in people with Critical Illness, run by University of Malaya at 1 site in Malaysia.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Critical Illness
- What is being tested?
- High protein and early exercise
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteMalaysia
- Study dates
- 5 Aug 2019to 9 Apr 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- >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)
Show all 16Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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
Read the 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.
- Conditions
- Critical Illness
- Being tested
- High protein and early exercise, Usual Care
- Keywords
- protein, exercise, muscle
- Medical subject headings
- Critical Illness, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High protein and early exerciseOther
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
Usual CareOther
Usual care group has protein prescription of ≤1.2 gram/kg body weight and exercise at the discretion of attending clinicians
| Study group | Role | What they receive |
|---|---|---|
| High Protein and Early Exercise | Experimental | 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 Receives: Other: High protein and early exercise |
| Usual Care | Active comparator | Usual care has a protein prescription of ≤1.2 gram/kg body weight and exercise prescription as per the discretion of attending clinicians Receives: Other: Usual Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rectus femoris cross-sectional area (RFCSA)
RFCSA measured by ultrasonography
Measured: Change in RFCSA between Day 1 and Day 10 of randomization
Rectus femoris cross-sectional area (RFCSA)
RFCSA measured by ultrasonography
Measured: Change in RFCSA between Day 1 of randomization and within 72 hours before discharge from the hospital
Rectus femoris linear depth (RF LD)
RF LD measured by ultrasonography
Measured: Change in RF LD between Day 1 and Day 10 of randomization
Rectus femoris linear depth (RF LD)
RF LD measured by ultrasonography
Measured: Change in RF LD between Day 1 of randomization and within 72 hours before discharge from the hospital
Secondary outcomes (16)
Quadriceps muscle echogenicity
Quadriceps muscle echogenicity measured by ultrasonography
Measured: Day 1 and Day 10 of randomization, and within 72 hours before discharge from the hospital
Quadriceps muscle pennation angle
Quadriceps muscle pennation angle measured by ultrasonography
Measured: Day 1 and Day 10 of randomization, and within 72 hours before discharge from the hospital
Quadriceps muscle fascicle length
Quadriceps muscle fascicle length measured by ultrasonography
Measured: Day 1 and Day 10 of randomization, and within 72 hours before discharge from the hospital
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
Measured: Day 1 of randomization (surrogate interview), within 72 hours before discharge from the ICU and hospital (by trained physiotherapist)
Short Physical Performance Batteries (SPPB)
An assessment that consist of balance test, gait speed test and chair stand test
Measured: Within 72 hours before discharge from the ICU and hospital
Handgrip strength
Handgrip strength of both hands by using handgrip dynamometer
Measured: Within 72 hours before discharge from the ICU and hospital
6 minutes walk test
To evaluate how far the subject can walk in 6 minutes time
Measured: Within 72 hours before discharge from the hospital
Manual muscle testing
Bilateral muscle strength for shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension and ankle dorsiflexion
Measured: Within 72 hours before discharge from the hospital
Knee extension strength
Knee extension strength measured by Handheld Dynamometer
Measured: Within 72 hours before discharge from the hospital
Mortality
Percentage of patient who died
Measured: Percentage of Patient who died within this ICU or hospital admission, at day 60 and 6 months post-randomization
Time-to-discharge alive from the hospital
Time-to-discharge alive from the hospital
Measured: Time elapsed from randomization to hospital discharge (for a maximum of 6 months from randomization)
Length of mechanical ventilation
Duration of mechanical ventilation
Measured: Total time from start to end of mechanical ventilation for a maximum of 6 months from randomization
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
Measured: 6 months after randomization
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
Measured: 6 months after randomization
Katz Activities of Daily Living (ADL)
Katz ADL is a questionnaire that will be administered by either surrogate or telephone interview
Measured: Day 1 of randomization (surrogate interview) and 6 months after randomization (telephone interview)
Lawton Instrumental Activities of Daily Living (IADL)
Lawton IADL is a questionnaire that will be administered by either surrogate or telephone interview
Measured: Day 1 of randomization (surrogate interview) and 6 months after randomization (telephone interview)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2020
- Study start5 Aug 2019
- Primary completion9 Oct 2023
- Study completion9 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Critical IllnessStudies of the same condition, open and under way.
- More trials run by University of MalayaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Malaya
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lee Zheng Yii, University of Malaya
- Investigators
- Zheng Yii Lee, Principal investigator, University of Malaya
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04261543
- Sponsor's protocol ID
- MREC ID NO: 20181115-6890
- Acronym
- EFFORT-X
- Status last verified
- Sep 2026
- First submitted
- 31 Jan 2020
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 21470008Heyland 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.
PubMed 26212171Arabi 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.
PubMed 28374096
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04261543
- Acronym / sponsor ID
- EFFORT-X / MREC ID NO: 20181115-6890
- Conditions
- Critical Illness
- Keywords
- protein, exercise, muscle
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- University of MalayaUniversity, hospital or other
- Study start
- 5 Aug 2019 (actual)
- Primary completion
- 9 Oct 2023 (actual)
- Study completion
- 9 Apr 2024 (actual)
- First posted
- 7 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High Protein and Early Exercise | Experimental | Other: High 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 |
| Usual Care | Active comparator | Other: Usual CareUsual care has a protein prescription of ≤1.2 gram/kg body weight and exercise prescription as per the discretion of attending clinicians |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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):
Key exclusion criteria (16 listed)
- >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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High protein and early exerciseHigh 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 | High Protein and Early Exercise |
| Usual CareUsual care group has protein prescription of ≤1.2 gram/kg body weight and exercise at the discretion of attending clinicians | Other | Usual Care |
Primary outcome
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
16 secondary outcomes
Quadriceps muscle echogenicity
Time frame: Day 1 and Day 10 of randomization, and within 72 hours before discharge from the hospital
Quadriceps muscle pennation angle
Time frame: Day 1 and Day 10 of randomization, and within 72 hours before discharge from the hospital
Quadriceps muscle fascicle length
Time frame: Day 1 and Day 10 of randomization, and within 72 hours before discharge from the hospital
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)
Short Physical Performance Batteries (SPPB)
Time frame: Within 72 hours before discharge from the ICU and hospital
Handgrip strength
Time frame: Within 72 hours before discharge from the ICU and hospital
6 minutes walk test
Time frame: Within 72 hours before discharge from the hospital
Manual muscle testing
Time frame: Within 72 hours before discharge from the hospital
Knee extension strength
Time frame: Within 72 hours before discharge from the hospital
Mortality
Time frame: Percentage of Patient who died within this ICU or hospital admission, at day 60 and 6 months post-randomization
Time-to-discharge alive from the hospital
Time frame: Time elapsed from randomization to hospital discharge (for a maximum of 6 months from randomization)
Length of mechanical ventilation
Time frame: Total time from start to end of mechanical ventilation for a maximum of 6 months from randomization
Health-related Quality of life by 36-item short form survey (SF-36)
Time frame: 6 months after randomization
Health-related Quality of life by Euro Quality of Life 5 Dimension 5 level (EQ-5D-5L)
Time frame: 6 months after randomization
Katz Activities of Daily Living (ADL)
Time frame: Day 1 of randomization (surrogate interview) and 6 months after randomization (telephone interview)
Lawton Instrumental Activities of Daily Living (IADL)
Time frame: Day 1 of randomization (surrogate interview) and 6 months after randomization (telephone interview)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2026.
- Background: PubMed 21470008Herridge 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.
- Background: PubMed 26212171Heyland 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.
- Background: PubMed 28374096Arabi 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zheng Yii Lee principal investigator
University of Malaya
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High protein and early exercise in people with Critical Illness, run by University of Malaya at 1 site in Malaysia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Malaysia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rectus femoris cross-sectional area (RFCSA) (time frame: Change in RFCSA between Day 1 and Day 10 of randomization). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04261543, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2026.