Acute Respiratory FailurePhase 2NEXISNCT03021902

Nutrition and Exercise in Critical Illness

A Phase 2 study testing IV amino acids and In-bed cycle ergometry exercise in people with Acute Respiratory Failure, run by Clinical Evaluation Research Unit at Kingston General Hospital at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Acute Respiratory Failure
What is being tested?: IV amino acids and In-bed cycle ergometry exercise
Type of treatment: Injection or infusion, Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 115 participants
Where: 7 sitesUnited States
Study dates: 28 Sep 2017to 23 Jun 2025
Phase: Phase 2
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

≥18 years old.
Requiring mechanical ventilation with actual or expected total duration of mechanical ventilation ≥ 48 hours.
Expected ICU stay ≥ 4 days after enrollment (to permit adequate exposure to the proposed intervention).

Who cannot join

>96 continuous hours of mechanical ventilation before enrollment.
Expected death or withdrawal of life-sustaining treatments within this hospitalization.
No expectation for any nutritional intake within the subsequent 72 hours.
Severe chronic liver disease (MELD score ≥20) or acute fulminant hepatitis.
Documented allergy to the amino acid intervention.
Metabolic disorders involving impaired nitrogen utilization

Show all 23Show fewer

Not ambulating independently prior to illness that lead to ICU admission (use of gait aid permitted).
Pre-existing primary systemic neuromuscular disease (e.g. Guillain Barre).
Neuromuscular blocker infusion (eligible once infusion discontinued if other inclusion criteria met).
Intracranial or spinal process affecting motor function
Pre-existing cognitive impairment or language barrier that prohibits outcomes assessment.
Patients in hospital >5 days prior to ICU admission
Lower extremity impairments that prevent cycling (e.g. amputation, knee/hip injury).
Remaining intubated for airway protection only
Weight ≥150kg
Physician declines patient enrollment
Insufficient IV access
Pregnant
Incarcerated
Patients with acute kidney injury (AKI) as defined by meeting any of the KDIGO criteria (below) and not receiving renal replacement therapy:
Increase in serum creatinine by ≥ 0.3 mg/dl within 48 hours or
Increase in serum creatinine to ≥ 1.5 times baseline** or
Urine volume <0.5 ml/kg/h for 6 hoursⴕ

Trial locations and contacts

7 sites in 1 country.

City, postcode or hospital

7 sites in 1 country

United States7 sites

Johns Hopkins Hospital
Baltimore, Maryland, 21287
University of Vermont College of Medicine
Burlington, Vermont, 05405
University of Kentucky
Lexington, Kentucky, 40506
Oregon Health & Science University
Portland, Oregon, 97239
Harborview Medical Center
Seattle, Washington, 98104
Montefiore Albert Einstein College of Medicine
The Bronx, New York, 10467
Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: Nutrition and Exercise in Critical Illness (The NEXIS Trial): A Randomized Trial of Combined Cycle Ergometry and Amino Acids in the ICU

This study proposes a novel early intervention combining Intravenous (IV) amino acids plus in-bed cycle ergometry exercise to improve physical outcomes in critically ill patients. The investigators hypothesize that this innovative approach will improve short-term physical functioning outcomes (primary outcome), as well as amino acid metabolism, body composition, and patient-reported outcomes at 6-month follow-up.

Read the detailed description

The evaluation of a combination of exercise and protein supplementation in intensive care unit (ICU) patients is novel and potentially very important. For instance, outside of the ICU, in other clinical conditions, the combination of protein supplementation and exercise improves protein synthesis, muscle mass, and muscle strength compared to protein or exercise alone.[63-70] Hence, an opportunity exists to improve ICU patients' physical outcomes via evaluating the combination of optimized protein intake and early exercise in the ICU setting.

The proposed intervention and hypothesis: The investigators propose a multi-centered Phase II RCT, with blinded outcomes assessment, of a combination of intravenous (IV) amino acid supplementation and early in-bed cycle ergometry exercise versus usual care in ICU patients requiring mechanical ventilation. The investigators hypothesize that this novel combined intervention will: (1) improve physical functioning at hospital discharge; (2) reduce muscle wasting with improved amino acid metabolism and protein synthesis in-hospital; and (3) improve health-related quality of life, physical functioning, and healthcare resource utilization at 6 months after enrollment. Preliminary data show feasibility and safety of IV amino acids and the proposed exercise intervention. The investigators have chosen a primary outcome that correlates well with long-term outcomes including mortality, hospitalization, and quality of life. [54] If this Phase II trial is positive, investigators will seek funding for a Phase III RCT to demonstrate sustained improvements with a longer-term patient-centered primary outcome and to examine the feasibility, and facilitators/barriers of delivery of this intervention by ICU nurses, physical therapists, and others. If proven effective, this combined intervention has potential to revolutionize care of ICU patients and have a major public health impact on the growing number of ICU survivors.

Objectives: To demonstrate that the innovative combination of amino acid supplementation plus early in-bed cycle ergometry exercise improves physical outcomes of ICU patients.

Specific Aims of Full Phase II RCT:

Short-term performance-based physical function outcomes. To determine if a combined IV amino acid supplementation and in-bed cycle ergometry exercise intervention, compared to usual care, improves in hospital muscle strength and performance-based physical functioning outcomes in critically ill patients, using a primary endpoint of six-minute walk distance (6MWD) at hospital discharge.
Body composition. To determine if the combined intervention, compared to usual care, improves amino acid utilization and decreases muscle wasting in ICU patients (secondary endpoints).
Patient-reported outcomes and health care utilization at 6 months. To determine if the combined intervention, compared to usual care, improves physical functioning, health-related quality of life, and healthcare utilization at 6 months after study enrollment (secondary endpoints).

NEXIS Flame mechanisitic Ancillary sub study:

In the proposed sub-study, the addition of bronchoaveloar lavages, blood sampling and muscle sampling measures during the participant's ICU stay will provide the ability to examine the effects of the NEXIS intervention on inflammation as a possible mechanism for improved muscle weakness.

Specific Aims of the NEXIS FLAME mechanistic ancillary study:

To determine if the NEXIS intervention attenuates the release of IL-17 and related cytokines to reduce systemic inflammation in humans.
To determine if the NEXIS intervention reduces lung injury and neutrophilic lung inflammation in humans.
To determine if the NEXIS intervention attenuates skeletal muscle fiber atrophy via down regulation of muscle proteolytic pathways.
To determine if the NEXIS intervention, and exercise specifically, reduces the content of inflammatory cells in skeletal muscle.

Conditions: Acute Respiratory Failure
Being tested: IV amino acids, In-bed cycle ergometry exercise

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

IV amino acidsDrug
Also called Clinisol 15% (Baxter) - sulfite-free (Amino Acid) Injection
IV amino acids delivered by continuous infusion, such that the total enteral and IV protein will be between 2.0-2.5 g/kg/day as a combination of amino acid infusion plus standard feeding.
In-bed cycle ergometry exerciseDevice
Also called MotoMed Letto II Cycle Ergometer
In-bed cycle ergometry exercise delivered in 45-minute sessions once-daily 5 days per week according to a detailed specific protocol that includes a safety check in combination with vigorous verbal encouragement from trained research staff delivering the intervention to promote active cycling.
Cycling is protocolized to provide graduated increases in resistance during each session and between daily sessions. Cycling will continue through ICU discharge or 21 calendar days after randomization. The intervention will specifically occur during ICU stay.

Study groups in NCT03021902
Study group	Role	What they receive
IV amino acid + in-bed cycle ergometry	Experimental	Beginning within 96 hours of initiation of mechanical ventilation, participants will receive the combined intervention that includes IV amino acids supplementation and in-bed cycle ergometry exercise Receives: Drug: IV amino acids; Device: In-bed cycle ergometry exercise
Usual care	No intervention	Participants randomized to the usual care arm will receive usual care protein and exercise.

What is being measured

The primary outcome is the main question the study is designed to answer.

Physical functioning
6-minute walk distance
Measured: Hospital discharge (up to 26 weeks after randomization)

Secondary outcomes (34)

Overall strength-upper extremity
MRC Sum-score (Medical Research Council (MRC) Scale for Muscle Strength). Subscales scored 0-5, where 5 is normal. Total score is the sum of the 6 upper extremity subscales.
Measured: Hospital discharge (up to 26 weeks after randomization)
Overall strength-lower extremity
MRC Sum-score (Medical Research Council (MRC) Scale for Muscle Strength). Subscales scored 0-5, where 5 is normal. Total score is the sum of the 6 lower extremity subscales.
Measured: Hospital discharge (up to 26 weeks after randomization)
Quadriceps force-lower extremity strength
Hand held dynamometry
Measured: Hospital discharge (up to 26 weeks after randomization)
Distal strength-hand grip strength
Hand held dynamometry
Measured: ICU and hospital discharge (up to 26 weeks after randomization)
Overall Physical Functional status - Short Physical Performance Battery
Short Physical Performance Battery
Measured: ICU and hospital discharge (up to 26 weeks after randomization)
Overall Physical Functional status - Functional Status Score - ICU
Functional Status Score - ICU 5 items are performed: rolling, transfer from supine to sit, sitting at the edge of bed, transfer from sit to stand, and walking Each task is evaluated using an eight-point ordinal scale ranging from 0 (unable to perform) to 7 (complete independence) Item scores are summed The total score ranges from 0-35, with higher scores indicating better physical functioning.
Measured: ICU and hospital discharge (up to 26 weeks after randomization)
Mortality
Chart review
Measured: ICU and hospital discharge (up to 26 weeks after randomization)
Length of ventilation
Chart review
Measured: ICU and hospital discharge (up to 26 weeks after randomization)
ICU stay
Chart review
Measured: ICU and hospital discharge (up to 26 weeks after randomization)
Hospital stay
Chart review
Measured: ICU and hospital discharge (up to 26 weeks after randomization)
ICU readmission
Chart review
Measured: Hospital discharge (up to 26 weeks after randomization)
Re-intubation
Chart review
Measured: Hospital discharge (up to 26 weeks after randomization)
Hospital-acquired infections
Chart review
Measured: Hospital discharge (up to 26 weeks after randomization)
Discharge location (e.g. home vs. rehab)
Chart review
Measured: Hospital discharge (up to 26 weeks after randomization)
Body composition - Ultrasound
Ultrasound of quadriceps
Measured: Enrollment, hospital discharge, & ICU discharge (up to 26 weeks after randomization)
Body composition - CT - Chest when clinically available
Chest CT
Measured: Enrollment, hospital discharge, & ICU discharge (up to 26 weeks after randomization)
Body composition - CT - Abdominal Scan when clinically available
Abdominal CT scan at 3rd lumbar vertebra
Measured: Enrollment, hospital discharge, & ICU discharge (up to 26 weeks after randomization)
Health-related quality of life - SF-36
36-Item Short Form Health Survey (SF-36) All items are scored so that a high score defines a more favorable health state.
Each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100 Items in the same scale are averaged together to create the 8 scale scores. Items that are left blank (missing data) are not taken into account when calculating the scale scores.
Scale scores represent the average for all items in the scale that the respondent answered.
Measured: Telephone survey at 6 months
Health-related quality of life - EQ-5D-5L
EuroQol Group standardized measure of health status (EQ-5D-5L)
Measured: Telephone survey at 6 months
Physical functioning - Katz ADL
Katz Index of Independence in Activities of Daily Living (Katz ADL) Total score where 6 = High (patient independent) 0 = Low (patient very dependent)
Measured: Hospital discharge (proxy) and telephone survey at 6 months
Physical functioning - Lawton IADL
Lawton Instrument Activities of Daily Living Scale (Lawton IADL) A summary score ranges from 0 (low function, dependent) to 8 (high function, independent) for women and 0 through 5 for men to avoid potential gender bias.
Measured: Telephone survey at 6 months
Physical functioning/participation - return to work
Return to baseline work/activity
Measured: Telephone survey at 6 months
Physical functioning/participation - living location
Living location
Measured: Telephone survey at 6 months
Mental and Cognitive Functioning - MoCA-BLIND
MoCA-BLIND The total possible score is 22 points; a score of 18 or above is considered normal
Measured: Telephone survey at 6 months
Mental and Cognitive Functioning - HADS
Hospital Anxiety and Depression Scale The HADS questionnaire has seven items each for depression and anxiety subscales. Scoring for each item ranges from zero to three, with three denoting highest anxiety or depression level. A total subscale score of >8 points out of a possible 21 denotes considerable symptoms of anxiety or depression.
Measured: Telephone survey at 6 months
Mental and Cognitive Functioning - IES-R
Impact of Events Scale Scoring for each item ranges from 0-4 Total score ranges from 0-88, where a total score of 33 or over signifies the likely presence of PTSD
Measured: Telephone survey at 6 months
Health Care Resource Utilization
Admission to ICU, hospital, rehabilitation \& nursing facility
Measured: Telephone survey at 6 months
Body composition - DEXA Scan
Whole Body DEXA Scan
Measured: At Hospital Discharge
Body Composition - Heavy water
Fat-free and fat mass can be measured with D2O in body fluids using gas chromatography-tandem mass spectrometry.
Measured: Enrollment, Days 1-7
Plasma and muscle protein synthesis - Heavy water
Muscle protein synthesis will be analyzed with chromatography and mass spectrometry techniques.
Measured: Enrollment, Days 1-7
NEXIS FLAME - Circulating inflammatory mediators
Blood IL-17, IL-23, IL-6, TNFα, CXCK1, CXCL5, CXCL8, CCL2, SP-D, KL-6, vWF, and leukocyte counts with differential
Measured: Enrollment, Days 3, 5, and 8
NEXIS FLAME - Lung Inflammation
Bronchoalveolar lavage neutrophil counts, IL-17A, CXCL5, and protein
Measured: Enrollment, Day 5
NEXIS FLAME - Muscle area
Single muscle fiber cross-sectional area (CSA), UPS expression, MuRF1 expression, myosin protein content (all from vastus lateralis sampling)
Measured: Enrollment, Day 5
NEXIS FLAME - Muscle inflammation
Muscle macrophages (CD45+, CD206+)
Measured: Enrollment, Day 5

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Sep 201723 Jun 2025

First posted16 Jan 2017 (estimated)
Study start28 Sep 2017
Primary completion14 Jan 2025
Study completion23 Jun 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (12)Papers the sponsor has linked to this study.
Other trials for Acute Respiratory FailureStudies of the same condition, open and under way.
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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind
Who is masked: Outcomes assessor
Enrolment: 115 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03021902
Sponsor's protocol ID: The NEXIS Trial
Acronym: NEXIS
Status last verified: Aug 2025
First submitted: 21 Dec 2016
Last updated: 27 Aug 2025
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: Yes
Individual data sharing: No: There is no plan to share IPD.

Publications

Burtin C, Clerckx B, Robbeets C, Ferdinande P, Langer D, Troosters T, Hermans G, Decramer M, Gosselink R. Early exercise in critically ill patients enhances short-term functional recovery. Crit Care Med. 2009 Sep;37(9):2499-505. doi: 10.1097/CCM.0b013e3181a38937.
PubMed 19623052
Chan KS, Pfoh ER, Denehy L, Elliott D, Holland AE, Dinglas VD, Needham DM. Construct validity and minimal important difference of 6-minute walk distance in survivors of acute respiratory failure. Chest. 2015 May;147(5):1316-1326. doi: 10.1378/chest.14-1808.
PubMed 25742048
Kho ME, Truong AD, Zanni JM, Ciesla ND, Brower RG, Palmer JB, Needham DM. Neuromuscular electrical stimulation in mechanically ventilated patients: a randomized, sham-controlled pilot trial with blinded outcome assessment. J Crit Care. 2015 Feb;30(1):32-9. doi: 10.1016/j.jcrc.2014.09.014. Epub 2014 Sep 22.
PubMed 25307979
Heyland D, Muscedere J, Wischmeyer PE, Cook D, Jones G, Albert M, Elke G, Berger MM, Day AG; Canadian Critical Care Trials Group. A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med. 2013 Apr 18;368(16):1489-97. doi: 10.1056/NEJMoa1212722.
PubMed 23594003
National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network; Rice TW, Wheeler AP, Thompson BT, Steingrub J, Hite RD, Moss M, Morris A, Dong N, Rock P. Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. JAMA. 2012 Feb 22;307(8):795-803. doi: 10.1001/jama.2012.137. Epub 2012 Feb 5.
PubMed 22307571
National Heart, Lung, and Blood Institute ARDS Clinical Trials Network; Truwit JD, Bernard GR, Steingrub J, Matthay MA, Liu KD, Albertson TE, Brower RG, Shanholtz C, Rock P, Douglas IS, deBoisblanc BP, Hough CL, Hite RD, Thompson BT. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med. 2014 Jun 5;370(23):2191-200. doi: 10.1056/NEJMoa1401520. Epub 2014 May 18.
PubMed 24835849
Parry SM, Berney S, Koopman R, Bryant A, El-Ansary D, Puthucheary Z, Hart N, Warrillow S, Denehy L. Early rehabilitation in critical care (eRiCC): functional electrical stimulation with cycling protocol for a randomised controlled trial. BMJ Open. 2012 Sep 13;2(5):e001891. doi: 10.1136/bmjopen-2012-001891. Print 2012.
PubMed 22983782
Fan E, Zanni JM, Dennison CR, Lepre SJ, Needham DM. Critical illness neuromyopathy and muscle weakness in patients in the intensive care unit. AACN Adv Crit Care. 2009 Jul-Sep;20(3):243-53. doi: 10.1097/NCI.0b013e3181ac2551.
PubMed 19638746
Dowdy DW, Dinglas V, Mendez-Tellez PA, Bienvenu OJ, Sevransky J, Dennison CR, Shanholtz C, Needham DM. Intensive care unit hypoglycemia predicts depression during early recovery from acute lung injury. Crit Care Med. 2008 Oct;36(10):2726-33. doi: 10.1097/CCM.0b013e31818781f5.
PubMed 18766087
Needham DM, Files DC, Hough CL, Mayer KP, Ardren S, Fatima A, Jiang X, Day AG, Dinglas VD, Hiser SL, Kiyatkin ME, Khan A, Morris PE, Carson SS, Antkowiak M, Bakhru RN, Burns S, Nath SD, Gibbs KW, Gundel SJ, Kalema AG, Sturgill JL, Ventrone S, Heyland DK, Stapleton RD; With The NEXIS Study Team. Nutrition and Exercise in Critical Illness (NEXIS) trial: randomized trial of combined in-bed cycling and intravenous amino acid plus usual care. Am J Respir Crit Care Med. 2026 Jul 13:aamag287. doi: 10.1093/ajrccm/aamag287. Online ahead of print.
PubMed 42438140
Al-Dorzi HM, Stapleton RD, Arabi YM. Nutrition priorities in obese critically ill patients. Curr Opin Clin Nutr Metab Care. 2022 Mar 1;25(2):99-109. doi: 10.1097/MCO.0000000000000803.
PubMed 34930871
Heyland DK, Day A, Clarke GJ, Hough CT, Files DC, Mourtzakis M, Deutz N, Needham DM, Stapleton R. Nutrition and Exercise in Critical Illness Trial (NEXIS Trial): a protocol of a multicentred, randomised controlled trial of combined cycle ergometry and amino acid supplementation commenced early during critical illness. BMJ Open. 2019 Jul 31;9(7):e027893. doi: 10.1136/bmjopen-2018-027893.
PubMed 31371287

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 27 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Nutrition and Exercise in Critical Illness (The NEXIS Trial): A Randomized Trial of Combined Cycle Ergometry and Amino Acids in the ICU
ClinicalTrials.gov ID: NCT03021902
Acronym / sponsor ID: NEXIS / The NEXIS Trial
Conditions: Acute Respiratory Failure
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 115 participants (actual)
Lead sponsor: Clinical Evaluation Research Unit at Kingston General HospitalUniversity, hospital or other
Collaborators: University of Vermont, Johns Hopkins University
Study start: 28 Sep 2017 (actual)
Primary completion: 14 Jan 2025 (actual)
Study completion: 23 Jun 2025 (actual)
First posted: 16 Jan 2017 (estimated)
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.

Detailed description

Objectives: To demonstrate that the innovative combination of amino acid supplementation plus early in-bed cycle ergometry exercise improves physical outcomes of ICU patients.

Specific Aims of Full Phase II RCT:

Short-term performance-based physical function outcomes. To determine if a combined IV amino acid supplementation and in-bed cycle ergometry exercise intervention, compared to usual care, improves in hospital muscle strength and performance-based physical functioning outcomes in critically ill patients, using a primary endpoint of six-minute walk distance (6MWD) at hospital discharge.
Body composition. To determine if the combined intervention, compared to usual care, improves amino acid utilization and decreases muscle wasting in ICU patients (secondary endpoints).
Patient-reported outcomes and health care utilization at 6 months. To determine if the combined intervention, compared to usual care, improves physical functioning, health-related quality of life, and healthcare utilization at 6 months after study enrollment (secondary endpoints).

NEXIS Flame mechanisitic Ancillary sub study:

Specific Aims of the NEXIS FLAME mechanistic ancillary study:

To determine if the NEXIS intervention attenuates the release of IL-17 and related cytokines to reduce systemic inflammation in humans.
To determine if the NEXIS intervention reduces lung injury and neutrophilic lung inflammation in humans.
To determine if the NEXIS intervention attenuates skeletal muscle fiber atrophy via down regulation of muscle proteolytic pathways.
To determine if the NEXIS intervention, and exercise specifically, reduces the content of inflammatory cells in skeletal muscle.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (outcomes assessor)
Number of arms: 2

Arm	Type	Receives
IV amino acid + in-bed cycle ergometry	Experimental	Drug: IV amino acids, Device: In-bed cycle ergometry exerciseBeginning within 96 hours of initiation of mechanical ventilation, participants will receive the combined intervention that includes IV amino acids supplementation and in-bed cycle ergometry exercise
Usual care	No intervention	–Participants randomized to the usual care arm will receive usual care protein and exercise.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

≥18 years old.
Requiring mechanical ventilation with actual or expected total duration of mechanical ventilation ≥ 48 hours.
Expected ICU stay ≥ 4 days after enrollment (to permit adequate exposure to the proposed intervention).

Key exclusion criteria (23 listed)

>96 continuous hours of mechanical ventilation before enrollment.
Expected death or withdrawal of life-sustaining treatments within this hospitalization.
No expectation for any nutritional intake within the subsequent 72 hours.
Severe chronic liver disease (MELD score ≥20) or acute fulminant hepatitis.
Documented allergy to the amino acid intervention.

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
IV amino acidsAlso: Clinisol 15% (Baxter) - sulfite-free (Amino Acid) InjectionIV amino acids delivered by continuous infusion, such that the total enteral and IV protein will be between 2.0-2.5 g/kg/day as a combination of amino acid infusion plus standard feeding.	Drug	IV amino acid + in-bed cycle ergometry
In-bed cycle ergometry exerciseAlso: MotoMed Letto II Cycle ErgometerIn-bed cycle ergometry exercise delivered in 45-minute sessions once-daily 5 days per week according to a detailed specific protocol that includes a safety check in combination with vigorous verbal encouragement from trained research staff delivering the intervention to promote active cycling. Cycling is protocolized to provide graduated increases in resistance during each session and between daily sessions. Cycling will continue through ICU discharge or 21 calendar days after randomization. The intervention will specifically occur during ICU stay.	Device	IV amino acid + in-bed cycle ergometry

Primary outcome

Physical functioning
Time frame: Hospital discharge (up to 26 weeks after randomization)
6-minute walk distance

34 secondary outcomes

Overall strength-upper extremity
Time frame: Hospital discharge (up to 26 weeks after randomization)
Overall strength-lower extremity
Time frame: Hospital discharge (up to 26 weeks after randomization)
Quadriceps force-lower extremity strength
Time frame: Hospital discharge (up to 26 weeks after randomization)
Distal strength-hand grip strength
Time frame: ICU and hospital discharge (up to 26 weeks after randomization)
Overall Physical Functional status - Short Physical Performance Battery
Time frame: ICU and hospital discharge (up to 26 weeks after randomization)
Overall Physical Functional status - Functional Status Score - ICU
Time frame: ICU and hospital discharge (up to 26 weeks after randomization)
Mortality
Time frame: ICU and hospital discharge (up to 26 weeks after randomization)
Length of ventilation
Time frame: ICU and hospital discharge (up to 26 weeks after randomization)
ICU stay
Time frame: ICU and hospital discharge (up to 26 weeks after randomization)
Hospital stay
Time frame: ICU and hospital discharge (up to 26 weeks after randomization)
ICU readmission
Time frame: Hospital discharge (up to 26 weeks after randomization)
Re-intubation
Time frame: Hospital discharge (up to 26 weeks after randomization)
Hospital-acquired infections
Time frame: Hospital discharge (up to 26 weeks after randomization)
Discharge location (e.g. home vs. rehab)
Time frame: Hospital discharge (up to 26 weeks after randomization)
Body composition - Ultrasound
Time frame: Enrollment, hospital discharge, & ICU discharge (up to 26 weeks after randomization)
Body composition - CT - Chest when clinically available
Time frame: Enrollment, hospital discharge, & ICU discharge (up to 26 weeks after randomization)
Body composition - CT - Abdominal Scan when clinically available
Time frame: Enrollment, hospital discharge, & ICU discharge (up to 26 weeks after randomization)
Health-related quality of life - SF-36
Time frame: Telephone survey at 6 months
Health-related quality of life - EQ-5D-5L
Time frame: Telephone survey at 6 months
Physical functioning - Katz ADL
Time frame: Hospital discharge (proxy) and telephone survey at 6 months
Physical functioning - Lawton IADL
Time frame: Telephone survey at 6 months
Physical functioning/participation - return to work
Time frame: Telephone survey at 6 months
Physical functioning/participation - living location
Time frame: Telephone survey at 6 months
Mental and Cognitive Functioning - MoCA-BLIND
Time frame: Telephone survey at 6 months
Mental and Cognitive Functioning - HADS
Time frame: Telephone survey at 6 months
Mental and Cognitive Functioning - IES-R
Time frame: Telephone survey at 6 months
Health Care Resource Utilization
Time frame: Telephone survey at 6 months
Body composition - DEXA Scan
Time frame: At Hospital Discharge
Body Composition - Heavy water
Time frame: Enrollment, Days 1-7
Plasma and muscle protein synthesis - Heavy water
Time frame: Enrollment, Days 1-7
NEXIS FLAME - Circulating inflammatory mediators
Time frame: Enrollment, Days 3, 5, and 8
NEXIS FLAME - Lung Inflammation
Time frame: Enrollment, Day 5
NEXIS FLAME - Muscle area
Time frame: Enrollment, Day 5
NEXIS FLAME - Muscle inflammation
Time frame: Enrollment, Day 5

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 27 Aug 2025.
Background: PubMed 19623052Burtin C, Clerckx B, Robbeets C, Ferdinande P, Langer D, Troosters T, Hermans G, Decramer M, Gosselink R. Early exercise in critically ill patients enhances short-term functional recovery. Crit Care Med. 2009 Sep;37(9):2499-505. doi: 10.1097/CCM.0b013e3181a38937.
Background: PubMed 25742048Chan KS, Pfoh ER, Denehy L, Elliott D, Holland AE, Dinglas VD, Needham DM. Construct validity and minimal important difference of 6-minute walk distance in survivors of acute respiratory failure. Chest. 2015 May;147(5):1316-1326. doi: 10.1378/chest.14-1808.
Background: PubMed 25307979Kho ME, Truong AD, Zanni JM, Ciesla ND, Brower RG, Palmer JB, Needham DM. Neuromuscular electrical stimulation in mechanically ventilated patients: a randomized, sham-controlled pilot trial with blinded outcome assessment. J Crit Care. 2015 Feb;30(1):32-9. doi: 10.1016/j.jcrc.2014.09.014. Epub 2014 Sep 22.
Background: PubMed 23594003Heyland D, Muscedere J, Wischmeyer PE, Cook D, Jones G, Albert M, Elke G, Berger MM, Day AG; Canadian Critical Care Trials Group. A randomized trial of glutamine and antioxidants in critically ill patients. N Engl J Med. 2013 Apr 18;368(16):1489-97. doi: 10.1056/NEJMoa1212722.
Background: PubMed 22307571National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network; Rice TW, Wheeler AP, Thompson BT, Steingrub J, Hite RD, Moss M, Morris A, Dong N, Rock P. Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. JAMA. 2012 Feb 22;307(8):795-803. doi: 10.1001/jama.2012.137. Epub 2012 Feb 5.
Background: PubMed 24835849National Heart, Lung, and Blood Institute ARDS Clinical Trials Network; Truwit JD, Bernard GR, Steingrub J, Matthay MA, Liu KD, Albertson TE, Brower RG, Shanholtz C, Rock P, Douglas IS, deBoisblanc BP, Hough CL, Hite RD, Thompson BT. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med. 2014 Jun 5;370(23):2191-200. doi: 10.1056/NEJMoa1401520. Epub 2014 May 18.
Background: PubMed 22983782Parry SM, Berney S, Koopman R, Bryant A, El-Ansary D, Puthucheary Z, Hart N, Warrillow S, Denehy L. Early rehabilitation in critical care (eRiCC): functional electrical stimulation with cycling protocol for a randomised controlled trial. BMJ Open. 2012 Sep 13;2(5):e001891. doi: 10.1136/bmjopen-2012-001891. Print 2012.
Background: PubMed 19638746Fan E, Zanni JM, Dennison CR, Lepre SJ, Needham DM. Critical illness neuromyopathy and muscle weakness in patients in the intensive care unit. AACN Adv Crit Care. 2009 Jul-Sep;20(3):243-53. doi: 10.1097/NCI.0b013e3181ac2551.
Background: PubMed 18766087Dowdy DW, Dinglas V, Mendez-Tellez PA, Bienvenu OJ, Sevransky J, Dennison CR, Shanholtz C, Needham DM. Intensive care unit hypoglycemia predicts depression during early recovery from acute lung injury. Crit Care Med. 2008 Oct;36(10):2726-33. doi: 10.1097/CCM.0b013e31818781f5.
Derived from this study: PubMed 42438140Needham DM, Files DC, Hough CL, Mayer KP, Ardren S, Fatima A, Jiang X, Day AG, Dinglas VD, Hiser SL, Kiyatkin ME, Khan A, Morris PE, Carson SS, Antkowiak M, Bakhru RN, Burns S, Nath SD, Gibbs KW, Gundel SJ, Kalema AG, Sturgill JL, Ventrone S, Heyland DK, Stapleton RD; With The NEXIS Study Team. Nutrition and Exercise in Critical Illness (NEXIS) trial: randomized trial of combined in-bed cycling and intravenous amino acid plus usual care. Am J Respir Crit Care Med. 2026 Jul 13:aamag287. doi: 10.1093/ajrccm/aamag287. Online ahead of print.
Derived from this study: PubMed 34930871Al-Dorzi HM, Stapleton RD, Arabi YM. Nutrition priorities in obese critically ill patients. Curr Opin Clin Nutr Metab Care. 2022 Mar 1;25(2):99-109. doi: 10.1097/MCO.0000000000000803.
Derived from this study: PubMed 31371287Heyland DK, Day A, Clarke GJ, Hough CT, Files DC, Mourtzakis M, Deutz N, Needham DM, Stapleton R. Nutrition and Exercise in Critical Illness Trial (NEXIS Trial): a protocol of a multicentred, randomised controlled trial of combined cycle ergometry and amino acid supplementation commenced early during critical illness. BMJ Open. 2019 Jul 31;9(7):e027893. doi: 10.1136/bmjopen-2018-027893.
Individual participant dataSharing planned: No. There is no plan to share IPD.

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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.

Daren K Heyland, MD, MSc principal investigator

Queen's University

Renee D Stapleton, MD, PhD principal investigator

University of Vermont

Dale M Needham, MD, PhD principal investigator

Johns Hopkins University

7 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 3 inclusion and 23 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 27 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States. 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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?

Physical functioning (time frame: Hospital discharge (up to 26 weeks after randomization)). 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 NCT03021902, which also lists 12 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 27 Aug 2025.