A Study Promoting Critical Illness Recovery in the Elderly

Study Overview
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Brief Summary
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This proposal will test the hypothesis that EARLY application of a novel early rehabilitation therapy in critically ill patients will improve functional outcomes, and change the functional trajectory of this population. A pilot study of early mobilization with a cycle ergometer will be performed and translate into humans the pre-clinical mechanisms that may mediate the effects of early mobility. A second phase of the study was added in September 2019, which will focus on clinical outcomes.

Detailed Description
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Patients will be randomized to intervention or control groups. Patients will receive therapies according to their group assignment until hospital discharge or day 28, whichever comes first. The intervention group will receive in-bed cycle ergometry within 48 hours of randomization if safety criteria are met. In-bed cycle ergometry has been shown to be safe and feasible in the critically ill and is approved for use in this population. Subjects enrolled in the intervention arm will be screened at least 5 days per week to evaluate if they meet pre-defined safety criteria based on other studies of early mobilization and cycling in the Intensive Care Unit (ICU). Patients will be positioned in the semi-recumbent position for cycling as per ICU guidelines. The cycler will provide 3 different possible modes of cycling-passive, active-assisted, and active. The investigators will start with passive cycling and the patient may progress to active-assisted and active cycling. The goal duration of cycling will be 30 minutes. Subjects will receive in-bed cycling at least 5 times per week for the duration of the ICU stay or until day 14, whichever comes first. During cycling and therapy sessions, the physical therapist will also complete a case report form noting vital signs, level of mobilization, and other safety measures. In addition to cycling, the intervention arm will receive early physical therapy (PT). This physical therapy will be performed according to a protocol of additional ICU and hospital-administered rehabilitation strategies that were previously developed. Patients will receive 30 minutes of Physical Therapy (PT) at least 5 times per week when they are conscious. If unconscious, subjects will only receive passive range of motion (PROM) for 10 repetitions per body part daily. Once conscious, subjects will progress through the different levels of PT with an emphasis on ambulation. Physical therapy for the intervention arm patients will continue while hospitalized through day 28. Outpatient therapy will be provided at the discretion of the patient's treating physicians. The control group will receive usual care physical therapy as ordered by the treating team both in the ICU and on the floor through hospital discharge. These subjects will also receive therapy as outpatients only as ordered by their physicians.

Official Title
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ASPIRE: A Study Promoting Critical Illness Recovery in the Elderly

Conditions
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Acute Respiratory Distress Syndrome, Critical Illness, Critical Care

Intervention / Treatment
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* Device: cycle ergometry


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥55 years old Admission to Wake Forest Baptist Medical Center Medical Intensive Care Unit Acute Hypoxic respiratory failure on mechanical ventilation for <48 hours with a P:F ratio of <300 (or equivalent S:F ratio) Previously Functional (over past 3 months, as reported by proxy): Physical Function: Able to walk 4 m (with or without assistive device) Exclusion Criteria: Neuromuscular Disease Cardiopulmonary Arrest with return of spontaneous circulation <6 hrs Palliative Goals of Care; witholding life-sustaining therapy Elevated Intracranial Pressure (>20 mm Hg) BMI>45; absolute weight >= 150 kg Inability to cycle (including absent limbs, body length <1.5m, body habitus not fitting the cycle, inflammatory arthritis, significant joint problems including inability to bend arms/legs; pelvic and/or LE fracture, LE bypass surgery) Pregnancy Unable to speak English Use of continuous neuromuscular blockade Temporary Pacemaker or Swan Ganz catheter or femoral ECMO catheter/IABP Rhabdomyolysis with most recent CK >5000 Clinical diagnosis of dementia on medication Moribund Possible Exclusion: If the patient is on spine precautions, a discussion with the spine team will be necessary to determine eligibility for the study

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>The intervention group will receive in-bed cycle ergometry within 48 hours of randomization if safety criteria are met. The intervention arm will receive early physical therapy (PT). This PT will be performed according to a protocol of additional ICU and hospital-administered rehabilitation strategies that have been previously developed. Patients will receive 30 minutes of PT at least 5 times per week while conscious. If unconscious, subjects will only receive passive range of motion (PROM) for 10 repetitions per body part daily. Once conscious, subjects will progress through PT with an emphasis on ambulation. Therapy for the intervention arm patients will continue while on the floor. Outpatient therapy will be provided at the discretion of the patient's treating physicians. | Device: cycle ergometry<br>* The cycler will provide 3 different possible modes of cycling-passive, active-assisted, and active. The subject will start with passive cycling and may progress to active-assisted and active cycling.<br>* Other names: MOTOmed;|
| No Intervention: Usual Care<br>The control group will receive usual care physical therapy as ordered by the treating team both in the ICU and on the floor through hospital discharge. These subjects will also receive therapy as outpatients only as ordered by their regular physicians. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients in the intervention arm the are able to undergo a cycling session | Feasibility will be assessed by quantifying the ability to apply the MOTOmed device for at least a 15-minute session within 48 hours of randomization and meeting safety criteria. | up to 48 hours after randomization | 
| Short Physical Performance Battery (SPPB) | Based on timed measures of standing balance, walking speed, and ability to rise from a chair. Each measure is assigned a score ranging from 0 to 4, with a total possible summary score of 12. A higher score denotes a better outcome. | Intensive Care Unit (ICU) discharge (through study completion, on average day 7) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short Physical Performance Battery (SPPB) | Based on timed measures of standing balance, walking speed, and ability to rise from a chair. Each measure is assigned a score ranging from 0 to 4, with a total possible summary score of 12. A higher score denotes a better outcome. | Hospital discharge (through study completion, on average day 10) | 
| Handgrip strength | Assessed with a Jamar hand-held dynamometer. | Hospital discharge (through study completion, on average day 10) | 
| Intensive Care Unit (ICU) Length of Stay | Number of days | ICU discharge (through study completion, on average day 7) | 
| Hospital Length of Stay | Number of days | Hospital discharge (through study completion, on average day 10) | 
| Number of Hospital Readmissions |  | up to 6 months | 
| Number of Emergency Department Visits |  | up to 6 months | 
| Number of Ventilator Free Days |  | Up to 28 days from hospital admission or hospital discharge, whichever is first | 
| Mortality | total number affected | up through 6 months post-discharge | 
| Short Form-36 | Assesses quality of life. Score ranges from 0 to 100 with a higher score denoting a higher outcome. | through study completion (hospital discharge, 3 months post-discharge, 6 months post-discharge) | 
| Accelerometer Activity Monitoring Results | Used to determine activity. | Up through two weeks after discharge | 
| Muscle Ultrasound--thickness, size, echogenicity; DXA scans | Obtain preliminary data to estimate the treatment effect size | up to 6 months | 
| Translational Outcomes | MuRF1, NFKB, myofiber size and type, etc | up to 6 months |