A Study Promoting Critical Illness Recovery in the Elderly

ASPIRE: A Study Promoting Critical Illness Recovery in the Elderly

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02963558

Acronym

ASPIRE

Enrollment

Registered

2016-11-15

Start date

2017-05-30

Completion date

2021-03-11

Last updated

2024-10-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute Respiratory Distress Syndrome, Critical Care, Critical Illness

Brief summary

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

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.

Interventions

DEVICEcycle ergometry

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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

55 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Number of Patients in the Intervention Arm Who Are Able to Undergo a Cycling Session	up to 48 hours after randomization	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.

Secondary

Measure	Time frame	Description
Handgrip Strength	ICU Discharge, Hospital discharge (through study completion, on average day 10)	Assessed with a Jamar hand-held dynamometer.
Mobility Assessment Tool-short Form (MAT-sf)	Day 0, ICU discharge, Hospital discharge	A scoring system from 30 to 80 with 80 meaning higher physcial function
Montreal Cognitive Assessment (MoCA)	hospital discharge, month 3, month 6	screening instrument for mild cognitive dysfunction; range 0-30; lower score means more cognitive impairment
Quad Strength	ICU Discharge, Hospital discharge	Measurement of quadriceps strength while sitting.
Short Form-36	hospital discharge	Assesses quality of life. Score for each part of the questionnaire ranges from 0 to 100. Data will be collected for the following parts: Physical functioning, Role Limited Due to Physical Health, Role Limited Due to Emotional Problems, Energy/Fatigue, Emotional Well-being, Social Functioning, Pain, General Health. For each of these a higher score means better function/less impariment in regards to each item.
Muscle Ultrasound--tibialis Anterior Depth	day 0, day 3, day 5, ICU discharge, Hospital Discharge	The study team is measuring the percentage of the size of the cross-sectional area of the tibialis anterior. Day 0 for everyone is 100% (starting point). The study team is measuring the percentage of that starting point at other time points.
Muscle Ultrasound--echogenicity in the Tibialis Anterior	day 0, day 3, day 5, ICU discharge, Hospital Discharge	Obtain preliminary data to estimate the treatment effect size. Echogenicity is a measure called the grey scale measure. Scores range from 0-255. A higher score is brighter/more white on ultrasound. A lower score is darker. Think of this as exposure on a black and white picture.
Muscle Ultrasound--muscle Size CSA of Rectus Femoris Muscle	day 0, day 3, day 5, ICU discharge, Hospital Discharge	The study team is measuring the percentage of the size of the cross-sectional area of the rectus femoris. Day 0 for everyone is 100% (starting point). The study team is measuring the percentage of that starting point at other time points.
Muscle Ultrasound--echogenicity in the Rectus Femoris Muscle	day 0, day 3, day 5, ICU discharge, Hospital Discharge	Obtain preliminary data to estimate the treatment effect size. Echogenicity is a measure called the grey scale measure. Scores range from 0-255. A higher score is brighter/more white on ultrasound. A lower score is darker. Think of this as exposure on a black and white picture.
Muscle Ultrasound--muscle Depth Quadriceps	day 0, day 3, day 5, ICU discharge, Hospital Discharge	The study team is measuring the percentage of the size of the cross-sectional area of the quadriceps. Day 0 for everyone is 100% (starting point). The study team is measuring the percentage of that starting point at other time points.
Short Physical Performance Battery (SPPB)	Intensive Care Unit (ICU) discharge (through study completion, on average day 10)	Based on timed measures of standing balance, walking speed, and ability to rise from a chair. Scores range from 0-12. A higher score denotes a better outcome.

Other

Measure	Time frame	Description
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	—
Translational Outcomes	up to 6 months	MuRF1, NFKB, myofiber size and type, etc
Hospital Length of Stay	Hospital discharge (through study completion, on average day 10)	Number of days
Mortality	up through 6 months post-discharge	total number affected
Intensive Care Unit (ICU) Length of Stay	ICU discharge (through study completion, on average day 7)	Number of days
Accelerometer Activity Monitoring Results	Up through two weeks after discharge	Used to determine activity.
Number of Hospital Readmissions	up to 6 months	—

Countries

United States

Participant flow

Participants by arm

Arm	Count
Intervention 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. cycle ergometry: 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.	13
Usual Care 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.	9
Total	22

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Withdrawal by Subject	0	1
Overall Study	Withdrawn by investigator	1	0

Baseline characteristics

Characteristic	Intervention	Total	Usual Care
Age, Continuous	64 years	68 years	71 years
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	3 Participants	4 Participants	1 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	10 Participants	18 Participants	8 Participants
Region of Enrollment United States	13 participants	22 participants	9 participants
Sex: Female, Male Female	5 Participants	9 Participants	4 Participants
Sex: Female, Male Male	8 Participants	13 Participants	5 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	4 / 13	2 / 9
other Total, other adverse events	0 / 13	0 / 9
serious Total, serious adverse events	4 / 13	2 / 9

Outcome results

Primary

Number of Patients in the Intervention Arm Who 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.

Time frame: up to 48 hours after randomization

Population: This outcome only pertains to the interventional arm.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Intervention	Number of Patients in the Intervention Arm Who Are Able to Undergo a Cycling Session	13 Participants
Usual Care	Number of Patients in the Intervention Arm Who Are Able to Undergo a Cycling Session	0 Participants

Secondary

Handgrip Strength

Assessed with a Jamar hand-held dynamometer.

Time frame: ICU Discharge, Hospital discharge (through study completion, on average day 10)

Arm	Measure	Group	Value (MEDIAN)
Intervention	Handgrip Strength	ICU Discharge	11.33 kilograms
Intervention	Handgrip Strength	Hospital Discharge	14.33 kilograms
Usual Care	Handgrip Strength	ICU Discharge	11.33 kilograms
Usual Care	Handgrip Strength	Hospital Discharge	8.67 kilograms

Secondary

Mobility Assessment Tool-short Form (MAT-sf)

A scoring system from 30 to 80 with 80 meaning higher physcial function

Time frame: Day 0, ICU discharge, Hospital discharge

Arm	Measure	Group	Value (MEDIAN)
Intervention	Mobility Assessment Tool-short Form (MAT-sf)	Day 0	55.4 score on a scale
Intervention	Mobility Assessment Tool-short Form (MAT-sf)	ICU Discharge	42.8 score on a scale
Intervention	Mobility Assessment Tool-short Form (MAT-sf)	Hospital Discharge	45.4 score on a scale
Usual Care	Mobility Assessment Tool-short Form (MAT-sf)	Day 0	49.12 score on a scale
Usual Care	Mobility Assessment Tool-short Form (MAT-sf)	ICU Discharge	54.0 score on a scale
Usual Care	Mobility Assessment Tool-short Form (MAT-sf)	Hospital Discharge	47 score on a scale

Secondary

Montreal Cognitive Assessment (MoCA)

screening instrument for mild cognitive dysfunction; range 0-30; lower score means more cognitive impairment

Time frame: hospital discharge, month 3, month 6

Population: Not adminstered at month 3 and month 6; no data collected for those time frames

Arm	Measure	Group	Value (MEDIAN)
Intervention	Montreal Cognitive Assessment (MoCA)	Hospital discharge	18.5 score on a scale
Usual Care	Montreal Cognitive Assessment (MoCA)	Hospital discharge	19 score on a scale

Secondary

Muscle Ultrasound--echogenicity in the Rectus Femoris Muscle

Obtain preliminary data to estimate the treatment effect size. Echogenicity is a measure called the grey scale measure. Scores range from 0-255. A higher score is brighter/more white on ultrasound. A lower score is darker. Think of this as exposure on a black and white picture.