Time Window for Ischemic Stroke First Mobilization Effectiveness

Study Overview
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Brief Summary
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Early mobilization was thought to be effective in patients with acute ischemic stroke. As the essential component of stroke unit care, early mobilization has already been part of routine clinical practice. However, it is uncertain that which and when medical service focusing on functional recovery should be delivered after the emergency interventions for stroke. Besides, the optimal time window, for delivering early mobilization after acute ischemic stroke, has not been verified with strong evidence.

Detailed Description
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The TIME Trial is a pragmatic, investigator-initiated, multi-center, randomized, 3-arm parallel group, clinical trial. This trial will be conducted in 57 general hospitals in mainland China affiliated with the China Stroke Databank Center and will enroll 6033 eligible patients with acute ischemic stroke. Participants will be randomly allocated to either (1) the very early mobilization group in whichmobilization is initiated within 24 hours from stroke onset, (2) the early mobilization group in which mobilization begins between 24 and 72 hours poststroke, or (3) the late mobilization group in which mobilization is started after 72 hours poststroke. The mobilization protocol is otherwise standardized and identical for each comparison group. Mobilization is titrated by baseline mobility level and progress of patients throughout the intervention period. The primary outcome is death or disability assessed with the modified Rankin scale at 3 months poststroke. Secondary outcomes include impairment score of the National Institutes of Health Stroke Scale, dependence in activities of daily living as measured using the modified Barthel Index, cognitive ability assessed with the Mini-Mental State Examination, incidence of adverse events, hospital length of stay, and total medical costs. Study design: an Investigator-Initiated Prospective Multicenter Randomized 3-Arm Clinical Trial Sample size: 1500 cases

Official Title
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Time Window for Early Mobilization in Improving Prognostic Outcomes in Patients With Acute Ischemic Stroke: an Investigator-Initiated Prospective Multicenter Randomized 3-Arm Clinical Trial

Conditions
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Brain Ischemia, Stroke Rehabilitation

Intervention / Treatment
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* Other: early rehabilitation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1 diagnosed with ischemic stroke through anamnesis, clinical symptoms, and radiographic assessment; 2 aged 18 years or older; 3 of ischemic stroke within 12 hours before eligibility check; 4 able to verbally respond to the instructions; 5 with stable vital signs (systolic blood pressure 120-180 mmHg, heart rate 50-100/min, body temperature <37.5◦C, blood oxygen saturation >92%) 6MMSE score > 16; 7participation in the TIME Trial and sign the consent form. Exclusion Criteria: 1 diagnosed with hemorrhagic stroke; 2 NIHSS score < 2; 3 pre-morbid modified Ranking Scale (mRS) score of 3-5; 4 refusing randomization; 5 having severe limb dysfunction or systemic diseases rendering them unable to cooperate in the mobilization intervention; 6 having severe cognitive and mental dysfunctions; 7 currently enrolled in another trial or having participated in a clinical trial within 6 months before stroke onset.

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: Patients with acute ischemic stroke fulfilling the inclusion and exclusion criteria will be randomly allocated to either either (1) the very early mobilization group in whichmobilization is initiated within 24 hours from stroke onset, (2) the early mobilization group in which mobilization begins between 24 and 72 hours poststroke, or (3) the late mobilization group in which mobilization is started after 72 hours poststroke.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: very early rehabilitation<br>early mobilization initiates within 24h from the onset of the disease | Other: early rehabilitation<br>* The three study groups share a same intervention protocol in addition to the initiation timing of intervention from the stroke onset. The frequency and intensity of the intervention is titrated according to functional activity baseline and monitored daily and adjusted with recovery. Encourage patients to move out of bed as soon as possible. Definition of bed movement: Encourage and help patients to perform functional actions, focusing on activities such as sitting, standing, walking out of the bed.<br>|
| Experimental: relative early rehabilitation<br>early mobilization initiates between 24-72h from the onset of the disease | Other: early rehabilitation<br>* The three study groups share a same intervention protocol in addition to the initiation timing of intervention from the stroke onset. The frequency and intensity of the intervention is titrated according to functional activity baseline and monitored daily and adjusted with recovery. Encourage patients to move out of bed as soon as possible. Definition of bed movement: Encourage and help patients to perform functional actions, focusing on activities such as sitting, standing, walking out of the bed.<br>|
| Experimental: late mobilization group<br>early mobilization initiates after 72h from the onset of the disease | Other: early rehabilitation<br>* The three study groups share a same intervention protocol in addition to the initiation timing of intervention from the stroke onset. The frequency and intensity of the intervention is titrated according to functional activity baseline and monitored daily and adjusted with recovery. Encourage patients to move out of bed as soon as possible. Definition of bed movement: Encourage and help patients to perform functional actions, focusing on activities such as sitting, standing, walking out of the bed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| modified Rankin Scale | modified Rankin Scale, to evaluate a subject's disability status. It's a rating data. The degrees range from 0 to 6, higher values represent a worse outcome and severe disability. | 3 months after the cerebrovascular accident/or the last time appeared normally | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Barthel Index | ability of daily living, total scores range from 0 to 100, higher values represent a better outcome and independent living ability. | the total score of Barthel Index will be recorded 15days、1month、3 months、6months after the cerebrovascular accident/or the last time appeared normally | 
| modified Rankin Scale | modified Rankin Scale, to evaluate a subject's disability status. It's a rating data. The degrees range from 0 to 6, higher values represent a worse outcome and severe disability. | the total score of mRS will be recorded 15days、1month、6months after the cerebrovascular accident/or the last time appeared normally | 
| MMSE | Mini-mental State Examination. To evaluate a subject's mental state.The total score range from 0 to 30, higher values represent a better outcome. | the total score of MMSE will be recorded 15days、1month、3 months、6months after the cerebrovascular accident/or the last time appeared normally | 
| NIHSS scores | National Institute of Health stroke scale，total scores range from 0 to 42, higher values represent a better outcome. | the total score of NIHSS will be recorded15days、1month、6months after the cerebrovascular accident/or the last time appeared normally | 
| Incidence of important medical events | falls, trauma, fracture, syncope, epilepsy, pneumonia, atelectasis, venous thrombosis, pulmonary embolism, pressure sores, death, etc. | The incidence of important medical events will be recorded 15days、1month、3 months after the cerebrovascular accident/or the last time appeared normally | 
| Hospital LOS | length of stay in the acute hospital and in the rehabilitation hospital, and total hospital length of stay | Hospital LOS will be recorded 3 months after the cerebrovascular accident/or the last time appeared normally | 
| Total medical cost | addition of the cost of each admission of the acute hospital and the rehabilitation hospital | medical cost will be recorded 3 months after the cerebrovascular accident/or the last time appeared normally | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute ischemic stroke, early rehabilitation, early mobilization, time window, multicenter randomized controlled trial