Time Window for Ischemic Stroke First Mobilization Effectiveness (TIME)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Brain Ischemia; Stroke Rehabilitation
• Intervention / Treatment: Other: early rehabilitation

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 1500
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lu Xiao, MD/PHD; Phone Number: 3029 +86 025-83718836; Email: luxiao1972@163.com
• Study Contact Backup: Name: Yan Chengjie, postgraduate; Phone Number: +8615995610375; Email: jiabailie00@sina.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Recruiting
      • The First Affiliated Hospital of Nanjing Medical University (Jiangsu Provincial People's Hospital)
      • Contact: Yan Chengjie, postgraduate; Phone Number: +8615995610375; Email: jiabailie00@sina.com
      • Contact: Zhang Xintong, Xintong; Phone Number: +8615720802936
      • Sub-Investigator: Yan Chengjie, postgraduate

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: very early rehabilitation; early mobilization initiates within 24h from the onset of the disease	Other: early rehabilitation; 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.
Experimental: relative early rehabilitation; early mobilization initiates between 24-72h from the onset of the disease	Other: early rehabilitation; 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.
Experimental: late mobilization group; early mobilization initiates after 72h from the onset of the disease	Other: early rehabilitation; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
CBF	cerebral blood flow	the count of CBF will be recorded 3months after the cerebrovascular accident/or the last time appeared normally
CBV	cerebral blood volume	the count of CBV will be recorded 3months after the cerebrovascular accident/or the last time appeared normally
FA	fractional anisotropy, a outcome of diffusion tensor imaging	3months after the cerebrovascular accident/or the last time appeared normally
MD	mean diffusivity,a outcome of diffusion tensor imaging	3months after the cerebrovascular accident/or the last time appeared normally
rsFC	resting-state functional connectivity	the rsFC description will be recorded by a radiologist 3months after the cerebrovascular accident/or the last time appeared normally

Collaborators and Investigators

• Sponsor: China Stroke Databank Center
• Collaborators: The First Affiliated Hospital with Nanjing Medical University; Wuhan University; First Affiliated Hospital of Fujian Medical University; Shandong Provincial Hospital; The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Zhengzhou University; Tianjin Medical University General Hospital; Hainan General Hospital; The First Affiliated Hospital of Shanxi Medical University; First Affiliated Hospital of Xinjiang Medical University; The First Hospital of Hebei Medical University; Xingtai People's Hospital; Cangzhou Central Hospital; First Affiliated Hospital Bengbu Medical College; The Affiliated Hospital of Xuzhou Medical University; Anhui Provincial Hospital; The First People's Hospital of Lianyungang; Zibo Central Hospital; Shanghai Pudong Hospital; Liaocheng People's Hospital; First People's Hospital of Yulin; Jingmen No.1 People's Hospital; Chongqing Three Gorges Central Hospital; Nanjing Jiangbei People's Hospital; Nanjing Tongren Hospital
• Investigators: Principal Investigator: Lu Xiao, MD/PHD, The First Affiliated Hospital with Nanjing Medical University

Publications and helpful links

General Publications

• Zheng Y, Yan C, Shi H, Niu Q, Liu Q, Lu S, Zhang X, Cheng Y, Teng M, Wang L, Zhang X, Hu X, Li J, Lu X, Reinhardt JD; TIME Trial Collaboration Group. Time Window for Ischemic Stroke First Mobilization Effectiveness: Protocol for an Investigator-Initiated Prospective Multicenter Randomized 3-Arm Clinical Trial. Phys Ther. 2021 May 4;101(5):pzab038. doi: 10.1093/ptj/pzab038.

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2019
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: April 27, 2019
• First Submitted That Met QC Criteria: May 2, 2019
• First Posted (Actual): May 6, 2019

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 26, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Acute ischemic stroke; early mobilization; early rehabilitation; time window; multicenter randomized controlled trial
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Brain Ischemia; Ischemia
• Other Study ID Numbers: GN-2018R0010

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No