r-tPA Thrombolytic Therapy in Combination With Remote Ischemic Conditioning for Acute Ischemic Stroke Recovery (rtPA-RIC)

Intravenous Rt-PA Thrombolysis Combined With Remote Ischemic Post-Conditioning for Acute Ischemic Stroke Patients

to detect the efficiency and safety of intravenous rtPA combined with RIPC in acute ischemic stroke patients

Study Overview

• Status: Unknown
• Conditions: Stroke, Acute
• Intervention / Treatment: Device: ischemic conditioning

Detailed Description

Remote ischemic post-conditioning, which consists of several brief cycles of intermittent ischemia-reperfusion of the arm or leg, may potentially confer a powerful systemic protection against prolonged ischemia in a distant organ. Numerous reports have confirmed it strongest endogenous neuroprotection against brain injury after stroke. Ren et al demonstrated that remote ischemic post-conditioning (RIPC) performed in the hind limbs can not only significantly reduce the stroke volume within 3 hours in rat model, but also ameliorate the outcome of the behavioral test. A long-term repeated RIPC therapy can also help improving neurological functions. A combination of RIPC and tPA can help with neuroprotection which improves the neurological functions. Thus, it is meaningful to transform these basic experimental results to the clinical treatment. In the RECAST-1 trial, RIC has shown it safety and efficiency in AIS patients without tPA. However, there is no further explanation for the patients with IVT. Thus, in this study, we aim to demonstrate the efficiency and safety of RIPC in AIS patients performed rt-PA within 4.5 hours.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100053
      • Recruiting
      • Xuanwu Hospital, Capital Medical University
      • Contact: Ruiwen Che, MD; Email: rwcadl@163.com
    • Beijing, Beijing, China, 101149
      • Not yet recruiting
      • Lu He hospital, Capital Medical University
      • Contact: Geng, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female, age≥18;
• Clinical sign and symptoms consistent with the diagnosis of an acute ischemic stroke, onset of stroke symptoms within 4.5 h before initiation of intravenous rt-PA thrombolytic therapy;
• Baseline National Institutes of Health Stroke Scale (NIHSS) score of 4-15 (assessed before intravenous alteplase), mRS ≤1 before onset of stroke symptom;
• No contraindication for MRI.
• Informed consent obtained

Exclusion Criteria:

• Cardioembolism；
• Contraindication for remote ischemic conditioning: severe soft tissue injury, fracture, or peripheral vascular disease in the upper limbs;
• Life expectancy < 1 year;
• Pregnant or breast-feeding women;
• Unwilling to be followed up or poor compliance for treatment; (5) Patients being enrolled or having been enrolled in other clinical trial within 3 months prior to this clinical trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RIC group; The upper limb ischemic conditioning is composed of five cycles of bilateral upper limb ischemia intervened by reperfusion, which is induced by two cuff placed around the upper arms respectively and inflated to 200 mm Hg for 5 minutes followed by 5 minutes of reperfusion by cuff deflation. This therapy started within 2 hours after r-tPA thrombolytic therapy. In addition, all participants receive a standard clinical therapy.	Device: ischemic conditioning; In this study, the remote ischemic conditioning treatment was composed of five cycles of bilateral upper limb ischemia intervened by reperfusion, which was induced by two cuff placed around the upper arms respectively and inflated to 200 mm Hg for 5 minutes followed by 5 minutes of reperfusion by cuff deflation.; Other Names: Doctormate, IPC-906
No Intervention: Control group; The participants received r-tPA thrombolytic therapy after diagnosed ischemic stroke. In addition, all participants receive a standard clinical therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
infarction volume in brain between two groups	assess by MRI-DWI and ADC	measured during 72 h

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The score of Modified Rankin scale score	The Modified Rankin Scale Score (mRS) is the most comprehensive and most widely used primary outcome measurement to assess the neurological functional disability in contemporary acute stroke trials. The mRS is an ordinal, graded interval scale that assigns patients among 7 global disability levels, which ranges from 0 (no symptom) to 5 (severe disability) and 6 (death). We will use mRS to evaluate the degree of disability or dependence during daily activities. The mRS will be assessed by certified study investigator, who is blinded to the treatment assignment, at 90 days postoperation. The distribution of mRS will be compared between groups	measured at baseline(before RIPC),24 hours, at 5-7 days,30±7 days, 90±7 days
proportional of Modified Rankin scale scored 0-1	The Modified Rankin Scale Score (mRS) is the most comprehensive and most widely used primary outcome measurement to assess the neurological functional disability in contemporary acute stroke trials. The mRS is an ordinal, graded interval scale that assigns patients among 7 global disability levels, which ranges from 0 (no symptom) to 5 (severe disability) and 6 (death). We will use mRS to evaluate the degree of disability or dependence during daily activities. The mRS will be assessed by certified study investigator, who is blinded to the treatment assignment, at 90 days postoperation. The distribution of mRS will be compared between groups	measured at baseline(before RIPC),24 hours, at 5-7 days,30±7 days, 90±7 days
The score of National Institute of Health stroke scale score	National Institute of Health Stroke Scale (NIHSS) is considered as a standardized assessment of neurological functions in the acute phase of stroke, and it is generally used to quantify patient's neurological impairments on 15 items in 11 fields of different neurological status.The score of the scale ranges from 0 to 42.And higher score indicates worse neurological function.	measured at baseline(before RIPC),24 hours, at 5-7 days,30±7 days, 90±7 days
The score of Barthel Index(BI)	the BI is used to measure performance in activities of daily living.The score of the scale ranges from 0 to 100. And lower score indicates worse activities of daily living.	measured at baseline(before RIPC),24 hours, at 5-7 days,30±7 days, 90±7 days
recurrence of stroke and TIA	Stroke recurrence was defined as sudden functional deterioration in neurologic status with a decrease of 4 or more in the NIHSS, or a new stroke lesion on MRI/DWI located at the territory of the affected intracranial arteries.	changes from baseline(before RIPC) to 90±7 days
death and any other adverse events	The investigator will record the number.	changes from baseline(before RIPC) to 90±7 days
any ICH	Head computed tomography or magnetic reasoning imaging (MRI) scan will be performed to confirm intracerebral hemorrhage, and the imaging will be evaluated by two independent neuroradiologists who are blinded to the study assignment.	changes from baseline(before RIPC) to 90±7 days
Distal radial pulses	professional doctors will check the distal radial pulses	during 90 days
Visual inspection for local edema	Professional oculists will check the fundus oculi to evaluate whether there is local edema.	during 90 days
The number of patients with erythema,and/or skin lesions related to RIC	Professional doctors will check it and the investigator will record the number.	during 90 days
Palpation for tenderness	Professional doctors will check it.	during 90 days
The number of patients not tolerating RIC procedure,and refuse to continue the RIC procedure	The investigator will record the number.	during 90 days
the score of Numeric Rating Scale (NRS)	The Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain. The score from 0-10. the higher	during 90 days
the score of Hamilton Rating Scale for Depression（HAMAD）	this score was used to provide an indication of depression, and as a guide to evaluate recovery.	change from baseline(before rtPA) to 90 days
level of MMP-9	Blood samples will be drawn from cubital vein to test these biomarkers.These samples will be centrifuged immediately after collection and stored at - 80 until batch evaluation	measured at baseline(before RIPC,after rtPA) and 7 days
level of IL-6	Blood samples will be drawn from cubital vein to test these biomarkers.These samples will be centrifuged immediately after collection and stored at - 80 until batch evaluation	measured at baseline(before RIPC,after rtPA) and 7 days
level of HS-CRP	Blood samples will be drawn from cubital vein to test these biomarkers.These samples will be centrifuged immediately after collection and stored at - 80 until batch evaluation	measured at baseline(before RIPC,after rtPA) and 7 days
The level of vascular endothelial growth factor	Blood samples will be drawn from cubital vein to test these biomarkersThese samples will be centrifuged immediately after collection and stored at - 80 until batch evaluation	measured at baseline(before RIPC,after rtPA) and 7 days

Collaborators and Investigators

• Sponsor: Capital Medical University

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2018
• Primary Completion (Anticipated): February 1, 2019
• Study Completion (Anticipated): May 1, 2019

Study Registration Dates

• First Submitted: August 28, 2016
• First Submitted That Met QC Criteria: August 28, 2016
• First Posted (Estimate): September 1, 2016

Study Record Updates

• Last Update Posted (Actual): June 20, 2018
• Last Update Submitted That Met QC Criteria: June 19, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: remote ischemic conditioning; r-tPA thrombolytic therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Ischemia
• Other Study ID Numbers: RIC-2016

Drug and device information, study documents

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