Endovascular Treatment and RIPC in Acute Ischemic Stroke (EnTRIPS)

Endovascular Treatment Combined With Remote Ischemic Postconditioning in Patients With Acute Ischemic Stroke Improves the Prognosis，a Multicenter, Randomized, Prospective Trial

Endovascular treatment（ET）is an effective therapy for acute ischemic stroke(AIS) with great vessel obstruction. However, acute complications such as high postoperative perfusion injury, hemorrhagic transformation and restenosis resulted in functional independence in only about 50% of patients 90 days after interventional surgery. Therefore, it is very important to protect the neurologic function after emergency endovascular treatment. The investigators' previous studies have shown that combined with intravenous thrombolytic therapy and remote postconditioning（RIPC）can significantly improve the neurological impairment and short-term and long-term prognosis in patients with acute stroke. In this multicenter, randomized controlled trial, the investigators assumed patients with acute ischemic stroke who had successfully revascularization after ET might benefit from RIPC as well. Patients in the RIPC group had five cycles of 5-min cuff inflation followed by 3-min deflation to the bilateral upper arm after ET. The primary endpoint measure was the proportion of patients with a favorable recovery of nerve function deficient assessed by Modified Rankin Scale （mRS≤2） 90 days after surgery. Secondary endpoints included the following: (1) Symptom endpoints: Neurological intelligence and function scores, postoperative hemorrhagic transformation rate, etc. (2) Blood index test: postoperative inflammatory factors, neuron-specific enolase (NSE) and other indicators. (3) Imaging endpoints: MRI-FLAIR , TCD, etc.

Study Overview

• Status: Recruiting
• Conditions: Acute Ischemic Stroke; Endovascular Treatment
• Intervention / Treatment: Device: RIPC device (IPC-906X); Drug: foundational treatment

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Guogang Luo, MD; Phone Number: 0086-13991974085; Email: lguogang@163.com
• Study Contact Backup: Name: Meng Wei, MD; Phone Number: 0086-15991748135; Email: 67183723@qq.com

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • Recruiting
      • First Affiliated Hospital of Xi'an Jiaotong University

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. acute ischemic stroke（AIS） patients with large vessel occlusion (internal carotid artery system and vertebral basilar artery system) within 24 hours after onset, endovascular treatment (mechanical thrombotomy, intra-arterial thrombolysis, balloon dilatation or stent angioplastyand) successful opening were performed, and the definition of successful opening was defined by Modified Thrombolysis standard [Modified Thrombolysis in Cerebral infarction, mTICI]≥ 2B，The standards of endovascular interventional treatment are in line with the indications and contraindications formulated in the Chinese Guidelines for the Early Treatment of Acute Ischemic Stroke 2018；
2. Modified Rankin scale score (mRS) ≤1 before onset:
3. The Alberta Stroke Program Early CT score (ASPECTS)≥6 on admission;
4. National Institute of Health Stroke Scale (NIHSS) score ≥6 on admission;
5. Provision of written informed consent.

Exclusion Criteria:

1. CT or MRI scan showed significant midline deviation and the mass effect;
2. Glasgow(GCS) score ≤8 on admission;
3. failure to accomplish 3-months and 6-months follow up;
4. Severe cardiac, liver, or kidney disease, malignancy, severe coagulation dysfunction, severe anemia and systemic organ dysfunction;
5. Pregnant or nursing women, or patients with moderate to severe mental disorders or dementia;
6. Severe soft tissue injuries, fractures, thrombosis and other known peripheral vascular lesions of the upper limbs，active visceral hemorrhage, acute stage of fundus hemorrhage, cerebral aneurysm or cerebral arteriovenous malformation, and other unsuitable for bilateral upper arm compression.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: RIPC; Patients in the RIPC group not only receive foundational treatment but also have five cycles of 5-min cuff inflation followed by 3-min deflation to the bilateral upper arm using a RIPC device (IPC-906X; Beijing Renqiao Institute of Neuroscience, Beijing, China) after endovascular treatment while in-hospital.	Device: RIPC device (IPC-906X); Patients in the RIPC group will have five cycles of 5-min cuff inflation followed by 3-min deflation to the bilateral upper arm twice a day after Mechanical Thrombectomy.; Drug: foundational treatment; foundational treatment, including free radical elimination in the acute stage, blood pressure and blood glucose stabilization, and antiplatelet (aspirin or/and clopidogrel ) and lipid-lowering (statins) drugs
SHAM_COMPARATOR: foundational treatment group (FT); Patients in the FT group only receive foundational treatment, including free radical elimination in the acute stage, blood pressure and blood glucose stabilization, and antiplatelet (aspirin or/and clopidogrel,100-300mg/d) and lipid-lowering (atorvastatin 20-60mg/d,rosuvastatin 10-20mg/d) drugs, during the study period without remote ischemic postconditioning after endovascular treatment.	Drug: foundational treatment; foundational treatment, including free radical elimination in the acute stage, blood pressure and blood glucose stabilization, and antiplatelet (aspirin or/and clopidogrel ) and lipid-lowering (statins) drugs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin scale (mRS)	The percentage of patients with a favorable outcome from baseline at 90 days and 180 days postoperatively, defined as a score of 0 or 2 on the modified Rankin scale (mRS)（Notes:mRS score from 0-6, higher scores mean worse outcome）	7days, 90 days and 180 days after the surgery and at discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change of NIHSS score	The percentage of functional recovery from baseline at 90 days and 180 days postoperatively, as measured by the National Institute of Health Stroke Scale, short for NIHSS（Notes:NIHSS score from 0-42. higher scores mean worse outcome）	7days, 90 days and 180 days after the surgery and at discharge
The change of Barthel Index	The change of functional recovery from baseline at 90 days and 180 days postoperatively, as measured by the Barthel Index （Notes:Barthel Index score from 0-100. higher scores mean better outcome）	7days, 90 days and 180 days after the surgery and at discharge
The change of Montreal Cognitive Assessment (MoCA) score	The change of cognitive recovery from baseline at 90 days and 180 days postoperatively, as measured by the MoCA （Notes:MoCA score from 0-30. higher scores mean better outcome）	7days, 90 days and 180 days after the surgery and at discharge
The change of MMSE score	The change of cognitive recovery from baseline at 90 days and 180 days postoperatively, as measured by the MMSE（Notes:MMSE score from 0-30. higher scores mean better outcome）	7days, 90 days and 180 days after the surgery and at discharge
The change of inflammatory indicators	Peripheral venous blood was drawn before Endovascular Treatment(ET) and 24 hours and 7 days postoperatively to determine the effect of repeated RIPC on anti-inflammatory (hIL-1β、hIL-2R、hIL-6、hIL8、hIL-10、S100-β、TNF-α) （Notes: unit ng/ml）	before ET, 24 hours and 7 days after the surgery
The change of angiogenic factors	Peripheral venous blood was drawn before ET and 24 hours and 7 days postoperatively to determine the effect of repeated RIPC on vascular (VEGF、bFGF、EPO、HIF-1α、BDNF) and other pathways (S100B、NSE)（Notes: unit ng/ml）	before ET, 24 hours and 7 days after the surgery
The change of hemoglobin and Blood viscosity	Peripheral venous blood was drawn before ET and 24 hours and 7 days postoperatively to determine the effect of repeated RIPC on Hb and Blood viscosity（Notes: unit g/L , mPa.s）	up to 7 days after the surgery
Postoperative hemorrhagic transformation	The proportion of patients with postoperative hemorrhagic transformation, based on CT scan and symptom	72 hours after ET and hospitalization
The change of MRI FLAIR Fazekas score	Cerebral white matter demyelination measured by MRI FLAIR Fazekas score，（Notes:Fazekas score from 0-6. higher scores mean worse outcome）	the changs from within 7 days to 90 days after the surgery
The change of blood flow velocity	Vascular blood flow velocity measured by transcranial doppler （TCD） examination	the changs from 24 hours after ET to 7 days after the surgery
Vascular resistance	Vascular resistance measured by TCD examination	the changs from 24 hours after ET to 7 days after the surgery
mortality rate	90-days and 180-days mortality rate	up to 90 days and 180 days
recurrence rate of cerebrovascular disease	90-days and 180-days recurrence rate of cerebrovascular disease	up to 90 days and 180 days
blood pressure	The effect of RIPC on blood pressure	up to 7days
heart rate	The effect of RIPC on heart rate	up to 7days

Collaborators and Investigators

• Sponsor: First Affiliated Hospital Xi'an Jiaotong University
• Collaborators: Xijing Hospital; Shaanxi Provincial People's Hospital; Second Affiliated Hospital of Xi'an Jiaotong University; Tang-Du Hospital; Xi'an Gaoxin Hospital; Xi'an No.3 Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 12, 2021
• Primary Completion (ANTICIPATED): April 30, 2023
• Study Completion (ANTICIPATED): October 30, 2023

Study Registration Dates

• First Submitted: September 9, 2020
• First Submitted That Met QC Criteria: October 3, 2020
• First Posted (ACTUAL): October 9, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 10, 2022
• Last Update Submitted That Met QC Criteria: May 6, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction
• Other Study ID Numbers: XJTU1AF-CRF-2020-015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: 12/31/2023, for 1 year
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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