Endovascular Treatment and RIPC in Acute Ischemic Stroke (EnTRIPS)

• ClinicalTrials.gov Identifier: NCT04581759
• Recruitment Status: Recruiting
• First Posted: October 9, 2020
• Last Update Posted: April 30, 2021
• Sponsor: First Affiliated Hospital Xi'an Jiaotong University
• Collaborators: Second Affiliated Hospital of Xi'an Jiaotong University; Shaanxi Provincial People's Hospital; Xijing Hospital; Tang-Du Hospital; Xi'an No.3 Hospital; Xi'an Gaoxin Hospital
• Information provided by (Responsible Party): First Affiliated Hospital Xi'an Jiaotong University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Acute Ischemic Stroke; Endovascular Treatment	Device: RIPC device (IPC-906X); Drug: foundational treatment	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Endovascular Treatment Combined With Remote Ischemic Postconditioning in Patients With Acute Ischemic Stroke Improves the Prognosis，a Multicenter, Randomized, Prospective Trial
• Actual Study Start Date: April 12, 2021
• Estimated Primary Completion Date: December 31, 2022
• Estimated Study Completion Date: February 28, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Modified Rankin scale (mRS) [ Time Frame: 7days, 90 days and 180 days after the surgery and at discharge ]
   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）

Secondary Outcome Measures :

1. The change of NIHSS score [ Time Frame: 7days, 90 days and 180 days after the surgery and at discharge ]
   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）
2. The change of Barthel Index [ Time Frame: 7days, 90 days and 180 days after the surgery and at discharge ]
   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）
3. The change of Montreal Cognitive Assessment (MoCA) score [ Time Frame: 7days, 90 days and 180 days after the surgery and at discharge ]
   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）
4. The change of MMSE score [ Time Frame: 7days, 90 days and 180 days after the surgery and at discharge ]
   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）
5. The change of inflammatory indicators [ Time Frame: before ET, 24 hours and 7 days after the surgery ]
   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）
6. The change of angiogenic factors [ Time Frame: before ET, 24 hours and 7 days after the surgery ]
   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）
7. The change of hemoglobin and Blood viscosity [ Time Frame: up to 7 days after the surgery ]
   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）
8. Postoperative hemorrhagic transformation [ Time Frame: 72 hours after ET and hospitalization ]
   The proportion of patients with postoperative hemorrhagic transformation, based on CT scan and symptom
9. The change of MRI FLAIR Fazekas score [ Time Frame: the changs from within 7 days to 90 days after the surgery ]
   Cerebral white matter demyelination measured by MRI FLAIR Fazekas score，（Notes:Fazekas score from 0-6. higher scores mean worse outcome）
10. The change of blood flow velocity [ Time Frame: the changs from 24 hours after ET to 7 days after the surgery ]
    Vascular blood flow velocity measured by transcranial doppler （TCD） examination
11. Vascular resistance [ Time Frame: the changs from 24 hours after ET to 7 days after the surgery ]
    Vascular resistance measured by TCD examination
12. mortality rate [ Time Frame: up to 90 days and 180 days ]
    90-days and 180-days mortality rate
13. recurrence rate of cerebrovascular disease [ Time Frame: up to 90 days and 180 days ]
    90-days and 180-days recurrence rate of cerebrovascular disease
14. blood pressure [ Time Frame: up to 7days ]
    The effect of RIPC on blood pressure
15. heart rate [ Time Frame: up to 7days ]
    The effect of RIPC on heart rate

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Guogang Luo, MD; 0086-13991974085; lguogang@163.com

Contact: Meng Wei, MD; 0086-15991748135; 67183723@qq.com

Locations

China, Shaanxi

First Affiliated Hospital of Xi'an Jiaotong University; Recruiting

Xi'an, Shaanxi, China, 710061

Contact: Guogang Luo, doctor 0086-13991974085 lguogang@163.com

Sponsors and Collaborators

First Affiliated Hospital Xi'an Jiaotong University

Second Affiliated Hospital of Xi'an Jiaotong University

Shaanxi Provincial People's Hospital

Xijing Hospital

Tang-Du Hospital

Xi'an No.3 Hospital

Xi'an Gaoxin Hospital

More Information

• Responsible Party: First Affiliated Hospital Xi'an Jiaotong University
• ClinicalTrials.gov Identifier: NCT04581759
• Other Study ID Numbers: XJTU1AF2020LSK-174
• First Posted: October 9, 2020
• Last Update Posted: April 30, 2021
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol
• Time Frame: 12/31/2023, for 1 year

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Stroke; Ischemic Stroke; Cerebral Infarction; Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Brain Infarction; Brain Ischemia; Infarction; Necrosis