The Impact of NBP on the Collateral Circulation in ICA/M1 Occlusion (INCIMO)

The Impact of NBP on the Collateral Circulation in Acute Acute Internal Carotid Artery(ICA)/Middle Cerebral Artery(M1) Occlusion

Stroke is the first leading cause of death in China, and is responsible for almost 22.4% of deaths. In approximately 80% of cases stroke is ischaemic, i.e. caused by disruption of blood flow to part of the brain from an acute arterial occlusion. Survival of penumbral tissue distal to an arterial occlusion depends on collateral circulation via the Circle of Willis and leptomeningeal anastomises. Collateral flow is dynamic and failure is associated with infarct growth. The presence of adequate collaterals has been shown to be associated with age, history of statin use, and non-hypertension. Dl-3-n-butylphthalide (NBP), isolated from the seeds of celery, and found to exert protective effects against ischemic brain and increase leptomeningeal blood flow. This study investigate whether NBP injection prescribed during acute stroke will have a significant effect to improve collateral circulation in patients of anterior circulation occlusion.

Study Overview

• Status: Completed
• Conditions: Anterior Cerebral Circulation Infarction; Cerebrovascular Occlusion; Collateral Blood Circulation
• Intervention / Treatment: Drug: NBP

• Study Type: Interventional
• Enrollment (Actual): 311
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • The Second Affiliated Hospital of Zhejiang 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. Men or women ≥ 18 years old;
2. Acute occlusion of M1 or intracranial internal carotid artery within 72 hours;
3. For patients who receive recombinant tissue-type plasminogenactivator therapy, the arterial occlusive lesion scale of 24-72 hours post-thrombolysis imaging should be 0 or 1;
4. Ischemic stroke with National Institutes of Health Stroke Scale ≥ 4;
5. Baseline mRS before this stroke onset less than 2;
6. Able and willing to comply with study requirements;
7. Signed informed consent by patients self or legally authorized representatives.

Exclusion Criteria:

1. Cerebral hemorrhage;
2. Posterior circulation infarction;
3. Severe tendency of hemorrhage, such as thrombocytopenia, leukemia, allergic purpura;
4. Currently using urinary kallidinogenase or alprostadil;
5. Be allergic to NBP or celery;
6. Impaired liver function (alanine aminotransferase or glutamic oxalacetic transaminase ≥ 3×upper limit of normal) or renal function (serum creatinie ≥ 1.5mg/dl);
7. Patients with evidence of severe congestive heart failure or history of end-stage cardiovascular disease (e.g. congestive heart failure New York Heart Association Class III or IV);
8. Metastatic neoplasm or multiple organ failure;
9. Pregnancy or breastfeeding;
10. History of mental instability or dementia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: NBP in thrombolysis group; NBP 25mg bid for 2 weeks administered after 24 hours after receiving recombinant plasminogenactivator(rt-PA) thrombolysis	Drug: NBP
EXPERIMENTAL: NBP group; NBP 25mg bid for 2 weeks administered for the patients who do not receive rt-PA	Drug: NBP
NO_INTERVENTION: Control group; Control group not receiving rt-PA thrombolysis, receiving basic therapy for acute stroke, e.g. aspirin/clopidogrel and lipid-lowering therapy
NO_INTERVENTION: Control in thrombolysis group; Control group receiving rt-PA thrombolysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
the percentage of patients with modified Rankin Score (mRS) equivalent to or less than 2	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rLMC scale of Collateral circulation	We use regional leptomeningeal score(rLMC) score to measure collateral circulation.rLMC score is based on scoring pial and lenticulostriate arteries in 6 ASPECTS regions(M1-6) plus anterior cerebral artery region and basal ganglia. Pial arteries in the Sylvian sulcus are scored 0,2, or 4.	2 weeks, 3 months
NIHSS score		1 week, 2 weeks, 3 months
Hemorrhageic complications including intracranial, digestive tract		2 weeks, 3 months
New stroke or transient ischemic attack(TIA)		3 months
complete blood count		3 months

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Study Chair: Min Lou, Ph.D, M.D., Second Affiliated Hospital of Zhejiang University, School of Medicine

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (ACTUAL): September 1, 2016
• Study Completion (ACTUAL): December 30, 2019

Study Registration Dates

• First Submitted: October 22, 2015
• First Submitted That Met QC Criteria: October 30, 2015
• First Posted (ESTIMATE): November 3, 2015

Study Record Updates

• Last Update Posted (ACTUAL): March 31, 2020
• Last Update Submitted That Met QC Criteria: March 27, 2020
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Stroke; Infarction; Cerebrovascular Disorders; Brain Infarction
• Other Study ID Numbers: SAHZJUNeuro