Application of Platelet Function Test in Prevention of Ischemic Events After Stent Placement in Intracranial Aneurysms (APISIA Trail)

A Study of Platelet Function Test in the Application of Prevention of Ischemic Events After Stent Placement in Intracranial Aneurysms

This study was designed to identify high platelet reactivity (HPR) who might have in-stent thrombosis in unruptured aneurysm with intracranial stent placement with light transmittance platelet aggregometry (LTA). For HPR patients, higher ischemic stroke rate maybe occurred, and we hypothesis that dose adjustment of aspirin and clopidogrel based on LTA monitoring maybe reduces the rate of ischemic stroke compared to a standard strategy after intracranial stent implantation at early periprocedural period and 1 month follow-up period.

Study Overview

• Status: Completed
• Conditions: Stents; Unruptured Intracranial Aneurysm; Antiplatelet Drugs
• Intervention / Treatment: Drug: Aspirin and clopidogrel/Ticagrelor; Device: Light transmittance aggregometry; Drug: Aspirin and clopidogrel/Ticagrelor

Detailed Description

For the patients of unruptured intracranial aneurysms with stent placement, standard antiplatelet therapy (100mg aspirin + 75mg clopidogrel) is considered to be the most effective antiplatelet regimen in reducing ischemic complications. However, despite the use of standard antiplatelet therapy, a number of patients continue to have ischemic events. A hypothesis is that high platelet reactivity (HPR) patients identified by platelet function test have higher ratio of the ischemic events, and dose adjustment of HPR patients reduces the rate of the ischemic complications at early periprocedural period and follow-up period.

Objectives: The study aim to evaluated the superiority of the strategy of platelet function test(Monitoring Arm) with the modified strategy in HPR patients compared to the standard strategy (Conventional Arm) whether reduce the primary endpoint after intracranial stent implantation at early periprocedural period (7 days) and 1 months follow-up period.

• Study Type: Interventional
• Enrollment (Actual): 314
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • 北京市
    • Beijing, 北京市, China, 100050
      • Beijing Neurosurgical Institute and Beijing Tiantan Hospital

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:

1. Age 18 - 80, male or non-pregnant female;
2. patients have unruptured aneurysm who plan to undergo intracranial stent placement;
3. patients with less than 2 of modified Rankin scale score at the day of enrollment;
4. patients who is able to understand the objective of the trial, agrees and signs the written informed consent form.

Exclusion Criteria:

1. The complications related to operation or material quality, such as guidewire pierces out blood vessel, coil herniation, incompletely opened stent, etc;
2. Simultaneous treatment of other cerebrovascular diseases, such as intracranial arteriovenous malformation, Intracranial arteriovenous fistula, etc;
3. Patient with history of hypersensitivity of aspirin, clopidogrel, or ticagrelor;
4. Patients with preoperative prophylactic use of tirofiban;
5. Patients with a high possibility of active bleeding, such as symptomatic intracranial hemorrhage or active gastric ulcer; or patients with coagulopathy;
6. Patients with thrombocytopenia (platelet count <100,000/mm3 within three months before enrollment);
7. patient using anticoagulant;
8. Pregnant or lactating women;
9. Patients with malignant diseases, such as liver disease, kidney disease, congestive heart failure, malignant tumors, etc;
10. Poor compliance patients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Monitoring Arm; Randomization: based on light transmittance aggregometry, modified dose of antiplatelet therapy(aspirin and ticagrelor) was used for high platelet reactivity(HPR) patients with intracranial stent placement, and standard antiplatelet regimen(aspirin and clopidogrel) was used in non-HPR patients.	Drug: Aspirin and clopidogrel/Ticagrelor; The modification of aspirin and clopidogrel/ticagrelor maintenance doses based on a biomarker assays.; Device: Light transmittance aggregometry; point-of-care method to assess platelet function by light transmittance aggregometry.; Drug: Aspirin and clopidogrel/Ticagrelor; maintenance dose of aspirin, clopidogrel and ticagrelor.
EXPERIMENTAL: Conventional Arm; Randomization: without light transmittance aggregometry, standard antiplatelet regimen was used for unruptured aneurysm patients with intracranial stent.	Drug: Aspirin and clopidogrel/Ticagrelor; The modification of aspirin and clopidogrel/ticagrelor maintenance doses based on a biomarker assays.; Drug: Aspirin and clopidogrel/Ticagrelor; maintenance dose of aspirin, clopidogrel and ticagrelor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A thromboembolic event during the early periprocedural period (within 7 days after stent placement)	The thromboembolic events were assessed by clinical examination. The thromboembolic events was a composite of ischemic stroke, transient ischemic attack, stent thrombosis, urgent revascularization, myocardial infarction, cerebrovascular death.	within 7 days of patients' enrolled.

Secondary Outcome Measures

Outcome Measure	Time Frame
A thromboembolic event during the 1 month follow-up periods.	within 1 month of patients' enrolled.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major bleeding and minor bleeding	Bleeding complications were accorded to Thrombolysis in Myocardial Infarction (TIMI) bleeding criteria.	within 1 month of patients' enrolled.

Collaborators and Investigators

• Sponsor: Beijing Neurosurgical Institute

Publications and helpful links

General Publications

• Li W, Zhu W, Wang A, Zhang G, Zhang Y, Wang K, Zhang Y, Wang C, Zhang L, Zhao H, Wang P, Chen K, Liu J, Yang X. Effect of Adjusted Antiplatelet Therapy on Preventing Ischemic Events After Stenting for Intracranial Aneurysms. Stroke. 2021 Dec;52(12):3815-3825. doi: 10.1161/STROKEAHA.120.032989. Epub 2021 Sep 20.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2019
• Primary Completion (ACTUAL): July 20, 2020
• Study Completion (ACTUAL): August 13, 2020

Study Registration Dates

• First Submitted: June 16, 2019
• First Submitted That Met QC Criteria: June 16, 2019
• First Posted (ACTUAL): June 18, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 9, 2020
• Last Update Submitted That Met QC Criteria: September 7, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: high platelet reactivity; Platelet function test; light transmittance platelet aggregometry
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Arterial Diseases; Aneurysm; Intracranial Aneurysm; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Ticagrelor; Clopidogrel
• Other Study ID Numbers: BNI-2019002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No