Combining Aspirin With Ticagrelor or Cilostazol in Large-vessel Minor Stroke or TIA

Combining Aspirin With Ticagrelor or Cilostazol in Large-vessel Minor Stroke or TIA, a Randomized Controlled Trial

Along with the current clinical trial, the efficacy and safety of a 180 mg loading dose of ticagrelor administered within 24 hours of the first-ever large-vessel minor stroke or TIA compared to 200mg cilostazol were assessed through NIHSS, mRS, and possible adverse effects.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke
• Intervention / Treatment: Drug: Ticagrelor 90 MG; Drug: Aspirin 75mg; Drug: Aspirin 75mg; Drug: Cilostazol 100 MG

Detailed Description

The investigators conducted a single-blinded randomized controlled trial after the ethics committee of the faculty of medicine at Kafr el-Sheik University approved it.

The investigators got written informed consent from all eligible patients or their first order of kin before randomization.

The study will be composed of 2 arms ticagrelor arm, which consisted of 450 patients who received a 180mg loading dose followed by 90 mg twice daily from the 2nd to the 90th day), and the cilostazol arm, consisting of 450 patients who received (a 200mg loading dose during the first 24 hours of stroke onset followed by 100mg twice daily from the 2nd day to the 90th day),

Study Procedures:

Every patient in our study will undergo:

Clinical workup: History, clinical assessment & NIHSS were recorded on admission, day 7, and the Modified Rankin Scale as a follow-up after one week and 3 months.

Detection of Risk Factors & Profiles:

Echocardiography TTE: in indicated patients ECG Monitoring: daily ECG monitoring will be performed in indicated patients. 3- Carotid Duplex: carotid duplex in indicated patients.

4- ESR & Lipid Profile& liver functions: All will be tested routinely for all patients.

Imaging Follow-UP Non-contrast CT brain on admission Day 2 MRI: after two days of admission, all the patients in this study will have a brain MRI (stroke protocol; T1W, T2W, FLAIR, DWI, T2 Echo Gradient, MRA of all intra-cerebral vessels).

CT brain: Any patient with unexplained clinical deterioration at any time throughout his/her hospital stay will be urgently imaged by CT.

Primary End Point:

The primary efficacy outcome was the rate of new stroke at 90 days, and the primary safety outcome was the rate of drug hemorrhagic complications using the PLATO bleeding definition.

• Secondary End Point: The secondary efficacy outcomes were to evaluate the rates of patients who achieved a significant reduction in NIHSS (decrease of four points or more) at the seventh day or discharge compared to baseline, the rates of a favorable outcome with (mRS = 0-2) after one week and after 90 days in a face-to-face interview in the outpatient clinic, rates of a composite of recurrent stroke, myocardial infarction and death due to vascular events after 90 days of follow-up, while the secondary safety outcome was the rate of treatment-related adverse effects assessed by a follow-up questionnaire

• Study Type: Interventional
• Enrollment (Estimated): 900
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: mohamed G. Zeinhom, MD; Phone Number: 2001009606828; Email: mohamed_gomaa@med.kfs.edu.eg
• Study Contact Backup: Name: sherihan R. ahmed, MD; Phone Number: 2001113432342; Email: sherihan_rezq@med.kfs.edu.eg

Study Locations

• Egypt
  • Cairo, Egypt, 22514
    • Recruiting
    • El-Sahel Teaching Hospital
    • Contact: Mohamed Ismaiel, MSc; Phone Number: 201125046663; Email: elkashefneuro@gmail.com
    • Principal Investigator: Mohamed Ismaiel, MSc
  • Kafr ash Shaykh, Egypt, 33511
    • Recruiting
    • Kafr Elsheikh University Hospital
    • Contact: mohamed G. Zeinhom, MD; Phone Number: 2001009606828; Email: mohamed_gomaa@med.kfs.edu.eg
    • Contact: sherihan R. ahmed, MD; Phone Number: 2001007481842; Email: sherihan_rezq@med.kfs.edu.eg
    • Principal Investigator: sherihan R. ahmed, MD
    • Principal Investigator: Mohamed G. Zeinhom, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• the investigators included both genders with eligible ages ranging between 18-75 years, with the first-ever presentation with large-vessel minor ischemic stroke or TIA who received antiplatelet treatment within the first 24 hours of the onset of ischemic stroke. Patients are not eligible for rt-PA treatment

Exclusion Criteria:

• The investigators excluded patients who had not been followed up on for 90 days after enrollment, those with NIHSS < 5 or who had rapidly resolving symptoms before imaging results, and patients with a known history of persistent or recurrent CNS pathology (e.g., epilepsy, meningioma, multiple sclerosis, history of head trauma with a residual neurological deficit).

The investigators excluded patients who had clinical seizures at the onset of their stroke, as well as those who had symptoms of any major organ failure, active malignancies, or an acute myocardial infarction within the previous six weeks, and those who were on warfarin, regular ticagrelor during the week before admission, or chemotherapy within the previous year.

The investigators excluded patients with active peptic ulcers, GIT surgery, bleeding history within the last year, and those with a history of major surgery within the last three months.

The investigators ruled out our trial patients who had a known allergy to the study drugs and those with INR > 1.4 or P.T. >18 or blood glucose level < 50 or > 400 mg/DL or blood pressure < 90/60 or > 185/110 mmHg on admission or Platelets < 100,000.

The investigators excluded pregnant and lactating patients and those with stroke due to venous thrombosis and stroke following cardiac arrest or profuse hypotension ineligible for our trial.

Patients with contraindications to the study drugs were excluded.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ticagrelor and aspirin arm; The ticagrelor arm will receive (a 180 mg loading dose of cilostazol during the first 24 hours of stroke onset, followed by 90 mg twice daily from the 2nd day to the 90th day) and an open-label loading 300 mg aspirin, followed by a maintenance dose of 75 mg aspirin.	Drug: Ticagrelor 90 MG; The ticagrelor arm will receive (a 180mg loading dose of cilostazol during the first 24 hours of stroke onset, followed by 90mg once daily from the 2nd day to the 90th day) and an open-label loading 300 mg aspirin, followed by a maintenance dose of 75 mg aspirin; Other Names: group A; Drug: Aspirin 75mg; The ticagrelor arm will receive (a 180mg loading dose of cilostazol during the first 24 hours of stroke onset, followed by 90mg once daily from the 2nd day to the 90th day) and an open-label loading 300 mg aspirin, followed by a maintenance dose of 75 mg aspirin; Other Names: group A; Drug: Aspirin 75mg; The cilostazol arm will receive (a 200 mg loading dose of clopidogrel during the first 24 hours of stroke onset, followed by 100 mg twice daily from the 2nd day to the 90th day) and open-label loading 300 mg aspirin, followed by a maintenance dose of 75 mg aspirin.; Other Names: group B
Active Comparator: cilostazol and aspirin; The cilostazol arm will receive (a 200 mg loading dose of cilostazol during the first 24 hours of stroke onset, followed by 100 mg twice daily from the 2nd day to the 90th day) and open-label loading 300 mg aspirin, followed by a maintenance dose of 75 mg aspirin.	Drug: Aspirin 75mg; The ticagrelor arm will receive (a 180mg loading dose of cilostazol during the first 24 hours of stroke onset, followed by 90mg once daily from the 2nd day to the 90th day) and an open-label loading 300 mg aspirin, followed by a maintenance dose of 75 mg aspirin; Other Names: group A; Drug: Aspirin 75mg; The cilostazol arm will receive (a 200 mg loading dose of clopidogrel during the first 24 hours of stroke onset, followed by 100 mg twice daily from the 2nd day to the 90th day) and open-label loading 300 mg aspirin, followed by a maintenance dose of 75 mg aspirin.; Other Names: group B; Drug: Cilostazol 100 MG; The cilostazol arm will receive (a 200 mg loading dose of clopidogrel during the first 24 hours of stroke onset, followed by 100 mg twice daily from the 2nd day to the 90th day) and open-label loading 300 mg aspirin, followed by a maintenance dose of 75 mg aspirin.; Other Names: group B

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of drug-related hemorrhagic complications	the rate of drug hemorrhagic complications which was evaluated using the PLATO bleeding definition which classified hemorrhagic complications into three types as follows: Major bleeding which had one or more of the following criteria: fatal bleeding, intracranial, intrapericardial, bleeding associated with reduction of hemoglobin > 3-5 g/dl, bleeding required transfusion of two to four units whole blood or PRBCs, bleeding produced hypovolemic shock or severe hypotension that required pressor or surgery; Minor bleeding that required medical intervention to stop or treat bleeding: Minimal bleeding: any bleeding that did not require intervention or treatment such as bruising, bleeding gums, oozing from injection sites.	90 days
rate of new stroke	Rates of new stroke occur within three months of treatment. The investigators will perform follow-ups of the patient during visits to the outpatient clinic, and brain CT and/ or MRI will be done if there is suspicion of a new stroke.	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
value of Modified Rankin Scale(mRS) at three months	mRS Measures the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability; its value ranges from 0 to 6; the lower the score, the better the stroke outcome. A favorable stroke outcome is considered with mRS value equal to two or less.	3 months
rate of composite recurrent stroke, myocardial infarction, and death due to vascular events	Rates of new stroke, TIA, myocardial infarction, or death from vascular events within three months of treatment, the investigators will perform follow-ups of the patient during visits to the outpatient clinic and perform needed investigations such as brain imaging, Electrocardiography, arterial and venous duplex ultrasound imaging.	3 months
rate of drug adverse effects	all side effects related to the medications of our study will be reported	3 months

Collaborators and Investigators

• Sponsor: Kafrelsheikh University
• Collaborators: El-Sahel Teaching Hospital
• Investigators: Principal Investigator: mohamed G. Zeinhom, MD, neurology department kafr el-sheikh university; Principal Investigator: Mohamed Ismaiel, MSc, neurology department El-sahel teaching hospital

Publications and helpful links

General Publications

• Paciaroni M, Ince B, Hu B, Jeng JS, Kutluk K, Liu L, Lou M, Parfenov V, Wong KSL, Zamani B, Paek D, Min Han J, Del Aguila M, Girotra S. Benefits and Risks of Clopidogrel vs. Aspirin Monotherapy after Recent Ischemic Stroke: A Systematic Review and Meta-Analysis. Cardiovasc Ther. 2019 Dec 1;2019:1607181. doi: 10.1155/2019/1607181. eCollection 2019.
• Lipton RB, Liberman JN, Kolodner KB, Bigal ME, Dowson A, Stewart WF. Migraine headache disability and health-related quality-of-life: a population-based case-control study from England. Cephalalgia. 2003 Jul;23(6):441-50. doi: 10.1046/j.1468-2982.2003.00546.x.

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2024
• Primary Completion (Estimated): September 19, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: September 8, 2024
• First Submitted That Met QC Criteria: September 8, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Estimated): September 18, 2025
• Last Update Submitted That Met QC Criteria: September 12, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: cilostazol; ticagrlor; large-vessel stroke
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Purines; Phenols; Benzene Derivatives; Nucleosides; Ribonucleosides; Quinolines; Salicylates; Hydroxybenzoates; Adenosine; Purine Nucleosides; Tetrazoles; Ticagrelor; Cilostazol; Aspirin
• Other Study ID Numbers: 2309881671459145

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All the data that support the findings of this research will be available from the corresponding author M. Zeinhom upon reasonable request.

Drug and device information, study documents

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