Ticagrelor Versus Cilostazol in Large-vessel Ischemic Stroke

NCT ID: NCT06202755

Last Updated: 2024-08-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 580 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-30
• Study Completion Date: 2025-07-12

Brief Summary

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

Detailed Description

The investigators conducted a single-blinded randomized controlled trial between March 2024 and June 2025 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 290 patients who received a 180 mg loading dose followed by 90 mg b.i.d from the 2nd to the 90th day), and the cilostazol arm consisting of 290 patients who received (a 200 mg loading dose during the first 24 hours of stroke onset followed by 100 mg 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 2 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

Conditions

Ischemic Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

ticagrelor arm

The ticagrelor arm will receive (180 mg loading dose during the first 24 hours of stroke onset, followed by 90 mg b.i.d from the 2nd to the 90th day)

Group Type: ACTIVE_COMPARATOR

Ticagrelor 90 MG

Intervention Type: DRUG

Efficacy and safety of 180 mg loading dose of ticagrelor administered within 24 hours of first-ever ischemic stroke followed by 90 mg bid for 3 months will be assessed through NIHSS, mRS, duration of hospital stay, new ischemic stroke, and possible adverse effects.

cilostazol arm

The cilostazol arm will receive (a 200 mg loading dose during the first 24 hours of stroke onset, followed by 100 mg twice daily from the 2nd day to the 90th day)

Group Type: ACTIVE_COMPARATOR

Cilostazol 100 MG

Intervention Type: DRUG

Efficacy and safety of 200 mg clopidogrel followed by 100 mg twice daily for 3 months will be assessed through NIHSS, mRS, duration of hospital stay, new ischemic stroke, and possible adverse effects.

Interventions

Ticagrelor 90 MG

Efficacy and safety of 180 mg loading dose of ticagrelor administered within 24 hours of first-ever ischemic stroke followed by 90 mg bid for 3 months will be assessed through NIHSS, mRS, duration of hospital stay, new ischemic stroke, and possible adverse effects.

Intervention Type: DRUG

Cilostazol 100 MG

Efficacy and safety of 200 mg clopidogrel followed by 100 mg twice daily for 3 months will be assessed through NIHSS, mRS, duration of hospital stay, new ischemic stroke, and possible adverse effects.

Intervention Type: DRUG

Other Intervention Names

group A; group B

Eligibility Criteria

Inclusion Criteria

• the investigators included both genders with eligible ages ranging between 18-75 years, with the first-ever presentation with acute large-vessel ischemic stroke who received antiplatelet treatment within the first 24 hours of the onset of ischemic stroke. Patients with previous transient ischemic attacks (TIA) were not excluded from the study. Patients are not eligible for rt-PA treatment

Exclusion Criteria

• he investigators excluded patients who had not been followed up on for 90 days after enrollment, those with NIHSS ≤ 3 or ≥ 25 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 of 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kafrelsheikh University

OTHER

Sponsor Role: lead

Responsible Party

Mohamed G. zeinhom, MD

principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

mohamed G. Zeinhom, MD

Role: STUDY_DIRECTOR

neurology department kafr el-sheikh university

Locations

Kafr Elsheikh University Hospital

Kafr ash Shaykh, , Egypt

Site Status: RECRUITING

Countries

Egypt

Central Contacts

mohamed G Zeinhom, MD

Role: CONTACT

mohamed_gomaa@med.kfs.edu.eg

2001009606828

sherihan R. ahmed, MD

Role: CONTACT

sherihanrezk2016@gmail.com

2001113432342

Facility Contacts

mohamed G. Zeinhom, MD

Role: primary

mohamed_gomaa@med.kfs.edu.eg

2001009606828

sherihan R ahmed, MD

Role: backup

sherihanrezk2016@gmail.com

2001007481842

References

Zeinhom MG, Aref HM, El-Khawas H, Roushdy TM, Shokri HM, Elbassiouny A. A pilot study of the ticagrelor role in ischemic stroke secondary prevention. Eur Neurol. 2022;85(1):50-55. doi: 10.1159/000518786. Epub 2021 Aug 30.

Reference Type: RESULT

PMID: 34515113 (View on PubMed)

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.

Reference Type: RESULT

PMID: 31867054 (View on PubMed)

Meyer DM, Albright KC, Allison TA, Grotta JC. LOAD: a pilot study of the safety of loading of aspirin and clopidogrel in acute ischemic stroke and transient ischemic attack. J Stroke Cerebrovasc Dis. 2008 Jan-Feb;17(1):26-9. doi: 10.1016/j.jstrokecerebrovasdis.2007.09.006.

Reference Type: RESULT

PMID: 18190818 (View on PubMed)

Gachet C, Stierle A, Cazenave JP, Ohlmann P, Lanza F, Bouloux C, Maffrand JP. The thienopyridine PCR 4099 selectively inhibits ADP-induced platelet aggregation and fibrinogen binding without modifying the membrane glycoprotein IIb-IIIa complex in rat and in man. Biochem Pharmacol. 1990 Jul 15;40(2):229-38. doi: 10.1016/0006-2952(90)90683-c.

Reference Type: RESULT

PMID: 2375765 (View on PubMed)

Other Identifiers

239888

Identifier Type: -

Identifier Source: org_study_id