Ticagrelor Versus Clopidogrel in Large Vessel Ischemic Stroke

Sponsor

Kafrelsheikh University (Other)

Overall Status

Recruiting

CT.gov ID

NCT06120725

Collaborator

(none)

580

Enrollment

Location

Arms

26.1

Anticipated Duration (Months)

22.2

Patients Per Site Per Month

Study Details

Study Description

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 300 mg clopidogrel were assessed through NIHSS, mRS, duration of hospital stay, and possible adverse effects.

Condition or Disease	Intervention/Treatment	Phase
Ischemic Stroke	Drug: Ticagrelor 90 MG Drug: Clopidogrel	Phase 3

Detailed Description

The investigators conducted an open-label randomized controlled trial between September 2021 and September 2023 after approval of the ethical committee of the faculty of medicine at Kafr el-Sheik University.

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; the ticagrelor arm consisted of 290 patients who received (a 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), and the Clopidogrel arm consisted of 150 patients, who received (a 300 mg loading dose during the first 24 hours of stroke onset followed by 75 mg once daily from the 2nd day to the 90th day), All the patients in the two groups received open-label aspirin at a loading dose of 75 to 300 mg, followed by 75 mg daily for 21 days.

Study Procedures:

Every patient in our study will undergo:

Clinical workup: History and clinical assessment & NIHSS recorded on admission, day 2 and day 7, and Modified Rankin Scale as a follow-up after one week and 3 months.

Detection of Risk Factors & Profiles:

Echocardiography& TOE: 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 safety of ticagrelor versus clopidogrel is the primary interest of this study. This will be assessed in both central hemorrhagic transformation and other probable side effects as follows:

Hemorrhagic transformation of the Infarct was determined by performing a follow-up C.T. brain scan after two days and after one week or discharge, and at 90 days to detect the hemorrhage; additionally, the European Cooperative Acute Stroke Study (ECASS) classification14 was used to detect the type of hemorrhagic transformation.

Complication Survey & Other Adverse Manifestations:

Peripheral Bleeding: assessed by the PLATO bleeding definition throughout 90 days Drug Allergy: All suspected allergic reactions will be reported.

Side effects: Both will be specifically assessed in all patients.

Secondary End Point: Efficacy of treatment assessed by NIHSS: All patients will be assessed with NIHSS on admission, second day, after 1 week, and/or discharge. Patients admitted for less than 1 week will be assessed only on discharge. The improvement will be counted only if there is a decrease in NIHSS score by 4 points or more Infarct Size Expansion: in case of clinical deterioration of the patient, the infarction size difference between 1st MRI and follow-up MRI diffusion studies will be calculated.

Modified Rankin Scale: this will be a parameter for the patient's outcome, assessed at the end of one week and 3 months, and we will categorize stroke as follows: fatal stroke [stroke with the subsequent score on the modified Rankin scale of 6], severe stroke [stroke with the subsequent score on the modified Rankin scale of 4 or 5], moderate stroke [stroke with the subsequent score on the modified Rankin scale of 2 or 3], mild stroke [stroke with the subsequent score on the modified Rankin scale of 0 or 1], TIA, and no stroke or TIA) Hospital Stay: Total hospital stay will be calculated in days for all patients. Additional analysis will involve the time of admission at the ICU and ward, Neurological Critical Unit, Stroke ward unit, or ICU referral.

new ischemic stroke at 90 days a composite of ischemic stroke, TIA, myocardial infarction, and death due to vascular complications at 90 days

Study Design

Study Type:

Interventional

Anticipated Enrollment :

580 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

We will conduct our open-label randomized controlled trial, which will contain 2 arms; the ticagrelor arm will receive (a 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), and the Clopidogrel arm will receive (300 mg loading dose during the first 24 hours of stroke onset followed by 75 mg once daily from the 2nd day to the 90th day). All the patients in the two groups will receive aspirin at a loading dose of 75 to 300 mg, followed by 75 mg daily for 21 days.We will conduct our open-label randomized controlled trial, which will contain 2 arms; the ticagrelor arm will receive (a 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), and the Clopidogrel arm will receive (300 mg loading dose during the first 24 hours of stroke onset followed by 75 mg once daily from the 2nd day to the 90th day). All the patients in the two groups will receive aspirin at a loading dose of 75 to 300 mg, followed by 75 mg daily for 21 days.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Ticagrelor Versus Clopidogrel in Large Vessel Ischemic Stroke, a Randomized Controlled Trial

Actual Study Start Date :

Sep 1, 2021

Actual Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Nov 5, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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) and aspirin at a loading dose of 75 to 300 mg, followed by 75 mg daily for 21 days.	Drug: 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.
Active Comparator: clopidogrel arm The clopidogrel arm will receive (a 300 mg loading dose during the first 24 hours of stroke onset followed by 75 mg once daily from the 2nd day to the 90th day) and aspirin at a loading dose of 75 to 300 mg, followed by 75 mg daily for 21 days.	Drug: Clopidogrel Efficacy and safety of 300 mg clopidogrel followed by 75 mg once daily for 3 months will be assessed through NIHSS, mRS, duration of hospital stay, new ischemic stroke, and possible adverse effects.

Arm

Intervention/Treatment

Active Comparator: 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) and aspirin at a loading dose of 75 to 300 mg, followed by 75 mg daily for 21 days.

Drug: 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.

Active Comparator: clopidogrel arm

The clopidogrel arm will receive (a 300 mg loading dose during the first 24 hours of stroke onset followed by 75 mg once daily from the 2nd day to the 90th day) and aspirin at a loading dose of 75 to 300 mg, followed by 75 mg daily for 21 days.

Drug: Clopidogrel

Efficacy and safety of 300 mg clopidogrel followed by 75 mg once daily for 3 months will be assessed through NIHSS, mRS, duration of hospital stay, new ischemic stroke, and possible adverse effects.

Outcome Measures

Primary Outcome Measures

Rate of Hemorrhagic transformation of the Infarct [90 days]
Hemorrhagic transformation of the Infarct was determined by performing a follow-up C.T. brain scan after two days, after one week or discharge, and at 90 days to detect the hemorrhagic infarction.
Rate of Peripheral Bleeding using PLATO classification [90 days]
Peripheral Bleeding: assessed by platelet inhibition and patient outcomes (PLATO) bleeding definition throughout 90 days PLATO bleeding definition categorizes bleeding into three types: Major: if the Bleeding has any of these criteria: Fatal Intracranial Intrapericardial :with cardiac tamponade Resulting in hypovolemic shock or severe hypotension that requires pressors or surgery Clinically overt or apparent Bleeding associated with a decrease in hemoglobin >5 g/dL Requiring transfusion of ≥4 U whole blood or PRBCs Significantly disabling (e.g., intraocular with permanent vision loss) Associated drop in hemoglobin of 3 to 5 g/dL Requiring transfusion of 2 to 3 U whole blood or PRBCs minor: Requires medical intervention to stop or treat bleeding minimal: any other bleeding
rate of drug adverse effects [90 days]
Drug adverse effects: all side effects related to the drugs of our study will be reported

Secondary Outcome Measures

Value of National Institute of Health Stroke Scale (NIHSS) after two days [2 days]
NIHSS is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke and aid in planning post-acute care disposition. It ranges from 0 to 42; the lower the score, the better the stroke condition. The improvement will be counted only if there is a decrease in NIHSS score by four points or more within two days of stroke onset.
Value of National Institute of Health Stroke Scale (NIHSS) after one week [7 days]
NIHSS is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke and aid in planning post-acute care disposition. It ranges from 0 to 42; the lower the score, the better the stroke condition. The improvement will be counted only if there is a decrease in NIHSS score by four points or more within one week of stroke onset.
value of Modified Rankin Scale (mRS) at one week [7 days]
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 favorable stroke outcome is considered with mRS value equals two or less.
value of Modified Rankin Scale(mRS) at three months [3 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 favorable stroke outcome is considered with mRS value equals two or less.
value of total hospital stay duration [90 days]
Total hospital stay will be calculated in days for all patients
rate of new ischemic stroke [90 days]
Rates of new ischemic 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 recurrence of ischemic stroke.
rate of vascular event [90 days]
Rates of new ischemic 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

the 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.