Ticagrelor Versus Clopidogrel in Ischemic Stroke. a Randomized Double-blinded Controlled Trial
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Kafrelsheikh University
- Enrollment
- 900
- Locations
- 1
- Primary Endpoint
- -the rate of new stroke in each group
Study Overview
Brief Summary
Along with the current clinical trial, the efficacy and safety of 180 mg loading dose of ticagrelor administered within the first 24 hours of first-ever ischemic stroke compared to 300 mg clopidogrel were assessed through NIHSS, mRS, duration of hospital stay, and possible adverse effects.
Detailed Description
The investigators will conduct a single-blinded randomized controlled trial between October 2022 and December 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 ticagrelor arm, which consisted of 450 patients who received a 180 mg loading dose followed by 90 mg b.i.d from the 2nd to the 90th day), and the Clopidogrel arm consisting of 450 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)
Study Procedures:
Every patient in our study will undergo:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Investigator, Outcomes Assessor)
Masking Description
An independent statistician generated a blocked randomization sequence using computer-generated random numbers; in a one-to-one ratio, participants were randomly assigned to receive either loading doses of ticagrelor and aspirin or clopidogrel and aspirin by a specially trained and qualified nurse. We prepared sequentially numbered opaque sealed envelopes and 900 labels for each drug labelled Drug A or B. According to the randomization chart, put them into envelopes numbered 1 to 900. Envelopes were attached to the patient's files. Patients were recruited sequentially and were given enrolment numbers starting from 1, which were mentioned on their files. Files with the same number as the patient enrolment number were opened, and the patients were assigned to receive drugs A or B. Drug A included ticagrelor, and Drug B included clopidogrel. The statistical analysis was performed by an independent statistician who did not know the treatment protocol of groups A or B.
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •the investigators included both genders with eligible ages ranging between 18-75 years, with the first-ever presentation with acute 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 < 4 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).
- •We 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.
- •For safety measures and to avoid associated confounders, we 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.
- •We 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,
- •The investigators considered pregnant and lactating patients or those with stroke due to venous thrombosis, those with wake-up stroke and stroke following cardiac arrest or profuse hypotension ineligible for our trial.
- •The investigators excluded patients who were regular users of drugs that affect clopidogrel metabolism, such as proton pump inhibitors, statins, ketoconazole, dihydropyridine calcium channel blockers, and rifampin.
Arms & Interventions
ticagrelor arm
The ticagrelor arm will receive (180 mg loading dose during the first 12 hours of stroke onset, followed by 90 mg b.i.d from the 2nd to the 90th day)
Intervention: Ticagrelor 90 MG Oral Tablet (Drug)
clopidogrel arm
The clopidogrel arm will receive (a 300 mg loading dose during the first 12 hours of stroke onset, followed by 75 mg once daily from the 2nd day to the 90th day).
Intervention: Clopidogrel tablet (Drug)
Outcomes
Primary Outcomes
-the rate of new stroke in each group
Time Frame: 90 days
Assessed during the follow-up period through telephone calls twice per week, a face-to-face interview, and suitable brain imaging in the outpatient clinic once per month and continued for three months
Rate of drug-related hemorrhagic complications
Time Frame: 90 days
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.
Secondary Outcomes
- Value of National Institute of Health Stroke Scale (NIHSS) after one week(7 days)
- value of Modified Rankin Scale (mRS) at one week(90 days)
- value of Modified Rankin Scale(mRS) at three months(90 days)
- rate of composite recurrent stroke, myocardial infarction, and death due to vascular events(90 days)
- rate of drug adverse effects(90 days)
Investigators
Mohamed G. zeinhom, MD
principal investigator
Kafrelsheikh University