Clinical trial NCT05553613: Ticagrelor Versus Clopidogrel in Ischemic Stroke
Official title: Ticagrelor Versus Clopidogrel in Ischemic Stroke. a Randomized Double-blinded Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ischemic Stroke
Keywords: ticagrelor
clopidogrel
ischemic stroke
egypt
kafr el-sheikh faculty of medicine
Lead sponsor: Kafrelsheikh University
Sponsor class: OTHER
First posted: 2022-09-23
Enrollment: 900
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: We will conduct our randomized controlled trial, which will contain 2 arms; the ticagrelor arm (group A) 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).
Primary purpose: TREATMENT

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:

* 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:

  1. Echocardiography\& TOE: in indicated patients
  2. 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

  1. Non-contrast CT brain on admission
  2. 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).
  3. 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 ischemic 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) (21) at the seventh day or discharge compared to baseline, the rates of a favourable outcome with (mRS = 0-2) (19,20) after one week and after 90 days in a face-to-face interview in the outpatient clinic, rates of 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.

Eligibility criteria: 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 \< 100,000.

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.

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Primary outcomes:
measure: -the rate of new stroke in each group
timeFrame: 90 days
measure: Rate of drug-related hemorrhagic complications
timeFrame: 90 days
Secondary outcomes:
measure: Value of National Institute of Health Stroke Scale (NIHSS) after one week
timeFrame: 7 days
measure: value of Modified Rankin Scale (mRS) at one week
timeFrame: 90 days
measure: value of Modified Rankin Scale(mRS) at three months
timeFrame: 90 days
measure: rate of composite recurrent stroke, myocardial infarction, and death due to vascular events
timeFrame: 90 days
measure: rate of drug adverse effects
timeFrame: 90 days
Other outcomes:
Locations:
city: Kafr Ash Shaykh
country: Egypt
facility: Kafr Elsheikh University Hospital
Study officials:
affiliation: neurology department kafr el-sheikh university
name: mohamed G. Zeinhom, PHD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Johnston SC, Amarenco P, Albers GW, Denison H, Easton JD, Held P, Jonasson J, Minematsu K, Molina CA, Wong LK. Acute Stroke or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial: rationale and design. Int J Stroke. 2015 Dec;10(8):1304-8. doi: 10.1111/ijs.12610. Epub 2015 Aug 26.