Along with the current clinical trial, the efficacy and safety of a 300 mg loading dose of clopidogrel administered within 24 hours of the first-ever moderate to severe ischemic stroke compared to 200 mg cilostazol were assessed through NIHSS, mRS, and possible adverse effects.

The investigators conducted a single-blinded randomized controlled trial after approval of the ethics 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 clopidogrel arm, which consisted of 435 patients who received a 300 mg loading dose followed by 75 mg once daily from the 2nd to the 90th day), and the cilostazol arm, consisting of 435 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 90 days in a face-to-face interview in the outpatient clinic, rate of recurrent ischemic stroke, rate 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

Inclusion Criteria:

• the investigators included both genders with eligible ages ranging between 18-75 years, with the first-ever presentation with moderate-to-severe 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).

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.

Patients with contraindications to the study drugs were excluded.

All the data that support the findings of this research will be available from the corresponding author M. Zeinhom upon reasonable request.

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 clopidogrel or cilostazol by a specially trained and qualified nurse. We prepared Sequentially numbered opaque sealed envelopes and 870 labels for each drug labeled Drug A or B. According to the randomization chart, put them into envelopes numbered 1 to 870. 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 clopidogrel, and Drug B included cilostazol. The statistical analysis was performed by an independent statistician who did not know the treatment protocol of groups A or B.