Combining Use of Clopidogrel With Atorvastatin or Rosuvastatin in Patients With Large-vessel Ischemic Stroke

Combining Use of Clopidogrel With Atorvastatin or Rosuvastatin in Patients With Large-vessel Ischemic Stroke, a Randomized Controlled Single-blinded Trial

Along with the current clinical trial, the impact of adding atorvastatin or rosuvastatin in the first 24 hours on the clinical outcomes of first-ever large-vessel ischemic stroke patients treated with clopidogrel assessed through NIHSS, mRS, and possible adverse effects.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke
• Intervention / Treatment: Drug: Atorvastatin 40 Mg Oral Tablet; Drug: Rosuvastatin 20mg; Drug: Clopidogrel 75 Mg Oral Tablet

Detailed Description

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 atorvastatin arm, which consisted of 300 patients who received 40 mg daily atorvastatin for 3 months, and the rosuvastatin arm consisted of 300 patients who received 20 mg rosuvastatin daily for 3 months, All the patients in the two groups received open-label clopidogrel at a loading dose of 300 mg and then 75 mg daily till the end of the 3 months.

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& TOE: in indicated patients ECG Monitoring: daily ECG monitoring will be performed in indicated patients. - Carotid Duplex: carotid duplex in indicated patients.

4- ESR & Lipid Profile& liver functions: All will be tested routinely for all patients.

Every patient underwent CT brain and MRI brain using stroke protocol: T1W, T2W, FLAIR, DWI, T2 Echo Gradient, CTA, or MRA (if CTA was contraindicated), from the aortic arch through the circle of Willis. Two neuroradiologists blinded to treatment reviewed C.T. and MRI source images. Cerebrovascular vessels were divided into segments: supra-clinoid internal carotid artery, first-division middle cerebral artery (M1), second-division middle cerebral artery (M2), basilar artery (B.A.), intracranial vertebral artery (V.A.). A neuroradiologist determined whether any of these vascular segments were occluded. If there was no vascular occlusion, the patient was documented as having no large vessel occlusion. If one or more vascular segments were occluded and the patient was ineligible for thrombectomy or arterial stenting, the case history and NIHSS score were reviewed; if the vascular occlusion was in the appropriate territory to account for the clinical findings, the case was judged as having a large-vessel occlusion

Primary End Point:

The primary efficacy outcome was the rate of new stroke at 90 days

• 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 the 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 acute liver injury assessed by ALT, AST test at 90 days, statin-induced myopathy assessed by CPK at 90 days and other adverse effects assessed by a follow-up questionnaire.

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: mohamed G. Zeinhom, MD; Phone Number: 2001009606828; Email: mohamed_gomaa@med.kfs.edu.eg
• Study Contact Backup: Name: sherihan R. ahmed, MD; Phone Number: 2001113432342; Email: sherihanrezk2016@gmail.com

Study Locations

• Egypt
  • Kafr ash Shaykh, Egypt, 33511
    • Recruiting
    • Kafr Elsheikh University Hospital
    • Contact: mohamed G. Zeinhom, MD; Phone Number: 2001009606828; Email: mohamed_gomaa@med.kfs.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- males and females aged 18-75 first-ever large-vessel acute ischemic stroke

Exclusion Criteria:

• the investigators excluded patients with allergies to any of the studied drugs or who suffered from clinical seizures as a part of their stroke, those with major organ failure, malignancies, or myocardial infarction during the past six weeks, and patients who administered regular antiplatelet or anticoagulant in the previous week to avoid clouding our drug safety assessment.
• investigators excluded patients with a minor stroke (National Institutes of Health Stroke Scale (NIHSS) ≤ 3) or severe stroke (NIHSS ≥ 25), patients who had spontaneous resolution of symptoms before imaging, and patients with a history of a CNS disorder (e.g., multiple sclerosis, epilepsy, meningioma).
• investigators excluded Patients were also not eligible if carotid, cerebrovascular, or coronary revascularization was planned, requiring halting study treatment within seven days after randomization.
• investigators excluded Patients who experienced a cardioembolic stroke either prior to or post-treatment were not included in our study. Cardio-embolic strokes were diagnosed when the patient exhibited potential conditions to have a cardiac source of emboli such as mechanical cardiac valves, atrial fibrillation (AF), mitral valve prolapse, aortic valve stenosis or calcification, and patent foramen ovale .
• investigators excluded patients with clinical AF based on the presence of a conventional 12-lead electrocardiography (ECG) recording that exhibited a minimum of 30 seconds of cardiac rhythm, showing the absence of identifiable recurring P waves and irregular RR intervals (when atrioventricular conduction is not impaired).
• investigators excluded patients with a source of gastrointestinal bleeding such as peptic ulcers, patients with recurrent stroke based on appropriate clinical history, examination, and/or MRI brain findings, and those who had a blood glucose level < 50 or > 400 mg/DL or Platelet count < 100,000 or international normalized ratio > 1.4 or Prothrombin time >18.
• investigators excluded patients who were regular users of drugs that affected clopidogrel metabolism, such as proton pump inhibitors, ketoconazole, dihydropyridine calcium channel blockers, and rifampin.
• investigators excluded pregnant or lactating females, patients with venous infarction, and ischemic infarction secondary to hypo-perfusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: atorvastatin; The Atorvastatin arm consisted of 300 patients who received 40 mg daily atorvastatin for 3 months, an open-label clopidogrel at a loading dose of 300 mg, and then 75 mg daily till the end of the 3 months	Drug: Atorvastatin 40 Mg Oral Tablet; The atorvastatin group consisted of 300 patients who received 40 mg daily atorvastatin for 3 months, and open-label clopidogrel at a loading dose of 300 mg and then 75 mg daily till the end of the 3 months.; Other Names: group A; Drug: Clopidogrel 75 Mg Oral Tablet; open-label clopidogrel at a loading dose of 300 mg and then 75 mg daily till the end of the 3 months.
Active Comparator: rosuvastatin; The rosuvastatin arm consisted of 300 patients who received 20 mg daily rosuvastatin for 3 months, an open-label clopidogrel at a loading dose of 300 mg, and then 75 mg daily till the end of the 3 months	Drug: Rosuvastatin 20mg; The rosuvastatin group consisted of 300 patients who received 40 mg daily rosuvastatin for 3 months, and open-label clopidogrel at a loading dose of 300 mg and then 75 mg daily till the end of the 3 months.; Other Names: group B; Drug: Clopidogrel 75 Mg Oral Tablet; open-label clopidogrel at a loading dose of 300 mg and then 75 mg daily till the end of the 3 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the rate of new stroke at 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	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rate of drug adverse effects	Drug adverse effects: all side effects related to the drugs of our study will be reported	90 days
value of Modified Rankin Scale (mRS) at one week	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.	7 days
value of Modified Rankin Scale(mRS) at three 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.	3 months
rate of composite recurrent stroke, myocardial infarction, and death due to vascular events	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.	3 months
Value of National Institute of Health Stroke Scale (NIHSS) after one week	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. Improvement will be counted only if the NIHSS score decreases by four points or more within one week of stroke onset.	7 days

Collaborators and Investigators

• Sponsor: Kafrelsheikh University
• Investigators: Study Director: Mohamed G. Zeinhom, MD, neurology department kafr el-sheikh university

Publications and helpful links

General Publications

• Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet. 2006 May 27;367(9524):1747-57. doi: 10.1016/S0140-6736(06)68770-9.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2024
• Primary Completion (Estimated): September 10, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: April 6, 2024
• First Submitted That Met QC Criteria: April 6, 2024
• First Posted (Actual): April 11, 2024

Study Record Updates

• Last Update Posted (Estimated): September 5, 2025
• Last Update Submitted That Met QC Criteria: August 30, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: stroke; clopidogrel; Egypt; atorvastatin; rosuvastatin
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Ischemic Stroke; Stroke; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Fatty Acids; Lipids; Dosage Forms; Azoles; Hydrocarbons; Amides; Pyrimidines; Hydrocarbons, Halogenated; Pyrroles; Heptanoic Acids; Sulfonamides; Sulfones; Thiophenes; Fluorobenzenes; Hydrocarbons, Fluorinated; Ticlopidine; Thienopyridines; Atorvastatin; Clopidogrel; Rosuvastatin Calcium; Tablets
• Other Study ID Numbers: 00023098816

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All the data that support the findings of this research will be available from the corresponding author M. Zeinhom upon reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes