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

Ischemic Stroke Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06360120
• Other study ID #: 00023098816
• Status: Recruiting
• Phase: Phase 3
• Start date: April 10, 2024
• Est. completion date: May 10, 2025

Study information

• Verified date: April 2024
• Source: Kafrelsheikh University
• Contact: mohamed G. Zeinhom, MD
• Phone: 2001009606828
• Email: mohamed_gomaa[@]med.kfs.edu.eg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

After the ethics committee of the faculty of medicine at Kafr el-Sheik University approves, the investigators will conduct a randomized controlled trial between April 2024 and April 2025.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: May 10, 2025
• Est. primary completion date: April 10, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• We 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.

We 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).

Patients were also not eligible if carotid, cerebrovascular, or coronary revascularization was planned, requiring halting study treatment within seven days after randomization.

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 . The patient was diagnosed 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).

We 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.

We excluded patients who were regular users of drugs that affected clopidogrel metabolism, such as proton pump inhibitors, ketoconazole, dihydropyridine calcium channel blockers, and rifampin.

We excluded pregnant or lactating females, patients with venous infarction, and ischemic infarction secondary to hypo-perfusion.

Related Conditions & MeSH terms

• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

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.
• 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.

Locations

Country	Name	City	State
Egypt	Kafr Elsheikh University Hospital	Kafr Ash Shaykh

Sponsors (1)

Lead Sponsor	Collaborator
Kafrelsheikh University

Country where clinical trial is conducted

Egypt, 

References & Publications (3)

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. — View Citation

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-An — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	rate of drug adverse effects	Drug adverse effects: all side effects related to the drugs of our study will be reported	90 days
Secondary	Drug adverse effects: all side effects related to the drugs of our study will be reported	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.	90 days