Clinical trial NCT06360120: Combining Use of Clopidogrel With Atorvastatin or Rosuvastatin in Patients With Large-vessel Ischemic Stroke
Official title: Combining Use of Clopidogrel With Atorvastatin or Rosuvastatin in Patients With Large-vessel Ischemic Stroke, a Randomized Controlled Single-blinded Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Ischemic Stroke
Keywords: atorvastatin
rosuvastatin
clopidogrel
stroke
Egypt
Lead sponsor: Kafrelsheikh University
Sponsor class: OTHER
First posted: 2024-04-11
Enrollment: 600
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: 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
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: the rate of new stroke at 90 days
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: 7 days
measure: value of Modified Rankin Scale(mRS) at three months
timeFrame: 3 months
measure: rate of composite recurrent stroke, myocardial infarction, and death due to vascular events
timeFrame: 3 months
measure: rate of drug adverse effects
timeFrame: 90 days
measure: Drug adverse effects: all side effects related to the drugs of our study will be reported
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, MD
role: STUDY_DIRECTOR
References:
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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.
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-Analysis. Cardiovasc Ther. 2019 Dec 1;2019:1607181. doi: 10.1155/2019/1607181. eCollection 2019.