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Concomitant Use of Clopidogrel With Atorvastatin or Rosuvastatin in Patients With Minor Stroke or TIA

Phase 3
Recruiting
Conditions
Ischemic Stroke
Interventions
Registration Number
NCT06358313
Lead Sponsor
Kafrelsheikh University
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 minor stroke or TIA patients treated with clopidogrel and aspirin assessed through NIHSS, mRS, and possible adverse effects.

Detailed Description

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

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 aspirin at a loading dose of 75 to 300 mg and then 75 mg daily till the end of the 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.

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.

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

• 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 & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
600
Inclusion Criteria
  • males and females aged 18-75
  • first-ever minor acute ischemic stroke (National Institutes of Health Stroke Scale score of ≤3) or high-risk TIA, which was defined by an ABCD2 score of ≥4 (the ABCD2 score is based on age, blood pressure, clinical features, duration of TIA, and the presence or absence of diabetes; range, 0-7, with higher scores indicating a higher risk of stroke Patients are not eligible for rt-PA treatment
Exclusion Criteria
  • the investigators excluded patients with NIHSS ≥ 4 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.

The investigators excluded patients who were regular users of drugs that affect clopidogrel metabolism, such as ketoconazole, dihydropyridine calcium channel blockers, and rifampin.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
atorvastatinAtorvastatin 40mgThe Atorvastatin arm consisted of 300 patients who received 40 mg daily atorvastatin for 3 months, an open-label aspirin at a loading dose of 75 to 300 mg and then 75 mg daily till the end of the 3 months, and an open-label clopidogrel at a loading dose of 300 mg and then 75 mg daily till the end of the 3 months
rosuvastatinRosuvastatin 20mgThe rosuvastatin arm consisted of 300 patients who received 20 mg daily rosuvastatin for 3 months, an open-label aspirin at a loading dose of 75 to 300 mg and then 75 mg daily till the end of the 3 months, and an open-label clopidogrel at a loading dose of 300 mg and then 75 mg daily till the end of the 3 months
Primary Outcome Measures
NameTimeMethod
the rate of new stroke at 90 days90 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.

Secondary Outcome Measures
NameTimeMethod
Value of National Institute of Health Stroke Scale (NIHSS) after one week7 days

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. The improvement will be counted only if there is a decrease in NIHSS score by four points or more within one week of stroke onset.

rate of drug adverse effects90 days

Drug adverse effects: all side effects related to the drugs of our study will be reported

value of Modified Rankin Scale(mRS) at three months3 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.

value of Modified Rankin Scale (mRS) at one week7 days

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.

rate of composite recurrent stroke, myocardial infarction, and death due to vascular events3 months

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.

Drug adverse effects: all side effects related to the drugs of our study will be reported90 days

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.

Trial Locations

Locations (1)

Kafr Elsheikh University Hospital

🇪🇬

Kafr Ash Shaykh, Egypt

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