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

Ischemic Stroke Clinical Trial

Official title:

Concomitant Use of Clopidogrel With Atorvastatin or Rosuvastatin in Patients With Minor Stroke or TIA, a Randomized Controlled Single-blinded Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06358313
• Other study ID #: 0023098816
• 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 minor stroke or TIA patients treated with clopidogrel and aspirin assessed through NIHSS, mRS, and possible adverse effects.

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 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 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.

Related Conditions & MeSH terms

• Ischemic Stroke
• Stroke

Intervention

Drug:
• Atorvastatin 40mg
The atorvastatin group 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 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, 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 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. 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.	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