Concomitant Use of Clopidogrel With Atorvastatin or Rosuvastatin in Patients With Small Vessel Stroke

Официальное название

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

Обзор

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 small vessel stroke patients treated with clopidogrel and aspirin assessed through NIHSS, mRS, and possible adverse effects.

Подробное описание

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 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.

Вмешательства

• Препарат Atorvastatin 40mg
  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.
• Препарат 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.

Первичные конечные точки

• the rate of new stroke at 90 days [Срок оценки: 90 days]

Вторичные конечные точки (6)

• Value of National Institute of Health Stroke Scale (NIHSS) after one week [Срок оценки: 7 days]
• value of Modified Rankin Scale (mRS) at one week [Срок оценки: 7 days]
• value of Modified Rankin Scale(mRS) at three months [Срок оценки: 3 months]
• rate of composite recurrent stroke, myocardial infarction, and death due to vascular events [Срок оценки: 3 months]
• rate of drug adverse effects [Срок оценки: 90 days]
• Drug adverse effects: all side effects related to the drugs of our study will be reported [Срок оценки: 90 days]

Критерии участия

Критерии включения

• males and females aged 18-75
• first-ever moderate and small vessel Stroke
• Patients are not eligible for rt-PA treatment

Критерии исключения

• The investigators excluded patients 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Египет · 1 центр

• Kafr Elsheikh University Hospital — Kafr ash Shaykh

Публикации

• 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. PMID 16731270
• 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. PMID 34515113
• 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. PMID 31867054

Идентификаторы

NCT: NCT06358313 · 0023098816

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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