Ticagrelor Versus Clopidogrel in Large Vessel Ischemic Stroke

NCT06120725 | Completed Phase 3 FDA Drug

• 1 other identifier: 0023988
• Study Type: interventional
• Target: 580
• Locations: 1 country
• Sites: 1

Brief Summary

Along with the current clinical trial, the efficacy and safety of 180 mg loading dose of ticagrelor administered within 24 hours of first-ever large-vessel ischemic stroke compared to 300 mg clopidogrel were assessed through NIHSS, mRS, and possible adverse effects.

Conditions

Ischemic Stroke

Keywords

ticagrelor; clopidogrel; large-vessel ischemic stroke; Egypt

Outcome Measures

Primary Outcomes (2)

• rate of new ischemic stroke

  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

• Rate of drug-related hemorrhagic complications

  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

Secondary Outcomes (5)

• Value of National Institute of Health Stroke Scale (NIHSS) after one week

  7 days

• value of Modified Rankin Scale (mRS) at one week

  7 days

• value of Modified Rankin Scale(mRS) at three months

  3 months

• rate of composite recurrent stroke, myocardial infarction, and death due to vascular events

  90 days

• rate of drug adverse effects

  90 days

Study Arms (2)

ticagrelor arm

ACTIVE COMPARATOR

The ticagrelor arm will receive (180 mg loading dose during the first 24 hours of stroke onset, followed by 90 mg b.i.d from the 2nd to the 90th day)

Drug: Ticagrelor 90 MG

clopidogrel arm

ACTIVE COMPARATOR

The clopidogrel arm will receive (a 300 mg loading dose during the first 24 hours of stroke onset followed by 75 mg once daily from the 2nd day to the 90th day)

Drug: Clopidogrel

Interventions

Ticagrelor 90 MG DRUG

Efficacy and safety of 180 mg loading dose of ticagrelor administered within 24 hours of first-ever ischemic stroke followed by 90 mg bid for 3 months will be assessed through NIHSS, mRS, duration of hospital stay, new ischemic stroke, and possible adverse effects.

Also known as: group A

ticagrelor arm

Clopidogrel DRUG

Efficacy and safety of 300 mg clopidogrel followed by 75 mg once daily for 3 months will be assessed through NIHSS, mRS, duration of hospital stay, new ischemic stroke, and possible adverse effects.

Also known as: group B

clopidogrel arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• the investigators included both genders with eligible ages ranging between 18-75 years, with the first-ever presentation with acute large-vessel ischemic stroke who received antiplatelet treatment within the first 24 hours of the onset of ischemic stroke. Patients with previous transient ischemic attacks (TIA) were not excluded from the study. Patients are not eligible for rt-PA treatment

You may not qualify if:

• the investigators excluded patients who had not been followed up on for 90 days after enrollment, those with NIHSS ≤ 3 or ≥ 25 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 proton pump inhibitors, statins, ketoconazole, dihydropyridine calcium channel blockers, and rifampin.

Sponsors & Collaborators

• Kafrelsheikh University: lead

Study Sites (1)

Kafr Elsheikh University Hospital

Kafr ash Shaykh, 33511, Egypt

Location

Related Publications (6)

• Meyer DM, Albright KC, Allison TA, Grotta JC. LOAD: a pilot study of the safety of loading of aspirin and clopidogrel in acute ischemic stroke and transient ischemic attack. J Stroke Cerebrovasc Dis. 2008 Jan-Feb;17(1):26-9. doi: 10.1016/j.jstrokecerebrovasdis.2007.09.006.

  PMID: 18190818 BACKGROUND

• Gachet C, Stierle A, Cazenave JP, Ohlmann P, Lanza F, Bouloux C, Maffrand JP. The thienopyridine PCR 4099 selectively inhibits ADP-induced platelet aggregation and fibrinogen binding without modifying the membrane glycoprotein IIb-IIIa complex in rat and in man. Biochem Pharmacol. 1990 Jul 15;40(2):229-38. doi: 10.1016/0006-2952(90)90683-c.

  PMID: 2375765 BACKGROUND

• 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 RESULT

• 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 RESULT

• 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 RESULT

• Zeinhom MG, Elbassiouny A, Mohamed AM, Ahmed SR. Ticagrelor Versus Clopidogrel in Acute Large-Vessel Ischemic Stroke: A Randomized Controlled Single-Blinded Trial. CNS Drugs. 2024 May;38(5):387-398. doi: 10.1007/s40263-024-01080-5. Epub 2024 Apr 15.

  PMID: 38619649 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Ticagrelor; Clopidogrel

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• mohamed G. Zeinhom, MD

  neurology department kafr el-sheikh university

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: An independent statistician generated a blocked randomization sequence using computer-generated random numbers; in a one-to-one ratio, participants were randomly assigned to receive either loading doses of ticagrelor and aspirin or clopidogrel and aspirin by a specially trained and qualified nurse. We prepared Sequentially numbered opaque sealed envelopes and 580 labels for each drug labeled Drug A or B. According to the randomization chart, put them into envelopes numbered 1 to 580. Envelopes were attached to the patient's files. Patients were recruited sequentially and were given enrolment numbers starting from 1, which were mentioned on their files. Files with the same number as the patient enrolment number were opened, and the patients were assigned to receive drugs A or B. Drug A included ticagrelor, and Drug B included clopidogrel. The statistical analysis was performed by an independent statistician who did not know the treatment protocol of groups A or B.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Model Details: The investigators will conduct our single-blinded randomized controlled trial, which will contain 2 arms; the ticagrelor arm will receive (a 180 mg loading dose during the first 24 hours of stroke onset, followed by 90 mg b.i.d from the 2nd to the 90th day). The Clopidogrel arm will receive (a 300 mg loading dose during the first 24 hours of stroke onset, followed by 75 mg once daily from the 2nd day to the 90th day).

Study Record Dates

• First Submitted: November 1, 2023
• First Posted: November 7, 2023
• Study Start: September 1, 2021
• Primary Completion: September 1, 2023
• Study Completion: November 1, 2023
• Last Updated: December 29, 2023

Record last verified: 2023-12

Locations

EG (1)