Ticagrelor Versus Clopidogrel in Ischemic Stroke

NCT05553613 | Completed Phase 3 FDA Drug

• 1 other identifier: 23988
• Study Type: interventional
• Target: 900
• 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 the first 24 hours of first-ever ischemic stroke compared to 300 mg clopidogrel were assessed through NIHSS, mRS, duration of hospital stay, and possible adverse effects.

Conditions

Ischemic Stroke

Keywords

ticagrelor; clopidogrel; ischemic stroke; egypt; kafr el-sheikh faculty of medicine

Outcome Measures

Primary Outcomes (2)

• -the rate of new stroke in each group

  Assessed during the follow-up period through telephone calls twice per week, a face-to-face interview, and suitable brain imaging in the outpatient clinic once per month and continued for three months

  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

  90 days

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

  90 days

• 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 12 hours of stroke onset, followed by 90 mg b.i.d from the 2nd to the 90th day)

Drug: Ticagrelor 90 MG Oral Tablet

clopidogrel arm

ACTIVE COMPARATOR

The clopidogrel arm will receive (a 300 mg loading dose during the first 12 hours of stroke onset, followed by 75 mg once daily from the 2nd day to the 90th day).

Drug: Clopidogrel tablet

Interventions

Ticagrelor 90 MG Oral Tablet 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 tablet 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 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:

• We 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.
• For safety measures and to avoid associated confounders, we 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.
• We 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 considered pregnant and lactating patients or those with stroke due to venous thrombosis, those with wake-up stroke 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, 6850001, Egypt

Location

Related Publications (7)

• 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

• 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

• 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 RESULT

• 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 RESULT

• Jacobson KA, Boeynaems JM. P2Y nucleotide receptors: promise of therapeutic applications. Drug Discov Today. 2010 Jul;15(13-14):570-8. doi: 10.1016/j.drudis.2010.05.011. Epub 2010 Jun 2.

  PMID: 20594935 RESULT

• Johnston SC, Amarenco P, Albers GW, Denison H, Easton JD, Held P, Jonasson J, Minematsu K, Molina CA, Wong LK. Acute Stroke or Transient Ischemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes (SOCRATES) trial: rationale and design. Int J Stroke. 2015 Dec;10(8):1304-8. doi: 10.1111/ijs.12610. Epub 2015 Aug 26.

  PMID: 26311628 RESULT

• Ahmed SR, Nahas NE, Khalil MFE, Elbassiouny A, Almoataz MA, Omar TY, Daabis AMA, Refat HM, Ebied AAMK, Hassan AM, Mohamed DMA, Ismaiel M, Zeinhom MG. TICA-CLOP STUDY: Ticagrelor Versus Clopidogrel in Acute Moderate and Moderate-to-Severe Ischemic Stroke, a Randomized Controlled Multi-Center Trial. CNS Drugs. 2025 Jan;39(1):81-93. doi: 10.1007/s40263-024-01127-7. Epub 2024 Nov 9.

  PMID: 39520630 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Ticagrelor; Tablets; 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; Dosage Forms; Pharmaceutical Preparations; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• mohamed G. Zeinhom, PHD

  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 900 labels for each drug labelled Drug A or B. According to the randomization chart, put them into envelopes numbered 1 to 900. 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: principal investigator

Model Details: We will conduct our randomized controlled trial, which will contain 2 arms; the ticagrelor arm (group A) 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), and the Clopidogrel arm will receive (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: September 19, 2022
• First Posted: September 23, 2022
• Study Start: October 1, 2022
• Primary Completion: October 1, 2023
• Study Completion: January 1, 2024
• Last Updated: May 14, 2024

Record last verified: 2024-05

Locations

EG (1)