Ticagrelol Versus Aspirin in Ischemic Stroke

There is a debate whether ticagrelor is superior to aspirin in treating patients with ischemic stroke or not, most of the studies examine the effect of both drugs within 24 hours of acute stroke some find that there is no difference between ticagrelor and aspirin, others find that ticagrelor is superior to aspirin.

At this study the investigators aim at evaluating the role of loading ticagrelor received within 9 hours of acute ischemic stroke in improving neurological outcome of stroke. And evaluating the risk of hemorrhagic and non- hemorrhagic complications associated with the use of ticagrelor180 ml oral loading dose within 9 hours acute ischemic stroke

Study Overview

• Status: Completed
• Conditions: Ischemic Stroke; Acute Stroke
• Intervention / Treatment: Drug: Ticagrelor (Brilique) 90; Drug: Aspirin 75mg

Detailed Description

ticagrelor is acyclo-pentyltriazolo-pyrimidine antiplatelet drug that inhibits the P2Y12which is a subtype of adenosine diphosphate (ADP)receptor.

It is a potent , direct-acting oral agent and it is reversibly binding P2Y12 receptors antagonist unlike the irreversible agents as clopidogrel, prasugrel, ticlopidine.

In 2011, the U.S. Food and Drug Administration (FDA) approved the blood-thinning drug (ticagrelor) to treat acute coronary syndromes, and in 2015, it approved it as long-term treatment in patient with history of heart attack.

In 2018, the American Heart Association ( AHA ) and American stroke Association (ASA) Guidelines for the Early Management of Patients with Acute Ischemic Stroke stated that, ticagrelor was not found to be superior to aspirin. However, because there were no significant safety differences, ticagrelor may be a reasonable alternative in stroke patients who have a contraindication to aspirin.

Aspirin overall reduces the risk of major vascular events by 13% Moreover, the risk of hemorrhagic events limits the use of aspirin in this setting, so the investigators aim at examining the hemorrhagic risks associated with use of loading Ticagrelor 180 ml within 9 hours of 1st ever acute ischemic stroke and compare the neurological outcomes in two groups of patients with 1st ever acute ischemic stroke receiving within 9 hours either Aspirin(300 mg (4 tablets of 75 mg) as a single loading oral dose, and will then be commenced on 300 mg Aspirin daily for 2 weeks then 75 mg daily after that for 3 months and the other received 180 mg ticagrelor (2 tablets of 90 mg) as a single loading oral dose, and continue on 180 mg ticagrelor (1 tablet of 90 mg every 12 hours) for 3 months.

• Study Type: Interventional
• Enrollment (Actual): 169
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Kafr Ash Shaykh, Egypt, 33511
    • Neuropsychiatry department Kafrelsheikh university hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male & female patients will be included
2. Age between 18 - 75 years
3. First ever presentation with acute ischemic stroke.Previous transient ischemic attacks (TIA's) are not excluding
4. Ictus to drug time does not to exceed 9 hours.

Exclusion Criteria

1. Patient eligible for recombinant tissue plasminogen activator (rTPA)
2. patients with( national institute of health stroke scale (NIHSS) below 3 or above 25
3. patients with active malignancy
4. patients with major surgery in past 3 months
5. patients with known allergy to study drugs
6. patients with acute myocardial infarction in past 6 months
7. patients known to suffer from multiple sclerosis or epilepsy
8. pregnancy or lactation
9. patients with history of head trauma with residual neurological deficits
10. patients on regular ticagrelol in past week
11. patients with international normalized ratio (INR) more than 1.3 or prothrombin time (PT) more than 18
12. patients with venous thrombosis
13. patients with platelet count less than 100000 or white blood cells (WBCs) less than 3000 or hematocrit value less than 0.25
14. blood glucose less than 50 mg/DL or more than 400

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ticagrelor ( Brilique) group; the group will receive 180 mg ticagrelor (2 tablets of 90 mg) as a single loading oral dose, and continue on 180 mg ticagrelor (1 tablet of 90 mg every 12 hours) for 3 months	Drug: Ticagrelor (Brilique) 90; Drug name Brilique 90 ml Drug form tablet
Active Comparator: Aspirin Group; The group will receive 300 mg Aspirin (4 tablets of 75 mg) as a single loading oral dose, and will then be commenced on 300 mg Aspirin daily for 2 weeks then 75 mg daily after that for 3 months	Drug: Aspirin 75mg; Drug name Aspirin 75 ml Drug form tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hemorrhagic transformation of infarction within 48 hours of loading anti platelet in each group	hemorrhagic transformation detected by brain imaging CT and/or MRI brain will be done after 2 days of onset	48 hours
amount of peripheral bleeding within 48 hours of loading anti platelet in each group	amount of peripheral bleeding measured in milliliter in each group	48 hours
frequency of peripheral bleeding within 48 hours of loading anti platelet in each group	amount of peripheral bleeding measured as ( time per day )	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
difference between National institute of health stroke scale scores on admission and after one week in each group	National institute of health stroke scale ( NIHSS) difference between score on admission and after one week: we consider favorable outcome if there is decrease in NIHSS by 4 points or more this scale ranges from 0 to 42 . the higher the value the worse outcome with the following values: 1-4 Minor stroke 5-15 Moderate stroke 16-20 Moderate to severe stroke 21-42 Severe stroke	one week or discharge
Modified Rankin scale in each group	Modified Rankin Scale (MRS): assessed at the end of 3 months , the higher the value the worse the outcome , MRS has following values : 0 = No symptoms at all; 1= No significant disability despite symptoms; 2= Slight disability; 3= Moderate disability; 4= Moderately severe disability; 5= Severe disability; bedridden; 6= Dead we consider favorable mRS if it was 2 or less	after one week and after 3 months
Mortality in each group	Timing and cause of death will be assessed	3 months

Collaborators and Investigators

• Sponsor: Kafrelsheikh University
• Collaborators: Ain Shams University
• Investigators: Study Chair: Hani Mohamed M Aref, MD, neuropsychiatry department Ain shams faculty of medicine; Study Director: Hala M Elkhawas, MD, neuropsychiatry department Ain shams faculty of medicine; Study Director: Ahmed I Elbassiouny, MD, neuropsychiatry department Ain shams faculty of medicine; Study Director: Tamer M Roushdy, MD, neuropsychiatry department Ain shams faculty of medicine; Study Director: Hossam S Mohammed, MD, neuropsychiatry department Ain shams faculty of medicine; Principal Investigator: Mohamed Zeinhom M Gomaa, M.Sc., neuropsychiatry department Kafrelsheikh faculty of medicine

Publications and helpful links

General Publications

• Johnston SC, Amarenco P, Albers GW, Denison H, Easton JD, Evans SR, Held P, Jonasson J, Minematsu K, Molina CA, Wang Y, Wong KS; SOCRATES Steering Committee and Investigators. Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack. N Engl J Med. 2016 Jul 7;375(1):35-43. doi: 10.1056/NEJMoa1603060. Epub 2016 May 10.
• 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.

Helpful Links

• https://www.ncbi.nlm.nih.gov/pubmed/27160892

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Actual): September 30, 2020
• Study Completion (Actual): September 30, 2020

Study Registration Dates

• First Submitted: March 8, 2019
• First Submitted That Met QC Criteria: March 20, 2019
• First Posted (Actual): March 21, 2019

Study Record Updates

• Last Update Posted (Actual): September 2, 2021
• Last Update Submitted That Met QC Criteria: August 30, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: aspirin; ticagrelol
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Ticagrelor
• Other Study ID Numbers: 2388

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: the individual participant data for all primary and secondary outcomes measures will be made available
• IPD Sharing Time Frame: data will be available after 6 months of study completion
• IPD Sharing Access Criteria: data access requests will be reviewed by an external independent review panel , requestors will be required to sign a data access agreement
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No