Clinical trial NCT03884530: Ticagrelol Versus Aspirin in Ischemic Stroke
Official title: Ticagrelol Versus Aspirin in Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Stroke
Ischemic Stroke
Keywords: ticagrelol
aspirin
Lead sponsor: Kafrelsheikh University
Sponsor class: OTHER
Collaborators: name: Ain Shams University
First posted: 2019-03-21
Enrollment: 169
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be divided into 2 groups. The first group formed of 85 patients 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). The second group formed of 84 patients 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. If the patients showed complications of the loading dose of ticagrelor (central or peripheral bleeding the dose will be minimized to 90 mg (1 tablet of 90 mg).
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: hemorrhagic transformation of infarction within 48 hours of loading anti platelet in each group
timeFrame: 48 hours
measure: amount of peripheral bleeding within 48 hours of loading anti platelet in each group
timeFrame: 48 hours
measure: frequency of peripheral bleeding within 48 hours of loading anti platelet in each group
timeFrame: 48 hours
Secondary outcomes:
measure: difference between National institute of health stroke scale scores on admission and after one week in each group
timeFrame: one week or discharge
measure: Modified Rankin scale in each group
timeFrame: after one week and after 3 months
measure: Mortality in each group
timeFrame: 3 months
Other outcomes:
Locations:
city: Kafr Ash Shaykh
country: Egypt
facility: Neuropsychiatry department Kafrelsheikh university hospital
Study officials:
affiliation: neuropsychiatry department Ain shams faculty of medicine
name: Hani Mohamed M Aref, MD
role: STUDY_CHAIR
affiliation: neuropsychiatry department Ain shams faculty of medicine
name: Hala M Elkhawas, MD
role: STUDY_DIRECTOR
affiliation: neuropsychiatry department Ain shams faculty of medicine
name: Ahmed I Elbassiouny, MD
role: STUDY_DIRECTOR
affiliation: neuropsychiatry department Ain shams faculty of medicine
name: Tamer M Roushdy, MD
role: STUDY_DIRECTOR
affiliation: neuropsychiatry department Ain shams faculty of medicine
name: Hossam S Mohammed, MD
role: STUDY_DIRECTOR
affiliation: neuropsychiatry department Kafrelsheikh faculty of medicine
name: Mohamed Zeinhom M Gomaa, M.Sc.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.