Ticagrelol Versus Aspirin in Ischemic Stroke

• ClinicalTrials.gov Identifier: NCT03884530
• Recruitment Status: Recruiting
• First Posted: March 21, 2019
• Last Update Posted: June 10, 2019
• Sponsor: Kafrelsheikh University
• Collaborator: Ain Shams University
• Information provided by (Responsible Party): Mohamed zeinhom Gomaa, Kafrelsheikh University

Study Description

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

Condition or disease	Intervention/treatment	Phase
Acute Stroke; Ischemic Stroke	Drug: Ticagrelor (Brilique) 90; Drug: Aspirin 75mg	Phase 2; Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 152 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Patients will be divided into 2 groups. Each group will include 76 patients. The first 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). The second 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. 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).
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Ticagrelol Versus Aspirin in Ischemic Stroke
• Actual Study Start Date: May 2, 2019
• Estimated Primary Completion Date: October 1, 2020
• Estimated Study Completion Date: April 1, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. difference between National institute of health stroke scale scores on admission and after one week in each group [ Time Frame: one week ]

   National institute of health stroke scale ( NIHSS) difference between score on admission and after one week:

   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

2. Modified Rankin scale in each group [ Time Frame: 3 months ]

   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
3. Mortality in each group [ Time Frame: 3 months ]
   Timing and cause of death will be assessed

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: mohamed zeinhom M Gomaa, M.Sc.; 01009606828 ext 20; mohamedzeinhom7@gmail.com

Contact: Hala M Elkhawas, MD; 01005297952 ext 20; halaelkhawas@hotmail.com

Locations

Egypt

Neuropsychiatry department Kafrelsheikh university hospital; Recruiting

Kafr Ash Shaykh, Egypt, 33511

Contact: mohamed zeinhom M Gomaa, M.Sc. 01009606828 ext 20 mohamedzeinhom7@gmail.com

Contact: Hala M Elkhawas, MD 01005297952 ext 20 halaelkhawas@hotmail.com

Sponsors and Collaborators

Kafrelsheikh University

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

More Information

Additional Information:

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

Publications of Results:

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.

• Responsible Party: Mohamed zeinhom Gomaa, principal investigator, Kafrelsheikh University
• ClinicalTrials.gov Identifier: NCT03884530
• Other Study ID Numbers: 2388
• First Posted: March 21, 2019
• Last Update Posted: June 10, 2019
• Last Verified: June 2019

Individual Participant Data (IPD) Sharing Statement:

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

• 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

Keywords provided by Mohamed zeinhom Gomaa, Kafrelsheikh University:

ticagrelol; aspirin

Additional relevant MeSH terms:

Stroke; Cerebral Infarction; Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Brain Infarction; Brain Ischemia; Aspirin; Ticagrelor; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists