Study in Diabetes Mellitus Patients Without Prior Myocardial Infarction or Stroke Undergoing Elective Percutaneous Coronary Intervention.

• Status: Withdrawn
• Trial end date: 2022-03-31
• Target enrollment: 0
• Participant gender: All

Summary

This study is designed to test the hypothesis that ticagrelor is superior to clopidogrel, in improving coronary microvascular function, as measured by coronary flow reserve (CFR) in patients with T2DM at high risk of cardiovascular (CV) events undergoing elective PCI.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Region Skane
• Collaborators: AstraZeneca; Hippocrates Research; IHF GmbH - Institut für Herzinfarktforschung; IRW consulting AB
• Treatments: Clopidogrel; Ticagrelor

Criteria

Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures

2. Men or women ≥18 years of age

3. Diagnosed with T2DM defined as treatment with ongoing glucose lowering drug (oral medications and/or insulin) for at least 1 month

4. Presence of CAD undergoing elective PCI

5. Impaired coronary microvascular function post PCI as defined by a CFR ≤2.5 (as per local reading)

6. TIMI 3 flow post PCI

Exclusion Criteria:

1. Previous MI defined as a documented hospitalization with a final diagnosis of spontaneous MI (with the exception of definite secondary MI [e.g., due to coronary revascularization procedure, profound hypotension, hypertensive emergency, tachycardia, or profound anemia]).

2. Previous stroke (transient ischemic attack [TIA] is not included in the stroke definition)

3. Use of an intravenous antiplatelet therapy (i.e., cangrelor or GPI) during PCI

4. On treatment with clopidogrel, prasugrel, or ticagrelor due to a prior acute major CV event (MI or stroke) (on treatment with clopidogrel due to prior vascular intervention not secondary to a major CV event is allowed)

5. Planned use of aspirin treatment at doses >150 mg od

6. Anticipated concomitant oral or intravenous therapy with strong cytochrome P450 3A4 (CYP3A4) inhibitors or CYP3A4 substrates with narrow therapeutic indices that cannot be stopped for the course of the study:

1. Strong CYP3A4 inhibitors: ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin (but not erythromycin or azithromycin), nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir

2. CYP3A4 substrates with narrow therapeutic index: quinidine, simvastatin at doses >40 mg daily or lovastatin at doses >40 mg daily

7. Hypersensitivity to ticagrelor or any of its excipients

8. Need for chronic oral anticoagulant therapy or chronic low-molecular-weight heparin

9. Patients with known bleeding diathesis or coagulation disorder

10. History of intracerebral bleed at any time, gastrointestinal (GI) bleed within the past 6 months prior to randomization, or major surgery within 30 days prior to randomization

11. Increased risk of bradycardic events (e.g., known sick sinus syndrome, second or third-degree AV block or previous documented syncope suspected to be due to bradycardia) unless treated with a pacemaker

12. Known severe liver disease (e.g., ascites and/or clinical signs of coagulopathy)

13. Renal failure requiring dialysis

14. Known platelet count <145 x109 platelets/L

15. Known hemoglobin <9 g/dL

16. Women of child-bearing potential (WOCBP)*, who are not willing to use a method of contraception that is considered highly reliable** per CTFG (Clinical Trial Facilitation Group), OR who have a positive pregnancy test at enrolment or randomization OR women who are breast-feeding

17. Inability of the patient to understand and/or comply with study procedures and/or follow up, in the opinion of the investigator, OR any conditions that, in the opinion of the investigator, may render the patient unable to complete the study

18. Life expectancy of less than 6 month based on investigator's judgement

19. Participation in another clinical study with an investigational (defined as non-approved) product, if taken within five half-lives or 28 days prior to the first administration of the trial medication, whichever is longer

20. Previous randomization in the present study

21. Severe asthma

22. Hypersensitivity to adenosine or mannitol

23. Long QT syndrome

24. Chronic obstructive lung disease, with evidence of bronchospasm

25. Severe low blood pressure

26. Unstable angina pectoris

27. Severe heart failure

28. Hypovolemia

29. Treatment with dipyradimol

30. Increased intracranial pressure * fertile, following menarche until becoming post-menopausal, unless permanently sterile (permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy) ** estrogen/progestogen or progestogen (oral, intravaginal or transdermal administration); intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomised partner; sexual abstinence