Half-dose Ticagrelor Overcomes High-dose Clopidogrel in Acute Coronary Syndrome Patients With High On-Clopidogrel Platelet Reactivity

NCT03062462 | Unknown Phase 2 FDA Drug

• 1 other identifier: SCAD-20170220
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

With the widespread use of clopidogrel, resistance to clopidogrel has been attracting increasing attention, and emerged as a new challenge adversely affecting patients clinical risk and outcome. Clopidogrel resistance means that blood platelets show little or no response to clopidogrel. It is closely associated with increased risk of serious cardiovascular events, seriously affects the prognosis of patients, and brings difficulties to clinical treatment. Guideline recommendations on the use of dual antiplatelet therapy have been formulated that ticagrelor 90 mg twice daily plus aspirin in preference to clopidogrel 75mg daily plus aspirin for ACS patients. Recent study found that ticagrelor 90mg twice a day orally could significantly reduce the occurrence of clopidogrel resistance and adverse cardiovascular events. The previous studies have reported that half-dose ticagrelor had the similar inhibitory effect on platelet aggregation as the standard-dose ticagrelor, which was significantly stronger than that in the clopidogrel group. But it is still not very clear that the effect of low-dose ticagrelor on platelet function in patients with clopidogrel resistance and coronary heart disease. Therefore, we performed this randomized, single-blind clinical trial to observe the effects of low-dose ticagrelor and double standard-dose clopidogrel on platelet aggregation and prognosis in clopidogrel resistance's patients with coronary heart disease.

Conditions

Coronary Artery Disease; Clopidogrel, Poor Metabolism of

Outcome Measures

Primary Outcomes (1)

• The platelet aggregation rate

  Light transmission aggregometry method

  up to 7 days

Secondary Outcomes (2)

• Side effects including bleeding,dyspnea and arrhythmia

  up to 7 days, 1 month, 3 months, 6 months and 12 months

• Adverse events including myocardial infarction, death, stroke, re-hospitalization for cardiovascular diseases and ischemia events

  up to 7 days, 1 month, 3 months, 6 months and 12 months

Study Arms (2)

clopidogrel

ACTIVE COMPARATOR

To observe double standard-dose clopidogrel on platelet aggregation in clopidogrel resistance's patients with coronary heart disease

Drug: Clopidogrel

ticagrelor

EXPERIMENTAL

To observe low-dose of ticagrelor on platelet aggregation in clopidogrel resistance's patients with coronary heart disease

Drug: ticagrelor

Interventions

Clopidogrel DRUG

double standard-dose clopidogrel treatment (300 mg loading dose, then 75 mg twice daily) for 5-7 days

clopidogrel

ticagrelor DRUG

half-dose ticagrelor treatment (90 mg loading dose, then 45 mg twice daily) for 5-7 days

ticagrelor

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with oral clopidogrel treatment admitted to hospital within 24 hours or long-term follow-up outpatients with oral clopidogrel treatment;
• The platelet aggregation rate (PAgR) measured with light transmission aggregometry (LTA) is decreased no more than 10% from baseline level, or PAgR is more than 46% and the percentage of inhibition of ADP-induced platelet aggregation measured by thrombelastogram is not more than 30%;

You may not qualify if:

• Planned use of glycoprotein IIb/IIIa receptor inhibitors, adenosine diphosphate (ADP) receptor antagonists, or anticoagulant therapy during the study period;
• Platelet count \<100g/L;
• Creatinine clearance rate \< 30ml/min;
• Diagnosed as respiratory or circulatory instability (cardiac shock, severe congestive heart failure NYHA II-IV or left ventricular ejection fraction \< 40%);
• A history of bleeding tendency;
• Aspirin, ticagrelor or clopidogrel allergies;
• Severe liver injury.

Sponsors & Collaborators

• First Affiliated Hospital of Harbin Medical University: lead

Study Sites (1)

whole blood lumi-aggregometer type 560 VS

Havertown, Pennsylvania, 19083, United States

RECRUITING

Related Publications (1)

• Liu GZ, Zhang S, Sun DH, Shi J, Bo WL, Wang WN, Zhang CY, Wang ZH, Feng W, He MJ, Liu YY, Li S, Zheng LQ, Li Y. Half-dose ticagrelor versus high-dose clopidogrel in reducing platelet reactivity in acute coronary syndrome patients with high on-clopidogrel platelet reactivity (divide study). Eur J Clin Pharmacol. 2019 Aug;75(8):1059-1068. doi: 10.1007/s00228-019-02687-0. Epub 2019 May 12.

  PMID: 31081522 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Clopidogrel; Ticagrelor

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Adenosine; Purine Nucleosides; Purines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Central Study Contacts

Guangzhong Liu, PhD

CONTACT

86-451-85555672; lgz2700@126.com

Yue Li, PhD

CONTACT

86-451-85555673; ly99ly@vip.163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2017
• First Posted: February 23, 2017
• Study Start: February 10, 2017
• Primary Completion: July 31, 2019
• Study Completion: December 31, 2019
• Last Updated: May 7, 2018

Record last verified: 2018-02

Locations

US (1)