Influence of Varenicline on the Antiplatelet Action of Clopidogrel

Coronary Artery Disease Clinical Trial

— VACL  

Official title:

Influence of Varenicline on the Antiplatelet Action of Clopidogrel : the Randomized, Open-label VACL (Varenicline Clopidogrel) Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01308671
• Other study ID #: PCTC-001-WS704502
• Status: Recruiting
• Phase: N/A
• First received: January 28, 2011
• Last updated: June 23, 2015
• Start date: October 2010
• Est. completion date: April 2016

Study information

• Verified date: April 2015
• Source: General Hospital of Chinese Armed Police Forces
• Contact: Hui Liang Liu, Doctor
• Phone: 86-10-88276531
• Email: lhl518[@]vip.sina.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate the effects of steady-state varenicline on the antiplatelet action of clopidogrel in patients with coronary artery disease.

Description:

Smoking is a major risk factor for cardiovascular disease (CVD). Compared with nonsmokers, smokers are approximately twice as likely to develop CVD, and three times more likely to die from it. This increased risk is due to the deleterious effects of smoking on endothelial function and blood coagulation, and the development of coronary atherosclerotic plaques. A research showed that continued smoking after successful percutaneous coronary intervention(PCI) is associated with an increased risk of restenosis. However, smoking cessation can make a 36% reduction in crude relative risk (RR) of mortality for patients with CVD. Hence current management guidelines now advocate smoking cessation, in addition to controlling hypertension and dyslipidemia, as part of an overall cardiovascular risk reduction strategy. Varenicline is a novel selective nicotinic acetylcholine receptor partial agonist that has been approved in over 70 countries worldwide as an aid to smoking cessation. Clopidogrel is widely used by patients with coronary artery disease undergoing PCI. The relationship between smoking and cardiovascular disease increases the prospect of patients receiving smoking cessation therapy and Clopidogrel concomitantly in clinical practice. Plasma protein binding of Varenicline is low(≤20%) and independent of age or renal function. The major route of clearance for varenicline is renal excretion. Clopidogrel, a prodrug, is metabolized by 2 consecutive cytochrome P450-dependent steps to its active metabolite, which binds irreversibly to the platelet P2Y12 receptor. The likelihood of a clinically relevant drug-drug interaction between varenicline and Clopidogrel was considered to be low; nevertheless, the possibility of an interaction between these 2 drugs is lack of clinical evidences. Hence, our hypothesis is that varenicline may have no influence on the antiplatelet action of clopidogrel.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 198
• Est. completion date: April 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 79 Years

Eligibility

Inclusion Criteria:

• patients with coronary artery disease(CAD) undergoing PCI in hospital

• smoke 10 or more cigarettes per day

• fewer than 3 months of smoking abstinence in the past year

• motivation to stop smoking

Exclusion Criteria:

• history of previous treatment with clopidogrel or varenicline

• thrombocytopenia(<150,000 platelets/ml)

• bleeding disorder

• liver disease

• gastrointestinal ulcer

• pregnancy

• cancer

• clinically significant allergic reactions

• mental disorders

• drug or alcohol abuse

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Varenicline
Varenicline will be administrated 0.5 mg Qd for 3 days,0.5 mg Bid for 4 days, and then 1 mg Bid for 14 days

Behavioral:
• Counseling and psychosocial support
Blank group will receive the same counseling and psychosocial support as varenicline group

Locations

Country	Name	City	State
China	General Hospital of Chinese People's Armed Police Forces	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
General Hospital of Chinese Armed Police Forces

Country where clinical trial is conducted

China, 

References & Publications (11)

Aleil B, Ravanat C, Cazenave JP, Rochoux G, Heitz A, Gachet C. Flow cytometric analysis of intraplatelet VASP phosphorylation for the detection of clopidogrel resistance in patients with ischemic cardiovascular diseases. J Thromb Haemost. 2005 Jan;3(1):85 — View Citation

Bliden KP, Dichiara J, Lawal L, Singla A, Antonino MJ, Baker BA, Bailey WL, Tantry US, Gurbel PA. The association of cigarette smoking with enhanced platelet inhibition by clopidogrel. J Am Coll Cardiol. 2008 Aug 12;52(7):531-3. doi: 10.1016/j.jacc.2008.0 — View Citation

Burstein AH, Clark DJ, O'Gorman M, Willavize SA, Brayman TG, Grover GS, Walsky RL, Obach RS, Faessel HM. Lack of pharmacokinetic and pharmacodynamic interactions between a smoking cessation therapy, varenicline, and warfarin: an in vivo and in vitro study — View Citation

Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High — View Citation

Critchley JA, Capewell S. Mortality risk reduction associated with smoking cessation in patients with coronary heart disease: a systematic review. JAMA. 2003 Jul 2;290(1):86-97. Review. — View Citation

Galan KM, Deligonul U, Kern MJ, Chaitman BR, Vandormael MG. Increased frequency of restenosis in patients continuing to smoke cigarettes after percutaneous transluminal coronary angioplasty. Am J Cardiol. 1988 Feb 1;61(4):260-3. — View Citation

McGill HC Jr, McMahan CA, Malcom GT, Oalmann MC, Strong JP. Effects of serum lipoproteins and smoking on atherosclerosis in young men and women. The PDAY Research Group. Pathobiological Determinants of Atherosclerosis in Youth. Arterioscler Thromb Vasc Bi — View Citation

Obach RS, Reed-Hagen AE, Krueger SS, Obach BJ, O'Connell TN, Zandi KS, Miller S, Coe JW. Metabolism and disposition of varenicline, a selective alpha4beta2 acetylcholine receptor partial agonist, in vivo and in vitro. Drug Metab Dispos. 2006 Jan;34(1):121 — View Citation

Puranik R, Celermajer DS. Smoking and endothelial function. Prog Cardiovasc Dis. 2003 May-Jun;45(6):443-58. Review. — View Citation

Schwarz UR, Geiger J, Walter U, Eigenthaler M. Flow cytometry analysis of intracellular VASP phosphorylation for the assessment of activating and inhibitory signal transduction pathways in human platelets--definition and detection of ticlopidine/clopidogr — View Citation

Sojka JE, Weiss JS, Samuels ML, You GM. Effect of the somatostatin analogue octreotide on gastric fluid pH in ponies. Am J Vet Res. 1992 Oct;53(10):1818-21. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The platelet reactivity index (PRI) values in the two groups	To compare PRI values at the 14-day-treatment period between the 2 groups.	14 days	Yes
Secondary	Platelet aggregometry values in the two groups	To compare platelet aggregometry values at the 7-day,14-day-treatment period between the 2 groups.	7days,14 days	Yes
Secondary	Urea nitrogen (BUN) and creatinine(Cr)values in the two groups	To compare BUN and Cr values at the 7-day,14-day-treatment period between the 2 groups.	7days, 14 days	Yes
Secondary	Number of patients with adverse events and serious adverse events as a measure of safety in the two groups	To compare the number of patients with adverse events and serious adverse events at the 7-day,14-day-treatment period between the 2 groups	7 days,14 days	Yes