The Impact of Tredaptive on Flow-Mediated Dilation in Cardiac Patients

Coronary Artery Disease Clinical Trial

Official title:

The Impact of Tredaptive (ER Niacin/Laropiprant) Compared to Placebo on Brachial Artery Endothelial Function in Patients With Stable Coronary Artery Disease on Statin Therapy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01052311
• Other study ID #: SHEBA-09-7418-MS-CTIL
• Status: Terminated
• Phase: Phase 4
• First received: January 16, 2010
• Last updated: October 18, 2016
• Start date: July 2010
• Est. completion date: January 2013

Study information

• Verified date: October 2016
• Source: Sheba Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Israeli Health Ministry Pharmaceutical Administration
• Study type: Interventional

Clinical Trial Summary

Laropiprant (LRP; Merck & Co., Inc, Whitehouse Station, NJ, USA) is a potent, once-daily, highly selective PGD2-receptor (DP1) antagonist. A combination tablet containing 1 g of extended-release niacin and 20 mg of laropiprant (ERN/LRPT) offers improved tolerability, supporting a simplified 1-2 g dosing paradigm and improved adherence. Statins and niacin improve endothelial function in cardiac patients, however, there is no data yet regarding the additive effects of raising HDL-C by ERN/LRPT and statins on endothelial function in cardiac patients. Thus the aim of the present study is to evaluate the impact of 3 months' administration of ERN/LRPT compared to placebo added to statins on endothelial function, assessed by brachial artery vasoreactivity in stable cardiac patients.

Description:

Endothelial dysfunction reflects a vascular phenotype prone to atherogenesis and may therefore serve as a marker of an inherent atherosclerotic risk. In line with this hypothesis, dysfunction of either the coronary or peripheral vascular endothelium was shown to constitute an independent predictor of cardiovascular events, providing valuable prognostic information additional to that derived from conventional risk factor assessment. Interventions, such as risk factor modification and treatment with various drugs, including statins and niacin, may improve endothelial function leading potentially to improve prognosis.

Research over the past years has identified numerous beneficial effects of high-density lipoprotein (HDL) beyond this property. These include, but not limited to, improvement of endothelial function, anti-inflammatory, anti-thrombotic, antioxidative effects and the stimulation of endothelial regeneration. Consequently, therapeutic elevation of HDL is among the primary goals of treatment of patients with coronary artery disease (CAD). Laropiprant (LRP; Merck & Co., Inc, Whitehouse Station, NJ, USA) is a potent, once-daily, highly selective PGD2-receptor (DP1) antagonist. A combination tablet containing 1 g of extended-release niacin and 20 mg of laropiprant (ERN/LRPT) offers improved tolerability, supporting a simplified 1-2 g dosing paradigm and improved adherence. Statins and niacin improve endothelial function in CAD patients, however, there is no data yet regarding the additive effects of raising HDL-C by ERN/LRPT and statins on endothelial function in CAD patients. Thus the aim of the present study is to evaluate the impact of 3 months' administration of ERN/LRPT compared to placebo added to statins on endothelial function, assessed by brachial artery vasoreactivity, and platelet function in stable CAD patients .

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion criteria:

1. Male or female = 18 years; signed informed consent

2. Outpatient CAD patients on statin therapy.

3. HDL-C < 40 mg/dL in males and < 50 mg/dL in females.

4. Left ventricular (LV) systolic dysfunction = 40% measured within the past 6 months.

5. No changes in cardiac medications during 2 weeks prior to enrollment.

Exclusion criteria:

1. Presence of transplanted tissue or organ or LVAD

2. AICD or CRT or CRTD patients.

3. Acute MI, CABG, PCI within past 3 months.

4. Congestive heart failure (CHF) = NYHA 2.

5. Ejection fraction < 40% measured within the past 6 months.

6. Malignancy.

7. Active myocarditis, or cardiomyopathy.

8. HIV infection or immunodeficiency state.

9. Chronic viral infection.

10. Acute systemic infection requiring antibiotics.

11. Chronic diarrhea or malabsorption.

12. Statin therapy initiation = 3 months.

13. Diabetes mellitus type 1.

14. Diabetes mellitus type 2 with HbA1C > 7%

15. Low-density lipoprotein cholesterol (LDL-C) > 100 mg/dL.

16. Not on statin therapy.

17. Liver function tests (LFT) = x 3 upper limit of normal (ULN) or creatinine kinase (CPK) = x 10 ULN.

18. Hypo/hyper thyroidism.

19. Liver dysfunction.

20. Renal failure with serum creatinine = 2 mg/dL.

21. Alcohol or drug abuse.

22. Refuse to sign informed consent.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Dyslipidemia
• Dyslipidemias
• Myocardial Ischemia

Intervention

Drug:
• Tredaptive (1 g extended release niacin+ 20 mg laropiprant)
Laropiprant (LRP; Merck & Co., Inc, Whitehouse Station, NJ, USA) is a potent, once-daily, highly selective PGD2-receptor (DP1) antagonist. A combination tablet containing 1 g of extended-release niacin and 20 mg of laropiprant (ERN/LRPT) once daily for the first 30 days. from day 31 to 90 it will be 2 g of extended-release niacin and 20 mg laropiprant once daily.
• Placebo
Placebo tablets once daily
• Tredaptive
Tredaptive 1 g [Laropiprant 20 mg(LRP; Merck & Co., Inc, Whitehouse Station, NJ, USA) and 1 g of extended-release niacin]from day 1 to 30 once daily. From day 31 to 90, the same but 2 g instead of 1 g of extended-release niacin.

Locations

Country	Name	City	State
Israel	Leviev Heart Center, Sheba Medical Center	Tel Hashomer

Sponsors (1)

Lead Sponsor	Collaborator
Sheba Medical Center

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the impact of 3 months' administration of ERN/LRPT compared to placebo added to statins on endothelial function, assessed by brachial artery vasoreactivity in stable CAD patients.		3 months	No
Secondary	To evaluate the impact of 3 months' administration of ERN/LRPT compared to placebo added to statins on platelet function in stable CAD patients.		3 months.	No

External Links

•   The Clinical Research Unit and Leviev Heart Center