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

This study has been terminated.
(In January, 2013 Merck had decided to take steps to suspend the availability of TREDAPTIVE globally)
Sponsor:
Information provided by (Responsible Party):
Sheba Medical Center
ClinicalTrials.gov Identifier:
NCT01052311
First received: January 16, 2010
Last updated: April 21, 2013
Last verified: April 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Coronary Artery Disease
Dyslipidemia
 Drug: Tredaptive (1 g extended release niacin+ 20 mg laropiprant)
Drug: Placebo
Drug: Tredaptive
 Phase 4

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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Sheba Medical Center:

Primary Outcome Measures:
  • 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. [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the impact of 3 months' administration of ERN/LRPT compared to placebo added to statins on platelet function in stable CAD patients. [ Time Frame: 3 months. ] [ Designated as safety issue: No ]

Enrollment: 8
Study Start Date: July 2010
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo pills once daily
 Drug: Placebo
Placebo tablets once daily
Active Comparator: Active treatment
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) = tredaptive once daily from day 1 to 30. From day 31 to day 90 2 g of extended-release niacin and 20 mg of laropiprant once daily.
 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.
Other Name: Active treatment
Drug: 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.

Detailed 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 .

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01052311

Locations
Israel
Leviev Heart Center, Sheba Medical Center
Tel Hashomer, Israel, 52621
Sponsors and Collaborators
Sheba Medical Center
Investigators
Principal Investigator: Michael Shechter, MD, MA Leviev Heart Center, Sheba Medical Center
Study Director: Shlomi Matetzky, MD Leviev Heart Center, Sheba Medical Center
  More Information

Additional Information:
The Clinical Research Unit and Leviev Heart Center  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Sheba Medical Center
ClinicalTrials.gov Identifier: NCT01052311     History of Changes
Other Study ID Numbers: SHEBA-09-7418-MS-CTIL
Study First Received: January 16, 2010
Last Updated: April 21, 2013
Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration

Keywords provided by Sheba Medical Center:
Coronary artery disease
Endothelial function
Platelet function
Statins
Niacin

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Dyslipidemias
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Lipid Metabolism Disorders
Metabolic Diseases
Niacin
Nicotinic Acids
Niacinamide
 Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 16, 2013