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

October 18, 2016 updated by: Sheba Medical Center

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 .

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Tel Hashomer, Israel, 52621
        • Leviev Heart Center, Sheba Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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.
Other Names:
  • Tedaptive

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
3 months

Secondary Outcome Measures

Outcome Measure
Time Frame
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.
3 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2010

Primary Completion (ACTUAL)

January 1, 2013

Study Completion (ACTUAL)

January 1, 2013

Study Registration Dates

First Submitted

January 16, 2010

First Submitted That Met QC Criteria

January 16, 2010

First Posted (ESTIMATE)

January 20, 2010

Study Record Updates

Last Update Posted (ESTIMATE)

October 19, 2016

Last Update Submitted That Met QC Criteria

October 18, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SHEBA-09-7418-MS-CTIL

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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