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Lipid Efficacy of the Extended Release Niacin/Laropiprant Combination in Patients With Cardiovascular Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01308203
Recruitment Status : Terminated (Merck has decided to discontinue all studies with extended-release niacin/laropiprant.because the HPS2-THRIVE did not meet its primary endpoint)
First Posted : March 4, 2011
Last Update Posted : August 19, 2015
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Daniel A. Siniawski, Hospital Italiano de Buenos Aires

Tracking Information
First Submitted Date  ICMJE March 3, 2011
First Posted Date  ICMJE March 4, 2011
Last Update Posted Date August 19, 2015
Study Start Date  ICMJE October 2011
Actual Primary Completion Date January 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 3, 2011)
Nominal change from baseline in low density lipoprotein- cholesterol (LDL-C) at 12 weeks of treatment with the extended release niacin /laropiprant combination added to usual therapy. [ Time Frame: Week -1, baseline (week 0), week (12 ± 2 days) and week 24 (± 2days). ]
Will be calculated by the Friedewald equation. With plasma triglycerides levels >400 mg/dL, LDL-C will be measured by an homogeneous method.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 3, 2011)
Efficacy on other lipid variables: high density lipoprotein-cholesterol (HDL-C), triglycerides, total cholesterol (TC), TC/HDL-C ratio, apolipoprotein B (ApoB), apolipoprotein A1 (ApoA), ApoB/ApoA ratio and lipoprotein (a) [Lp(a)]. [ Time Frame: Baseline (week 0), week 12 (± 2 days) and week (24 ± 2 days). ]
TC: enzymatic method. HDL-C: homogeneous direct method. Lp(a),ApoA and ApoB: nephelometric method, using an Immage immunochemistry system (Beckman Coulter).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Lipid Efficacy of the Extended Release Niacin/Laropiprant Combination in Patients With Cardiovascular Disease
Official Title  ICMJE Lipid Efficacy and Effects on HDL-C Metabolism of the Extended Release Niacin/Laropiprant Combination Added to Usual Therapy in Patients With Cardiovascular Disease and Low HDL-C That Did Not Achieve the Optional Very Low LDL-C Goal
Brief Summary
  • Clinical studies with statins have shown that patients that suffered a cardiovascular event have a high residual risk. Residual risk decreases with the attaining of progressive lower LDL-C levels.
  • In patients treated with statins, HDL-C level is an independent inverse predictor of subsequent CV and coronary plaque progression, even when LDL-C levels are less than 70 mg/dL.
  • Therefore the purpose on this study is to assess the lipid efficacy on lipid profile and effects on HDL-C metabolism and function of the extended release niacin/laropiprant combination added to usual therapy in very high risk patients with cardiovascular disease and low HDL-C that did not achieve the optional very low LDL-C or non-HDL-C goals
Detailed Description

During the screening period, patients will be pre-selected from medical records of patients that met the inclusion criteria. Patients who fulfilled the eligibility criteria will be invited to participate in the study by signing the consent form. After consenting, a screening blood sample test will be taken to determine TC, HDL-C, TG, LDL-C, non-HDL-C (the difference between TC and HDL-C), ALT, AST, CK, hemoglobin A1c (HbA1c), uric acid and TSH in the local laboratory. Patients who have HDL-C, LDL-C and/or non-HDL-C within inclusion criteria and had none of the biochemical exclusion criteria will be randomized one week after the screening blood test. Further blood samples will be obtained at baseline, 4 weeks (± 2 days), 12 weeks (± 2 days), 16 weeks (± 2 days) and 24 weeks (± 2 days). The blood samples will be centrifuged a 2000 rpm and a tube with blood serum will be sent to the local laboratory for measuring plasma levels of TC, HDL-C, TG, LDL-C, ALT, AST, CK, fasting glucose, HbA1c, creatinine, uric acid, ApoB, ApoA, Lp(a), high sensibility-C Reactive Protein (hs-CRP) and HDL-C sub-fractions (baseline, weeks 12 and 24). ALT, AST, CK, fasting glucose, creatinine and uric acid will be measured at weeks 4 and 16. A second tube will be frozen in -70ºC refrigerator an will be sent to the Department of Clinical Biochemistry of the Faculty of Pharmacy and Biochemistry from the University of Buenos Aires (Argentina) to determine: paraoxonase 1/arylesterase activity (PON1), soluble cell adhesion molecule level (ICAM-1), tumor necrosis factor-α (TNF-α), lipoprotein-associated phospholipase A2 (Lp-PLA2) and cholesterol ester transfer protein (CETP) activity. A third tube will be frozen in -70ºC refrigerator an will be sent to the Cardiovascular Research Center of the Faculty of Medical Sciences from the University of La Plata (Argentina) to determine ex vivo cellular cholesterol efflux capacity.

A unique patient number will be provided by the randomization coordinating centre from the Hospital Italiano de Buenos Aires.

Randomized patient will received a bottle of 35 pills with 1g ERN/20mg LRPT or placebo. At week 4 (± 2 days), after randomization the patient will be assessed in the outpatient clinic. Patients with good tolerance to the study medication will receive four bottles of 35 pills with 1g ERN/20mg LRPT or placebo. At week 12 (± 2 days), patients will be assessed in the outpatient clinic patients and will be crossed over to placebo or active medication. Patients will receive a bottle of 35 pills with 1g ERN/20mg LRPT or placebo. At week 16 (± 2 days), patients with good tolerance to the study medication will receive four bottles of 35 pills with 1g ERN/20mg LRPT or placebo.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Coronary Artery Disease
  • Dyslipidemias
Intervention  ICMJE
  • Drug: Extended release niacin/laropiprant
    Randomized patient will received 1 tablet of 1g ERN/20 mg LRPT for the first 4 weeks of treatment. At week 4 (± 2 days)the patient will be assessed in the outpatient clinic. Patients with good tolerance to the study medication will receive 2 tablets of 1 g ERN/20 mg LRPT that should be taken together for the next 8 weeks. At week 12 (± 2 days), patients will be assessed in the outpatient clinic patients and will be crossed over to placebo.
  • Drug: placebo
    Randomized patient will received 1 oral 1 g tablet of placebo for the first 4 weeks of treatment. At week 4 (± 2 days), after randomization the patient will be assessed in the outpatient clinic. Patients with good tolerance to the study medication will receive 2 oral 1 g tablets of placebo that should be taken together for the next 8 weeks. At week 12 (± 2 days), patients will be assessed in the outpatient clinic patients and will be crossed over to active medication.
Study Arms  ICMJE
  • Experimental: Extended release niacin /laropiprant
    The patients will be randomized to one of two arms. The intervention is with the extended release niacin laropiprant combination, that is an add on of the usual medication that the primary care physician gave them to treat their lipid disorder (statin, ezetimibe or the combination of both).
    Intervention: Drug: Extended release niacin/laropiprant
  • Placebo Comparator: placebo
    The patients will received placebo added to the usual therapy their primary care physician gave them to treat their lipid disorder (statin, ezetimibe or the combination of both).
    Intervention: Drug: placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 3, 2011)
32
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 2013
Actual Primary Completion Date January 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Men between 21 and 75 years old.
  • Very high risk patients (according NCEP-ATP III definition) with coronary heart disease (CHD) or peripheral arterial disease (PAD), documented by an angiographic study.
  • Clinical stability.
  • Low HDL-C plasma levels: < 40 mg/dL in men or <50 mg/dL in women in the screening and lead-in blood sample tests.
  • LDL-C plasma levels between 70-100 mg/dL or non-HDL-C between 100-130 mg/dL if TG were > 200 mg/dL in the screening and lead-in blood sample tests.
  • Statin based-treatment with or without ezetimibe in a stable dose in last 8 weeks.
  • Women must be postmenopausal for at least 2 years and ≤ 75 years old.

Exclusion Criteria:

  • Coronary event o arterial revascularization in the past 6 months.
  • Uncontrolled diabetes mellitus (HbA1C > 8%).
  • Acute crisis, history of gout or uric acid > 9 mg/dL.
  • Thyroid stimulating hormone (TSH) outside the central laboratory's normal reference range.
  • Renal insufficiency (creatinine > 1.5 mg/dL).
  • Baseline alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels > 1.5 UNL.
  • Baseline creatine kinase (CK) > 2 UNL.
  • Triglycerides plasma level ≥ 500 mg/dL.
  • Active fibrate therapy.
  • Age > 75 years old.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01308203
Other Study ID Numbers  ICMJE 1608
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Daniel A. Siniawski, Hospital Italiano de Buenos Aires
Original Responsible Party Daniel A. Siniawski, Cardiology Department, Hospital Italiano de Buenos Aires
Current Study Sponsor  ICMJE Daniel A. Siniawski
Original Study Sponsor  ICMJE Hospital Italiano de Buenos Aires
Collaborators  ICMJE Merck Sharp & Dohme LLC
Investigators  ICMJE Not Provided
PRS Account Hospital Italiano de Buenos Aires
Verification Date August 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP