Coronary Artery DiseasePhase 4NCT01308203
Lipid Efficacy of the Extended Release Niacin/Laropiprant Combination in Patients With Cardiovascular Disease
A Phase 4 study testing Extended release niacin/laropiprant in people with Coronary Artery Disease and Dyslipidemias, run by Daniel A. Siniawski at 1 site in Argentina.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 75 years
- Conditions the study is for
- Coronary Artery Disease, Dyslipidemias
- What is being tested?
- Extended release niacin/laropiprant
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteArgentina
- Study dates
- Oct 2011to Jan 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- Baseline creatine kinase (CK) > 2 UNL.
- Triglycerides plasma level ≥ 500 mg/dL.
- Active fibrate therapy.
- Age > 75 years old.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
- 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
Read the 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.
- Conditions
- Coronary Artery Disease, Dyslipidemias
- Being tested
- Extended release niacin/laropiprant, placebo
- Medical subject headings
- Coronary Artery Disease, Dyslipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Extended release niacin/laropiprantDrug
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.
placeboDrug
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 group | Role | What they receive |
|---|---|---|
| Extended release niacin /laropiprant | Experimental | 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). Receives: Drug: Extended release niacin/laropiprant |
| placebo | Placebo comparator | 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). Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Will be calculated by the Friedewald equation. With plasma triglycerides levels >400 mg/dL, LDL-C will be measured by an homogeneous method.
Measured: Week -1, baseline (week 0), week (12 ± 2 days) and week 24 (± 2days).
Secondary outcomes (1)
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)].
TC: enzymatic method. HDL-C: homogeneous direct method. Lp(a),ApoA and ApoB: nephelometric method, using an Immage immunochemistry system (Beckman Coulter).
Measured: Baseline (week 0), week 12 (± 2 days) and week (24 ± 2 days).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2011 (estimated)
- Study startOct 2011
- Primary completionJan 2013
- Study completionJan 2013
Why it stopped: Merck has decided to discontinue all studies with extended-release niacin/laropiprant.because the HPS2-THRIVE did not meet its primary endpoint
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daniel A. Siniawski
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor-investigator, Daniel A. Siniawski, Hospital Italiano de Buenos Aires
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01308203
- Sponsor's protocol ID
- 1608
- Status last verified
- Sep 2023
- First submitted
- 3 Mar 2011
- Last updated
- 21 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01308203
- Acronym / sponsor ID
- 1608
- Conditions
- Coronary Artery Disease, Dyslipidemias
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Merck has decided to discontinue all studies with extended-release niacin/laropiprant.because the HPS2-THRIVE did not meet its primary endpoint
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Daniel A. SiniawskiUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Oct 2011
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 4 Mar 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Extended release niacin /laropiprant | Experimental | Drug: Extended release niacin/laropiprantThe 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). |
| placebo | Placebo comparator | Drug: placeboThe 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). |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (10 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Extended release niacin/laropiprantRandomized 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 | Extended release niacin /laropiprant |
| placeboRandomized 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. | Drug | placebo |
Primary outcome
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.
1 secondary outcome
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).
Results and safety
The study was stopped early (reason given: Merck has decided to discontinue all studies with extended-release niacin/laropiprant.because the HPS2-THRIVE did not meet its primary endpoint). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Extended release niacin/laropiprant in people with Coronary Artery Disease and Dyslipidemias, run by Daniel A. Siniawski at 1 site in Argentina.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Argentina. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Merck has decided to discontinue all studies with extended-release niacin/laropiprant.because the HPS2-THRIVE did not meet its primary endpoint). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2023.