NCT00461630

Brief Summary

The primary aim is to assess the effects of raising HDL cholesterol (the good type) with extended release niacin/laropiprant 2g (previously known as MK-0524A) versus matching placebo on the risk of heart attack or coronary death, stroke, or the need for arterial bypass procedures (revascularisation) in people with a history of circulatory problems. The secondary aim is to assess the effects of extended release niacin/laropiprant 2g daily on heart attack, coronary death, stroke, and revascularisation separately and to assess the effects on mortality both overall and in various categories of causes of death, and of the effects on major cardiovascular events in people with a history of different diseases at the beginning of the study.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
25,673

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Jan 2007

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2007

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

April 17, 2007

Completed
1 day until next milestone

First Posted

Study publicly available on registry

April 18, 2007

Completed
5.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2012

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

January 28, 2014

Completed
Last Updated

February 28, 2014

Status Verified

January 1, 2014

Enrollment Period

5.8 years

First QC Date

April 17, 2007

Results QC Date

July 12, 2013

Last Update Submit

January 27, 2014

Conditions

Cardiovascular DiseasePeripheral Arterial DiseaseDiabetes MellitusCoronary Heart Disease

Keywords

coronary heart diseasecardiovascular diseasestrokeperipheral arterial diseasediabetes mellituscholesterolHDL cholesterolsimvastatinezetimibeER niacinlaropiprant

Outcome Measures

Primary Outcomes (1)

  • Major Vascular Event

    Non-fatal myocardial infarction or coronary death, non-fatal or fatal stroke, or revascularisation

    During scheduled treatment period (median duration 3.9 years)

Secondary Outcomes (4)

  • Major Coronary Events

    During scheduled treatment period (median duration 3.9 years)

  • Stroke

    During scheduled treatment period (median duration 3.9 years)

  • Coronary or Non-coronary Revascularisation

    During scheduled treatment period (median duration 3.9 years)

  • Mortality

    During scheduled treatment period (median duration 3.9 years)

Study Arms (2)

ER niacin/laropiprant

EXPERIMENTAL

1 g ER niacin plus 20 mg laropiprant per tablet. 2 tablets orally per day. With either 40 mg simvastatin tablet or ezetimibe/simvastatin (10 mg/40 mg) in single tablet taken once daily

Drug: ER niacin/laropiprantDrug: simvastatinDrug: ezetimibe/simvastatin

Placebo

ACTIVE COMPARATOR

Placebo (for ER niacin/laropiprant) 2 tablets orally per day. With either 40 mg simvastatin tablet orally per day or ezetimibe/simvastatin (10 mg/40 mg) in single tablet taken once daily

Drug: simvastatinDrug: ezetimibe/simvastatin

Interventions

ER niacin/laropiprantDRUG
Also known as: Tredaptive
ER niacin/laropiprant
simvastatinDRUG

40 mg simvastatin tablet orally per day as background LDL-lowering treatment allocated at entry based on previous statin treatment and total cholesterol level

Also known as: Zocor
ER niacin/laropiprantPlacebo
ezetimibe/simvastatinDRUG

10 mg ezetimibe plus 40 mg simvastatin in single tablet taken once daily as background LDL-lowering treatment allocated at entry based on previous statin treatment and total cholesterol level

Also known as: Inegy, Vytorin
ER niacin/laropiprantPlacebo

Eligibility Criteria

Age50 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • History of myocardial infarction; or
  • Cerebrovascular atherosclerotic disease (history of presumed ischaemic stroke, transient ischaemic attack or carotid revascularisation)
  • Peripheral arterial disease (i.e. intermittent claudication or history of revascularisation); or
  • Diabetes mellitus with any of the above or with other evidence of symptomatic coronary heart disease (i.e. stable or unstable angina, or a history of coronary revascularisation or acute coronary syndrome).

You may not qualify if:

  • Age \<50 or \>80 years at invitation to Screening;
  • Less than 3 months since presentation with acute myocardial infarction, coronary syndrome or stroke (but such patients may be entered later, if appropriate);
  • Planned revascularisation procedure within 3 months after randomization (but such patients may be entered later, if appropriate);
  • Definite history of chronic liver disease, or abnormal liver function (i.e. Alanine transaminase (ALT) \>1.5 times upper limit of normal (ULN). (Note: Patients with a history of acute hepatitis are eligible provided this ALT limit is not exceeded);
  • Breathlessness at rest for any reason;
  • Severe renal insufficiency (i.e. creatinine \>200 µmol/L);
  • Evidence of active inflammatory muscle disease (e.g. dermatomyositis, polymyositis), or Creatine kinase (CK) \>3 times upper limit of normal (3xULN);
  • Previous significant adverse reaction to a statin, ezetimibe, niacin or laropiprant;
  • Active peptic ulcer disease;
  • Concurrent treatment with:
  • fibric acid derivative ("fibrate")
  • niacin (nicotinic acid) at doses more than 100 mg daily
  • ezetimibe in combination with either simvastatin 80 mg, or atorvastatin 20-80 mg, or rosuvastatin 10-40 mg daily
  • any potent cytochrome P450 3A4 (CYP3A4) inhibitor, including: macrolide antibiotics (erythromycin, clarithromycin, telithromycin); systemic use of imidazole or triazole antifungals (e.g. itraconazole, ketoconazole); protease inhibitors (antiretroviral drugs for HIV infection); and nefazodone
  • ciclosporin
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Clinical Trial Service Unit, University of Oxford

Oxford, OX3 7LF, United Kingdom

Location

Related Publications (6)

  • HPS2-THRIVE Collaborative Group; Haynes R, Chen F, Wincott E, Dayanandan R, Lay MJ, Parish S, Bowman L, Landray MJ, Armitage J. Investigating modifications to participant information materials to improve recruitment into a large randomized trial. Trials. 2019 Dec 5;20(1):681. doi: 10.1186/s13063-019-3779-4.

    PMID: 31805983DERIVED

  • Haynes R, Valdes-Marquez E, Hopewell JC, Chen F, Li J, Parish S, Landray MJ, Armitage J; HPS2-THRIVE Collaborative Group; HPS2-THRIVE Writing Committee members; HPS2-THRIVE Steering Committee members. Serious Adverse Effects of Extended-release Niacin/Laropiprant: Results From the Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) Trial. Clin Ther. 2019 Sep;41(9):1767-1777. doi: 10.1016/j.clinthera.2019.06.012. Epub 2019 Aug 22.

    PMID: 31447131DERIVED

  • Offer A, Arnold M, Clarke R, Bennett D, Bowman L, Bulbulia R, Haynes R, Li J, Hopewell JC, Landray M, Armitage J, Collins R, Parish S; Heart Protection Study (HPS), Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH), and Treatment of HDL (High-Density Lipoprotein) to Reduce the Incidence of Vascular Events (HPS2-THRIVE) Collaborative Grou. Assessment of Vascular Event Prevention and Cognitive Function Among Older Adults With Preexisting Vascular Disease or Diabetes: A Secondary Analysis of 3 Randomized Clinical Trials. JAMA Netw Open. 2019 Mar 1;2(3):e190223. doi: 10.1001/jamanetworkopen.2019.0223.

    PMID: 30821829DERIVED

  • Parish S, Hopewell JC, Hill MR, Marcovina S, Valdes-Marquez E, Haynes R, Offer A, Pedersen TR, Baigent C, Collins R, Landray M, Armitage J; HPS2-THRIVE Collaborative Group. Impact of Apolipoprotein(a) Isoform Size on Lipoprotein(a) Lowering in the HPS2-THRIVE Study. Circ Genom Precis Med. 2018 Feb;11(2):e001696. doi: 10.1161/CIRCGEN.117.001696.

    PMID: 29449329DERIVED

  • Kent S, Haynes R, Hopewell JC, Parish S, Gray A, Landray MJ, Collins R, Armitage J, Mihaylova B; HPS2-THRIVE Collaborative Group. Effects of Vascular and Nonvascular Adverse Events and of Extended-Release Niacin With Laropiprant on Health and Healthcare Costs. Circ Cardiovasc Qual Outcomes. 2016 Jul;9(4):348-54. doi: 10.1161/CIRCOUTCOMES.115.002592. Epub 2016 Jul 12.

    PMID: 27407053DERIVED

  • HPS2-THRIVE Collaborative Group; Landray MJ, Haynes R, Hopewell JC, Parish S, Aung T, Tomson J, Wallendszus K, Craig M, Jiang L, Collins R, Armitage J. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014 Jul 17;371(3):203-12. doi: 10.1056/NEJMoa1300955.

    PMID: 25014686DERIVED

MeSH Terms

Conditions

Cardiovascular DiseasesPeripheral Arterial DiseaseDiabetes MellitusCoronary DiseaseStroke

Interventions

MK-0524SimvastatinEzetimibe, Simvastatin Drug Combination

Condition Hierarchy (Ancestors)

AtherosclerosisArteriosclerosisArterial Occlusive DiseasesVascular DiseasesPeripheral Vascular DiseasesGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesMyocardial IschemiaHeart DiseasesCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System Diseases

Intervention Hierarchy (Ancestors)

LovastatinNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsEzetimibeAzetidinesAzetinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsDrug CombinationsPharmaceutical Preparations

Limitations and Caveats

Participants may have SAEs reported in \>1 category hence total participants affected across reported categories is less than total given.

Results Point of Contact

Title
Professor Jane Armitage
Organization
Clinical Trial Service Unit, University of Oxford
thrive@ctsu.ox.ac.uk
+44 (0)1865 743743

Study Officials

  • Jane Armitage

    Clinical Trial Service Unit, University of Oxford

    PRINCIPAL INVESTIGATOR

  • Colin Baigent

    Clinical Trial service Unit, University of Oxford

    PRINCIPAL INVESTIGATOR

  • Zhengming Chen

    Clinical Trial Service Unit, University of Oxford

    PRINCIPAL INVESTIGATOR

  • Martin Landray

    Clinical Trial Service Unit, University of Oxford

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Clinical trials and Epidemiology, Clinical trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Clinical Medicine, University of Oxford

Study Record Dates

First Submitted

April 17, 2007

First Posted

April 18, 2007

Study Start

January 1, 2007

Primary Completion

October 1, 2012

Study Completion

October 1, 2012

Last Updated

February 28, 2014

Results First Posted

January 28, 2014

Record last verified: 2014-01

Locations

GB(1)