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Treatment of HDL to Reduce the Incidence of Vascular Events HPS2-THRIVE (HPS2-THRIVE)

27. januar 2014 opdateret af: Jane Armitage, University of Oxford

A Randomized Trial of the Long-term Clinical Effects of Raising HDL Cholesterol With Extended Release Niacin/Laropiprant

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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

Cardiovascular disease is one of the leading causes of morbidity and mortality in the United Kingdom (UK), as well as in the developed and the developing world. Finding new and safe treatments to reduce the burden of heart disease and strokes is therefore an important contribution to public health and in the wider public interest. HPS2-THRIVE aims to find out whether by combining niacin (a drug that has been available for 50 years) with a new drug laropiprant(which reduces the side-effects of niacin) is beneficial. All participants in HPS2-THRIVE will have established cardiovascular disease and therefore be at very high risk of recurrent vascular events (myocardial infarction, stroke or the need for arterial revascularisation). Two of the most important risk factors for recurrent events in such patients are the blood levels of LDL cholesterol with a positive association, and HDL cholesterol levels with a negative association.

HDL cholesterol has long been known to have a strong inverse correlation with coronary heart disease (CHD) risk. But, randomized trial evidence for beneficial effects from raising HDL cholesterol is limited. One of the most effective HDL-raising agents is niacin but the tolerability of niacin has been severely limited by flushing and cutaneous side-effects, which appear to be mediated largely by prostaglandin D. Laropiprant is a selective prostaglandin D receptor antagonist that substantially reduces the frequency and intensity of niacin-induced flushing. Daily oral doses of extended release (ER) niacin plus Laropiprant 2g(formerly MK-0524A) have been well tolerated in early studies and increase HDL cholesterol by 20-25%. The trial will assess whether this increase in HDL cholesterol translates into clinical benefit as is expected from the observational evidence. In addition, all participants will also be provided with effective LDL-lowering therapy, as either simvastatin 40mg daily alone or with ezetimibe 10mg daily in a combination tablet.

The complementary effects on the HDL (good) and LDL (bad) cholesterol produced by extended release niacin/laropiprant 2 g daily and simvastatin 40 mg with or without ezetimibe 10 mg should provide an excellent treatment option for patients with vascular disease. However, no trials so far have demonstrated clearly that raising HDL cholesterol produces the expected reduction in cardiovascular risk. If HPS2-THRIVE is able to demonstrate reliably that raising HDL cholesterol reduces the risk of further cardiovascular events then this will be relevant to hundreds of millions of people worldwide.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

25673

Fase

  • Fase 3

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Det Forenede Kongerige
      • Oxford, Det Forenede Kongerige, OX3 7LF
        • Clinical Trial Service Unit, University of Oxford

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

50 år til 80 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • 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
  • amiodarone
  • verapamil
  • danazol (Note: Patients who are temporarily taking such drugs may be re-screened when they discontinue them, if considered appropriate.);
  • Known to be poorly compliant with clinic visits or prescribed medication;
  • Medical history that might limit the individual's ability to take trial treatments for the duration of the study (e.g. severe respiratory disease, history of cancer or evidence of spread within last 5 years other than non-melanoma skin cancer, or recent history of alcohol or substance misuse)

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Forebyggelse
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Firedobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: ER niacin/laropiprant
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
Medicin: ER niacin/laropiprant
Andre navne:
  • Tredaptive
Medicin: simvastatin
40 mg simvastatin tablet orally per day as background LDL-lowering treatment allocated at entry based on previous statin treatment and total cholesterol level
Andre navne:
  • Zocor
Medicin: ezetimibe/simvastatin
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
Andre navne:
  • Vytorin
  • Inegy
Aktiv komparator: Placebo
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
Medicin: simvastatin
40 mg simvastatin tablet orally per day as background LDL-lowering treatment allocated at entry based on previous statin treatment and total cholesterol level
Andre navne:
  • Zocor
Medicin: ezetimibe/simvastatin
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
Andre navne:
  • Vytorin
  • Inegy

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Major Vascular Event
Tidsramme: During scheduled treatment period (median duration 3.9 years)
Non-fatal myocardial infarction or coronary death, non-fatal or fatal stroke, or revascularisation
During scheduled treatment period (median duration 3.9 years)

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Major Coronary Events
Tidsramme: During scheduled treatment period (median duration 3.9 years)
Non-fatal myocardial infarction (MI) or coronary death
During scheduled treatment period (median duration 3.9 years)
Stroke
Tidsramme: During scheduled treatment period (median duration 3.9 years)
Fatal or non-fatal
During scheduled treatment period (median duration 3.9 years)
Coronary or Non-coronary Revascularisation
Tidsramme: During scheduled treatment period (median duration 3.9 years)
During scheduled treatment period (median duration 3.9 years)
Mortality
Tidsramme: During scheduled treatment period (median duration 3.9 years)
All-cause mortality
During scheduled treatment period (median duration 3.9 years)

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

University of Oxford

Samarbejdspartnere

Merck Sharp & Dohme LLC

Efterforskere

  • Ledende efterforsker: Jane Armitage, Clinical Trial Service Unit, University of Oxford
  • Ledende efterforsker: Colin Baigent, Clinical Trial Service Unit, University of Oxford
  • Ledende efterforsker: Zhengming Chen, Clinical Trial Service Unit, University of Oxford
  • Ledende efterforsker: Martin Landray, Clinical Trial Service Unit, University of Oxford

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. januar 2007

Primær færdiggørelse (Faktiske)

1. oktober 2012

Studieafslutning (Faktiske)

1. oktober 2012

Datoer for studieregistrering

Først indsendt

17. april 2007

Først indsendt, der opfyldte QC-kriterier

17. april 2007

Først opslået (Skøn)

18. april 2007

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

28. februar 2014

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

27. januar 2014

Sidst verificeret

1. januar 2014

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • CTSUTHRIVE1
  • ISRCTN29503772
  • 2006-001885-17 (EudraCT nummer)

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Kardiovaskulær sygdom

Kliniske forsøg med ER niacin/laropiprant

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Sponsorer og samarbejdspartnere

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Narkotikainterventioner

CROs by country

CROs in Ecuador

Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

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