NCT01252953

Brief Summary

The Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification (REVEAL) trial aims to determine whether lipid modification with anacetrapib 100mg daily reduces the risk of coronary death, myocardial infarction (MI) or coronary revascularization (collectively known as major coronary events) in patients with circulatory problems who have their Low-density Lipoprotein (LDL) cholesterol level treated with a statin.

Trial Health

75
On Track

Trial Health Score

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

Enrollment
30,449

participants targeted

Target at P75+ for phase_3

Timeline
131mo left

Started Jun 2011

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
active not recruiting

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 Progress58%
Jun 2011Jan 2037

First Submitted

Initial submission to the registry

November 24, 2010

Completed
9 days until next milestone

First Posted

Study publicly available on registry

December 3, 2010

Completed
6 months until next milestone

Study Start

First participant enrolled

June 1, 2011

Completed
5.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 31, 2017

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

May 4, 2018

Completed
18.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 31, 2037

Expected
Last Updated

June 25, 2024

Status Verified

June 1, 2024

Enrollment Period

5.7 years

First QC Date

November 24, 2010

Results QC Date

February 1, 2018

Last Update Submit

June 11, 2024

Conditions

Atherosclerotic Cardiovascular Disease

Keywords

vascular diseaselipidscholesteryl ester transfer protein (CETP) inhibitionanacetrapib

Outcome Measures

Primary Outcomes (1)

  • Number of Participants With Major Coronary Event

    Primary assessment involves an intention-to-treat comparison among all randomized participants of the effects of allocation to anacetrapib versus placebo on major coronary events (defined as the occurrence of coronary death, myocardial infarction or coronary revascularization procedure) during the scheduled treatment period. Data reported is for the first major coronary event.

    Randomized treatment phase during median follow-up period of 4.1years

Secondary Outcomes (3)

  • Number of Participants With Major Atherosclerotic Event

    Randomized treatment phase during median follow-up period of 4.1years

  • Number of Participants With Presumed Ischaemic Stroke

    Randomized treatment phase during median follow-up period of 4.1years

  • Number of Participants With Major Vascular Event

    Randomized treatment phase during median follow-up period of 4.1years

Study Arms (2)

Anacetrapib

EXPERIMENTAL
Drug: Anacetrapib

Placebo anacetrapib

PLACEBO COMPARATOR
Drug: Placebo anacetrapib

Interventions

AnacetrapibDRUG

tablet, 100mg daily

Anacetrapib
Placebo anacetrapibDRUG

tablet, 1 tablet daily

Placebo anacetrapib

Eligibility Criteria

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

You may qualify if:

  • History of MI; or
  • Cerebrovascular atherosclerotic disease (i.e. history of presumed ischaemic stroke or carotid revascularization); or
  • Peripheral arterial disease (i.e. history of non-coronary revascularization, including aortic aneurysm repair or graft); or
  • Diabetes mellitus with other evidence of symptomatic coronary heart disease (i.e. treatment or hospitalization for angina, or a history of coronary revascularization or acute coronary syndrome).

You may not qualify if:

  • None of the following must be satisfied:
  • Acute MI, acute coronary syndrome or stroke within 4 weeks prior to Screening Visit or during Run-in (but such individuals may be entered later, if appropriate);
  • Planned coronary revascularization procedure within the next 6 months (such individuals may be entered later, if appropriate);
  • Definite history of chronic liver disease, or abnormal liver function (i.e. alanine transaminase (ALT) \>2x the upper limit of normal (ULN)). Note: Individuals with a history of acute hepatitis are eligible provided this ALT limit is not exceeded;
  • Severe renal insufficiency (i.e. creatinine \>200 µmol/L \[2.3 mg/dL\], dialysis or functioning renal transplant);
  • Evidence of active inflammatory muscle disease (e.g. dermatomyositis, polymyositis), or creatine kinase (CK) \>3x ULN;
  • Previous significant adverse reaction to a statin or anacetrapib;
  • Current treatment with any of the following lipid-lowering treatments:
  • (i) a regimen considered to produce substantially greater LDL cholesterol reduction than atorvastatin 80 mg daily for individuals in non-Asian countries or 20 mg daily for those in North East Asia; or (ii) fibric acid derivative ("fibrate", including gemfibrozil); or (iii) niacin (nicotinic acid) at doses above 100 mg daily
  • Concurrent treatment with a medication that is contraindicated with anacetrapib or atorvastatin:
  • (i) any potent CYP3A4 inhibitor, such as:
  • macrolide antibiotics (erythromycin, clarithromycin, telithromycin);
  • systemic imidazole or triazole antifungals (e.g. itraconazole, posaconazole);
  • protease inhibitors (e.g. atazanavir);
  • nefazodone
  • +14 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

CTSU, University of Oxford

Oxford, Oxfordshire, OX3 7LF, United Kingdom

Location

Related Publications (7)

  • REVEAL Collaborative Group; Bowman L, Chen F, Sammons E, Hopewell JC, Wallendszus K, Stevens W, Valdes- Marquez E, Wiviott S, Cannon CP, Braunwald E, Collins R, Landray MJ. Randomized Evaluation of the Effects of Anacetrapib through Lipid-modification (REVEAL)-A large-scale, randomized, placebo-controlled trial of the clinical effects of anacetrapib among people with established vascular disease: Trial design, recruitment, and baseline characteristics. Am Heart J. 2017 May;187:182-190. doi: 10.1016/j.ahj.2017.02.021. Epub 2017 Feb 21.

    PMID: 28454801BACKGROUND

  • HPS3/TIMI55-REVEAL Collaborative Group; Bowman L, Hopewell JC, Chen F, Wallendszus K, Stevens W, Collins R, Wiviott SD, Cannon CP, Braunwald E, Sammons E, Landray MJ. Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease. N Engl J Med. 2017 Sep 28;377(13):1217-1227. doi: 10.1056/NEJMoa1706444. Epub 2017 Aug 28.

    PMID: 28847206RESULT

  • Hopewell JC, Ibrahim M, Hill M, Shaw PM, Braunwald E, Blaustein RO, Bowman L, Landray MJ, Sabatine MS, Collins R; HPS3/TIMI55-REVEAL Collaborative Group. Impact of ADCY9 Genotype on Response to Anacetrapib. Circulation. 2019 Sep 10;140(11):891-898. doi: 10.1161/CIRCULATIONAHA.119.041546. Epub 2019 Jul 23.

    PMID: 31331193RESULT

  • HPS3/TIMI55-REVEAL Collaborative Group; Writing Committee; Sammons E, Hopewell JC, Chen F, Stevens W, Wallendszus K, Valdes-Marquez E, Dayanandan R, Knott C, Murphy K, Wincott E, Baxter A, Goodenough R, Lay M, Hill M, Macdonnell S, Fabbri G, Lucci D, Fajardo-Moser M, Brenner S, Hao D, Zhang H, Liu J, Wuhan B, Mosegaard S, Herrington W, Wanner C, Angermann C, Ertl G, Maggioni A, Barter P, Mihaylova B, Mitchel Y, Blaustein R, Goto S, Tobert J, DeLucca P, Chen Y, Chen Z, Gray A, Haynes R, Armitage J, Baigent C, Wiviott S, Cannon C, Braunwald E, Collins R, Bowman L, Landray M; REVEAL Collaborative Group. Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease. Eur Heart J. 2022 Apr 6;43(14):1416-1424. doi: 10.1093/eurheartj/ehab863.

    PMID: 34910136RESULT

  • Lui JNM, Williams C, Keng MJ, Hopewell JC, Sammons E, Chen F, Gray A, Bowman L, Landray SMJ, Mihaylova B; REVEAL Collaborative Group. Impact of New Cardiovascular Events on Quality of Life and Hospital Costs in People With Cardiovascular Disease in the United Kingdom and United States. J Am Heart Assoc. 2023 Oct 3;12(19):e030766. doi: 10.1161/JAHA.123.030766. Epub 2023 Sep 26.

    PMID: 37750555RESULT

  • Landmesser U, von Eckardstein A, Kastelein J, Deanfield J, Luscher TF. Increasing high-density lipoprotein cholesterol by cholesteryl ester transfer protein-inhibition: a rocky road and lessons learned? The early demise of the dal-HEART programme. Eur Heart J. 2012 Jul;33(14):1712-5. doi: 10.1093/eurheartj/ehs182. Epub 2012 Jun 13. No abstract available.

    PMID: 22696435DERIVED

  • Krauss RM, Wojnooski K, Orr J, Geaney JC, Pinto CA, Liu Y, Wagner JA, Luk JM, Johnson-Levonas AO, Anderson MS, Dansky HM. Changes in lipoprotein subfraction concentration and composition in healthy individuals treated with the CETP inhibitor anacetrapib. J Lipid Res. 2012 Mar;53(3):540-547. doi: 10.1194/jlr.M018010. Epub 2011 Dec 17.

    PMID: 22180633DERIVED

Related Links

MeSH Terms

Conditions

AtherosclerosisVascular DiseasesInhibition, Psychological

Interventions

anacetrapib

Condition Hierarchy (Ancestors)

ArteriosclerosisArterial Occlusive DiseasesCardiovascular DiseasesBehavior

Results Point of Contact

Title
Prof Martin Landray
Organization
Nuffield Department of Population Health, University of Oxford
martin.landray@ndph.ox.ac.uk
+44 (0)1865 743743

Study Officials

  • Martin Landray

    University of Oxford

    PRINCIPAL INVESTIGATOR

  • Louise Bowman

    University of Oxford

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

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
SPONSOR

Study Record Dates

First Submitted

November 24, 2010

First Posted

December 3, 2010

Study Start

June 1, 2011

Primary Completion

January 31, 2017

Study Completion (Estimated)

January 31, 2037

Last Updated

June 25, 2024

Results First Posted

May 4, 2018

Record last verified: 2024-06

Data Sharing

IPD Sharing
Will share

Proposals for substudies must be approved by the Steering Committee. Procedures for accessing the data for this study are available on: https://www.ndph.ox.ac.uk/data-access.

Shared Documents
STUDY PROTOCOL, SAP
Access Criteria
See URL
More information

Locations

GB(1)