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Active, not recruitingNCT01252953REVEALUpdated Jun 25, 2024Results posted

REVEAL: Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification

A Phase 3 interventional study of Anacetrapib and Placebo anacetrapib in Atherosclerotic Cardiovascular Disease, sponsored by University of Oxford. Active, not recruiting at 1 site in United Kingdom. Open to participants aged 50 Years and older. Per ClinicalTrials.gov, last updated 2024-06-25.

Sponsored by University of Oxford · Phase 3, Interventional, and Prevention

Phase
Phase 3
Study type
Interventional
Enrollment
30,449
Allocation
Randomized
Ages
50 Years and older
Sex
All
01

Study 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.

Read the detailed description

Sub-study: Does anacetrapib as a CETP inhibitor lead to mobilization of stem cells and enhance myocardial function via neoangiogenesis and tissue regeneration?

Following the main on-treatment part of the study, there was a further period of at least 2 years during which participants were followed-up by telephone, off treatment.

All participants stopped study treatment prior to February 2017 (results for the main-trial have been reported) and direct participant follow-up was completed in April 2019.

In the UK we will continue to collect information on health outcomes via central data registries and NHS sources for many years.

02

Conditions studied

  • Atherosclerotic Cardiovascular Disease

Keywords

  • vascular disease
  • lipids
  • cholesteryl ester transfer protein (CETP) inhibition
  • anacetrapib
03

In context

Atherosclerosis

1,596 studies on the registry are indexed under Atherosclerosis; 262 are open to participants now.

This study's enrollment of 30,449 is above the median of 105 across 898 interventional studies indexed under Atherosclerosis.

Browse Atherosclerosis studies →

Lead sponsor

University of Oxford is the lead sponsor of 812 studies on the registry; 119 are open to participants now.

Browse University of Oxford studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
50 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Patients must be aged at least 50 at the time of initial invitation, and at least one of the following inclusion criteria must be satisfied:

    • 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).

Exclusion criteria

Exclusion Criteria:

  • 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:

      1. macrolide antibiotics (erythromycin, clarithromycin, telithromycin);
      2. systemic imidazole or triazole antifungals (e.g. itraconazole, posaconazole);
      3. protease inhibitors (e.g. atazanavir);

      4. nefazodone

        (ii) ciclosporin

        (iii) daptomycin

        (iv) systemic use of fusidic acid

        Note: Individuals who are taking such drugs temporarily 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);
    • Women of child-bearing potential (unless using adequate contraception);
    • Current participation in a clinical trial with an unlicensed drug or device.

Individuals will also be excluded at the Screening visit if it is considered unlikely that they will achieve total cholesterol \<3.5 mmol/L (135 mg/dL) on the highest atorvastatin dose available in their region (atorvastatin 80 mg daily in non-Asian countries or 20 mg daily in North East Asia).

In addition, individuals will be excluded at the Randomization visit if any of the following are true:

  • Total cholesterol above 4 mmol/L [155 mg/dL]
  • Non-compliant with run-in treatment (\<90% scheduled run-in medication taken)
  • Individual is no longer willing to be randomized into the 4-5 year trial
  • The individual's doctor is of the view that their patient should not be randomized.
05

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
30,449 participants (actual)

Study arms

  • Experimental
    Anacetrapib

    Drug: Anacetrapib

  • Placebo comparator
    Placebo anacetrapib

    Drug: Placebo anacetrapib

Interventions

  • DrugAnacetrapib

    tablet, 100mg daily

  • DrugPlacebo anacetrapib

    tablet, 1 tablet daily

06

What researchers measure

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.

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

Secondary outcomes

  1. Number of Participants With Major Atherosclerotic Event

    Major atherosclerotic events (defined as coronary death, myocardial infarction or presumed ischaemic stroke; the key secondary outcome). Secondary assessments involve intention-to-treat comparisons among all randomized participants of the effects of allocation to anacetrapib versus placebo during the scheduled treatment period.

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

  2. Number of Participants With Presumed Ischaemic Stroke

    Presumed ischaemic stroke (i.e. not known to be haemorrhagic). Secondary assessments involve intention-to-treat comparisons among all randomized participants of the effects of allocation to anacetrapib versus placebo during the scheduled treatment period.

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

  3. Number of Participants With Major Vascular Event

    Major vascular events (defined as coronary death, myocardial infarction, coronary revascularization or presumed ischaemic stroke). Secondary assessments involve intention-to-treat comparisons among all randomized participants of the effects of allocation to anacetrapib versus placebo during the scheduled treatment period

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

07

Results

Posted May 4, 2018

Participant flow

Participants were randomized between August 2011 and October 2013. Follow-up continued until 31st January 2017.

Participant flow — Overall Study
MilestoneAnacetrapibPlacebo Anacetrapib
Started1522515224
Completed1518715186
Not completed3838
Withdrew: Withdrawal by subject1617
Withdrew: Lost to follow-up2221

Outcome measures

PrimaryNumber 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.

Time frame:
Randomized treatment phase during median follow-up period of 4.1years
Reported as:
Count of participants · Participants
Number of Participants With Major Coronary Event
ParticipantsAnacetrapibPlacebo Anacetrapib
Number of Participants With Major Coronary Event16401803
Statistical analysis
  • Anacetrapib vs Placebo Anacetrapib · Log Rank · p = 0.004 · Rate ratio: 0.91 · 95% CI 0.85 to 0.97
SecondaryNumber of Participants With Major Atherosclerotic Event

Major atherosclerotic events (defined as coronary death, myocardial infarction or presumed ischaemic stroke; the key secondary outcome). Secondary assessments involve intention-to-treat comparisons among all randomized participants of the effects of allocation to anacetrapib versus placebo during the scheduled treatment period.

Time frame:
Randomized treatment phase during median follow-up period of 4.1years
Reported as:
Count of participants · Participants
Number of Participants With Major Atherosclerotic Event
ParticipantsAnacetrapibPlacebo Anacetrapib
Number of Participants With Major Atherosclerotic Event13831483
Statistical analysis
  • Anacetrapib vs Placebo Anacetrapib · Log Rank · p = 0.052 · Rate ratio: 0.93 · 95% CI 0.86 to 1
SecondaryNumber of Participants With Presumed Ischaemic Stroke

Presumed ischaemic stroke (i.e. not known to be haemorrhagic). Secondary assessments involve intention-to-treat comparisons among all randomized participants of the effects of allocation to anacetrapib versus placebo during the scheduled treatment period.

Time frame:
Randomized treatment phase during median follow-up period of 4.1years
Reported as:
Count of participants · Participants
Number of Participants With Presumed Ischaemic Stroke
ParticipantsAnacetrapibPlacebo Anacetrapib
Number of Participants With Presumed Ischaemic Stroke485489
Statistical analysis
  • Anacetrapib vs Placebo Anacetrapib · Rate ratio: 0.99 · 95% CI 0.87 to 1.12
SecondaryNumber of Participants With Major Vascular Event

Major vascular events (defined as coronary death, myocardial infarction, coronary revascularization or presumed ischaemic stroke). Secondary assessments involve intention-to-treat comparisons among all randomized participants of the effects of allocation to anacetrapib versus placebo during the scheduled treatment period

Time frame:
Randomized treatment phase during median follow-up period of 4.1years
Reported as:
Count of participants · Participants
Number of Participants With Major Vascular Event
ParticipantsAnacetrapibPlacebo Anacetrapib
Number of Participants With Major Vascular Event20682214
Statistical analysis
  • Anacetrapib vs Placebo Anacetrapib · Log Rank · p = 0.02 · Rate ratio: 0.93 · 95% CI 0.88 to 0.99

Adverse events

Collected over Randomized treatment phase during median follow-up period of 4.1years. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Anacetrapib1,122/15,225 (7.4%)8,898/15,225 (58.4%)2,493/3,048 (81.8%)
Placebo Anacetrapib1,155/15,224 (7.6%)8,912/15,224 (58.5%)2,503/3,034 (82.5%)
Most frequent serious events
Showing 10 of 25
Most frequent serious events
EventAnacetrapibPlacebo Anacetrapib
Surgical and medical proceduresSurgical and medical procedures3409/152253478/15224
Cardiac disordersCardiac disorders2568/152252766/15224
Infections and infestationsInfections and infestations1559/152251537/15224
Nervous system disordersNervous system disorders1399/152251455/15224
Neoplasms benign, malignant and unspecified (incl cycts and polyps)Neoplasms benign, malignant and unspecified (incl cysts and polyps)1323/152251295/15224
InvestigationsInvestigations1105/152251135/15224
Gastrointestinal disordersGastrointestinal disorders813/15225788/15224
Injury, poisoning and procedural complicationsInjury, poisoning and procedural complications753/15225777/15224
General disorders & administration site conditionsGeneral disorders691/15225736/15224
Metabolism and nutrition disordersMetabolism and nutrition disorders642/15225687/15224
Most frequent other events
Showing 10 of 16
Most frequent other events
EventAnacetrapibPlacebo Anacetrapib
Musculoskeletal and connective tissue disordersMusculoskeletal and connective tissue disorders1125/30481105/3034
Infections and infestationsInfections and infestations974/3048943/3034
Nervous system disordersNervous system disorders625/3048623/3034
Gastrointestinal disordersGastrointestinal disorders596/3048557/3034
Injury, poisoning and procedural complicationsInjury, poisoning and procedural complications480/3048516/3034
Respiratory, thoracic and mediastinal disordersRespiratory, thoracic and mediastinal disorders463/3048412/3034
Metabolism and nutrition disordersMetabolism and nutrition disorders405/3048393/3034
General disorders and administration site conditionsGeneral disorders321/3048338/3034
InvestigationsInvestigations327/3048307/3034
Eye disordersEye disorders227/3048230/3034

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)AnacetrapibPlacebo AnacetrapibTotal
<=18 years000
Between 18 and 65 years6634664313277
>=65 years8591858117172
Age, Continuous
Age, Continuous(years)AnacetrapibPlacebo AnacetrapibTotal
Mean67 ± 867 ± 867 ± 8
Sex: Female, Male
Sex: Female, Male(Participants)AnacetrapibPlacebo AnacetrapibTotal
Female245624594915
Male127691276525534
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)AnacetrapibPlacebo AnacetrapibTotal
Hispanic or Latino121114235
Not Hispanic or Latino256025225082
Unknown or Not Reported125441258825132
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)AnacetrapibPlacebo AnacetrapibTotal
Race — Black or African American160168328
Race — Chinese432343238646
Race — Other North East Asian5611
Race — South Asian9597192
Race — South East Asian111122
Race — White105611055821119
Race — Other474996
Race — Mixed211233
Race — Unknown202
Region of Enrollment
Region of Enrollment(participants)AnacetrapibPlacebo AnacetrapibTotal
United Kingdom420441778381
Norway426418844
Sweden427434861
Denmark9189321850
Finland307306613
Germany7557741529
Italy8268341660
United States268726435330
Canada361391752
China431443158629
Previous disease
Previous disease(Participants)AnacetrapibPlacebo AnacetrapibTotal
Coronary heart disease133251335426679
Cerebrovascular disease338533966781
Peripheral-artery disease122912062435
Diabetes5654566611320
Heart failure9028691771
Region
Region(Participants)AnacetrapibPlacebo AnacetrapibTotal
Europe7863787515738
North America304830346082
China431443158629

14 further baseline measures are reported on the registry.

08

Study locations

1 site
  • CTSU, University of Oxford
    Oxford, Oxfordshire OX3 7LF, United Kingdom
09

References and documents

Publications

  • 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. PubMed 28454801 ↗
  • 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. PubMed 28847206 ↗
  • 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. PubMed 31331193 ↗
  • 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. PubMed 34910136 ↗
  • 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. PubMed 37750555 ↗
  • Castonguay M, Anderson MA, Thompson P, Seymour JF. Venetoclax retreatment in chronic lymphocytic leukemia is biologically rational and clinically effective. Blood Adv. 2026 May 26;10(10):3357-3366. doi: 10.1182/bloodadvances.2026019871. PubMed 41843779 ↗
  • 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. PubMed 22696435 ↗
  • 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. PubMed 22180633 ↗

Study documents

  • Study protocol · Jan 11, 2016
  • Statistical analysis plan · May 12, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — 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.

Supporting information: Study protocol, Statistical analysis plan

Access criteria: See URL

Data sharing details ↗ · www.ndph.ox.ac.uk

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 25, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01252953
Lead sponsor
University of Oxford
Collaborators
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
Dec 3, 2010
Start date
Jun 2011
Primary completion
Jan 31, 2017
Completion
Jan 31, 2037 (estimated)
Results posted
May 4, 2018
Last update
Jun 25, 2024

Study contacts

Martin Landray
principal investigator · University of Oxford
Louise Bowman
principal investigator · University of Oxford

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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