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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01252953
Recruitment Status : Active, not recruiting
First Posted : December 3, 2010
Results First Posted : May 4, 2018
Last Update Posted : March 18, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of Oxford

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Atherosclerotic Cardiovascular Disease
Interventions Drug: Anacetrapib
Drug: Placebo anacetrapib
Enrollment 30449
Recruitment Details Participants were randomized between August 2011 and October 2013. Follow-up continued until 31st January 2017.
Pre-assignment Details Successfully screened participants were entered into a run-in period. Attendees were discouraged from continuing to randomization if it was thought unlikely they would be able to continue attending follow-up visits for at least 4-5years. During run-in participants were issued atorvastatin (1 tablet/day) and placebo anacetrapib (1 tablet/day).
Arm/Group Title Anacetrapib Placebo Anacetrapib
Hide Arm/Group Description Anacetrapib: 100mg tablet daily Placebo anacetrapib: 1 tablet daily
Period Title: Overall Study
Started 15225 15224
Completed 15187 15186
Not Completed 38 38
Reason Not Completed
Withdrawal by Subject             16             17
Lost to Follow-up             22             21
Arm/Group Title Anacetrapib Placebo Anacetrapib Total
Hide Arm/Group Description Anacetrapib: 100mg tablet daily Placebo anacetrapib: 1 tablet daily Total of all reporting groups
Overall Number of Baseline Participants 15225 15224 30449
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15225 participants 15224 participants 30449 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
6634
  43.6%
6643
  43.6%
13277
  43.6%
>=65 years
8591
  56.4%
8581
  56.4%
17172
  56.4%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15225 participants 15224 participants 30449 participants
67  (8) 67  (8) 67  (8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15225 participants 15224 participants 30449 participants
Female
2456
  16.1%
2459
  16.2%
4915
  16.1%
Male
12769
  83.9%
12765
  83.8%
25534
  83.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15225 participants 15224 participants 30449 participants
Hispanic or Latino
121
   0.8%
114
   0.7%
235
   0.8%
Not Hispanic or Latino
2560
  16.8%
2522
  16.6%
5082
  16.7%
Unknown or Not Reported
12544
  82.4%
12588
  82.7%
25132
  82.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 15225 participants 15224 participants 30449 participants
Black or African American
160
   1.1%
168
   1.1%
328
   1.1%
Chinese
4323
  28.4%
4323
  28.4%
8646
  28.4%
Other North East Asian
5
   0.0%
6
   0.0%
11
   0.0%
South Asian
95
   0.6%
97
   0.6%
192
   0.6%
South East Asian
11
   0.1%
11
   0.1%
22
   0.1%
White
10561
  69.4%
10558
  69.4%
21119
  69.4%
Other
47
   0.3%
49
   0.3%
96
   0.3%
Mixed
21
   0.1%
12
   0.1%
33
   0.1%
Unknown
2
   0.0%
0
   0.0%
2
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15225 participants 15224 participants 30449 participants
United Kingdom 4204 4177 8381
Norway 426 418 844
Sweden 427 434 861
Denmark 918 932 1850
Finland 307 306 613
Germany 755 774 1529
Italy 826 834 1660
United States 2687 2643 5330
Canada 361 391 752
China 4314 4315 8629
Previous disease   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15225 participants 15224 participants 30449 participants
Coronary heart disease
13325
  87.5%
13354
  87.7%
26679
  87.6%
Cerebrovascular disease
3385
  22.2%
3396
  22.3%
6781
  22.3%
Peripheral-artery disease
1229
   8.1%
1206
   7.9%
2435
   8.0%
Diabetes
5654
  37.1%
5666
  37.2%
11320
  37.2%
Heart failure
902
   5.9%
869
   5.7%
1771
   5.8%
[1]
Measure Description: The participants could have more than one of these conditions.
Region  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15225 participants 15224 participants 30449 participants
Europe
7863
  51.6%
7875
  51.7%
15738
  51.7%
North America
3048
  20.0%
3034
  19.9%
6082
  20.0%
China
4314
  28.3%
4315
  28.3%
8629
  28.3%
Systolic Blood Pressure, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15225 participants 15224 participants 30449 participants
<125 mmHg
5678
  37.3%
5760
  37.8%
11438
  37.6%
≥125 to <140 mmHg
4819
  31.7%
4740
  31.1%
9559
  31.4%
≥140 mmHg
4728
  31.1%
4724
  31.0%
9452
  31.0%
Systolic Blood Pressure, Continuous  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 15225 participants 15224 participants 30449 participants
131.3  (18.5) 131.1  (18.5) 131.2  (18.5)
Diastolic Blood Pressure, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15225 participants 15224 participants 30449 participants
< 75 mmHg
5656
  37.1%
5790
  38.0%
11446
  37.6%
≥ 75 to < 85 mmHg
5408
  35.5%
5277
  34.7%
10685
  35.1%
≥ 85 mmHg
4161
  27.3%
4157
  27.3%
8318
  27.3%
Diastolic Blood Pressure, Continuous  
Mean (Standard Deviation)
Unit of measure:  mmHg
Number Analyzed 15225 participants 15224 participants 30449 participants
78.1  (10.9) 78.0  (11.0) 78.1  (11.0)
Body Mass Index, Categorical   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15225 participants 15224 participants 30449 participants
<25 kg/m^2
3447
  22.6%
3361
  22.1%
6808
  22.4%
≥25 to < 30 kg/m^2
6949
  45.6%
6995
  45.9%
13944
  45.8%
≥ 30 kg/m^2
4829
  31.7%
4868
  32.0%
9697
  31.8%
[1]
Measure Description: The body mass index is the weight in kilograms divided by the square of the height in meters.
Body Mass Index, Continuous  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 15225 participants 15224 participants 30449 participants
28.6  (5.0) 28.6  (5.1) 28.6  (5.1)
LDL Cholesterol, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15225 participants 15224 participants 30449 participants
< 54 mg/dl
5023
  33.0%
5077
  33.3%
10100
  33.2%
≥ 54 to < 66 mg/dl
4643
  30.5%
4705
  30.9%
9348
  30.7%
≥ 66 mg/dl
5559
  36.5%
5442
  35.7%
11001
  36.1%
LDL Cholesterol, Continuous  
Mean (Standard Deviation)
Unit of measure:  Mg/dl
Number Analyzed 15225 participants 15224 participants 30449 participants
61  (15) 61  (15) 61  (15)
Non-HDL Cholesterol, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15225 participants 15224 participants 30449 participants
< 85 mg/dl
5642
  37.1%
5701
  37.4%
11343
  37.3%
≥ 85 to <101 mg/dl
4896
  32.2%
4853
  31.9%
9749
  32.0%
≥ 101 mg/dl
4687
  30.8%
4670
  30.7%
9357
  30.7%
Non-HDL Cholesterol, Continuous  
Mean (Standard Deviation)
Unit of measure:  Mg/dl
Number Analyzed 15225 participants 15224 participants 30449 participants
92  (19) 92  (19) 92  (19)
HDL Cholesterol, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15225 participants 15224 participants 30449 participants
< 35 mg/dl
4583
  30.1%
4590
  30.1%
9173
  30.1%
≥ 35 to < 43 mg/dl
5438
  35.7%
5269
  34.6%
10707
  35.2%
≥ 43 mg/dl
5204
  34.2%
5365
  35.2%
10569
  34.7%
HDL Cholesterol, Continuous  
Mean (Standard Deviation)
Unit of measure:  Mg/dl
Number Analyzed 15225 participants 15224 participants 30449 participants
40  (10) 40  (10) 40  (10)
Glomerular Filtration Rate, Categorical   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15225 participants 15224 participants 30449 participants
< 60 ml/min/1.73m^2
1655
  10.9%
1698
  11.2%
3353
  11.0%
≥ 60 ml/min/1.73m^2
13570
  89.1%
13526
  88.8%
27096
  89.0%
[1]
Measure Description:

The estimated glomerular filtration rate was calculated with the use of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation as per Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate.

Ann Intern Med 2009; 150(9): 604-12.

Glomerular Filtration Rate, Continuous  
Mean (Standard Deviation)
Unit of measure:  Ml/min/1.73m^2
Number Analyzed 15225 participants 15224 participants 30449 participants
83  (17) 83  (17) 83  (17)
1.Primary Outcome
Title Number of Participants With Major Coronary Event
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anacetrapib Placebo Anacetrapib
Hide Arm/Group Description:
Anacetrapib: 100mg tablet daily
Placebo anacetrapib: 1 tablet daily
Overall Number of Participants Analyzed 15225 15224
Measure Type: Count of Participants
Unit of Measure: Participants
1640
  10.8%
1803
  11.8%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib, Placebo Anacetrapib
Comments [Not Specified]
Type of Statistical Test Other
Comments Time to first event
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.85 to 0.97
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Number of Participants With Major Atherosclerotic Event
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anacetrapib Placebo Anacetrapib
Hide Arm/Group Description:
Anacetrapib: 100mg daily
Placebo anacetrapib: 1 tablet daily
Overall Number of Participants Analyzed 15225 15224
Measure Type: Count of Participants
Unit of Measure: Participants
1383
   9.1%
1483
   9.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib, Placebo Anacetrapib
Comments [Not Specified]
Type of Statistical Test Other
Comments Time to first event
Statistical Test of Hypothesis P-Value 0.052
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.86 to 1
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants With Presumed Ischaemic Stroke
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anacetrapib Placebo Anacetrapib
Hide Arm/Group Description:
Anacetrapib: 100mg tablet daily
Placebo anacetrapib: 1 tablet daily
Overall Number of Participants Analyzed 15225 15224
Measure Type: Count of Participants
Unit of Measure: Participants
485
   3.2%
489
   3.2%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib, Placebo Anacetrapib
Comments [Not Specified]
Type of Statistical Test Other
Comments Time to first event
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.87 to 1.12
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Number of Participants With Major Vascular Event
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Anacetrapib Placebo Anacetrapib
Hide Arm/Group Description:
Anacetrapib: 100mg daily
Placebo anacetrapib: 1 tablet daily
Overall Number of Participants Analyzed 15225 15224
Measure Type: Count of Participants
Unit of Measure: Participants
2068
  13.6%
2214
  14.5%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Anacetrapib, Placebo Anacetrapib
Comments [Not Specified]
Type of Statistical Test Other
Comments Time to first event
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.88 to 0.99
Estimation Comments [Not Specified]
Time Frame Randomized treatment phase during median follow-up period of 4.1years
Adverse Event Reporting Description All participants were assessed for adverse events at 6-monthly intervals at which relevant information was recorded on the electronic case report form. In accordance with the protocol, Serious Adverse Events were recorded for all participants (30,449 subjects) and non-serious Adverse Events (presented in the ‘Other Adverse Events’ section) were recorded in North America only (6,082 subjects).
 
Arm/Group Title Anacetrapib Placebo Anacetrapib
Hide Arm/Group Description anacetrapib: tablet, 100mg daily placebo anacetrapib: tablet, 1 tablet daily
All-Cause Mortality
Anacetrapib Placebo Anacetrapib
Affected / at Risk (%) Affected / at Risk (%)
Total   1122/15225 (7.37%)      1155/15224 (7.59%)    
Show Serious Adverse Events Hide Serious Adverse Events
Anacetrapib Placebo Anacetrapib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8898/15225 (58.44%)      8912/15224 (58.54%)    
Blood and lymphatic system disorders     
Blood and lymphatic system disorders  1  188/15225 (1.23%)  219 182/15224 (1.20%)  210
Cardiac disorders     
Cardiac disorders  1  2568/15225 (16.87%)  4120 2766/15224 (18.17%)  4280
Congenital, familial and genetic disorders     
Congenital, familial and genetic disorders  1  9/15225 (0.06%)  9 4/15224 (0.03%)  4
Ear and labyrinth disorders     
Ear and labyrinth disorders  1  114/15225 (0.75%)  121 91/15224 (0.60%)  99
Endocrine disorders     
Endocrine disorders  1  50/15225 (0.33%)  50 49/15224 (0.32%)  51
Eye disorders     
Eye disorders  1  204/15225 (1.34%)  235 232/15224 (1.52%)  264
Gastrointestinal disorders     
Gastrointestinal disorders  1  813/15225 (5.34%)  1012 788/15224 (5.18%)  976
General disorders     
General disorders & administration site conditions  1  691/15225 (4.54%)  781 736/15224 (4.83%)  838
Hepatobiliary disorders     
Hepatobiliary disorders  1  217/15225 (1.43%)  251 238/15224 (1.56%)  268
Immune system disorders     
Immune system disorders  1  12/15225 (0.08%)  12 29/15224 (0.19%)  29
Infections and infestations     
Infections and infestations  1  1559/15225 (10.24%)  2097 1537/15224 (10.10%)  2152
Injury, poisoning and procedural complications     
Injury, poisoning and procedural complications  1  753/15225 (4.95%)  889 777/15224 (5.10%)  918
Investigations     
Investigations  1  1105/15225 (7.26%)  1421 1135/15224 (7.46%)  1419
Metabolism and nutrition disorders     
Metabolism and nutrition disorders  1  642/15225 (4.22%)  774 687/15224 (4.51%)  820
Musculoskeletal and connective tissue disorders     
Musculoskeletal and connective tissue disorders  1  438/15225 (2.88%)  508 432/15224 (2.84%)  501
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Neoplasms benign, malignant and unspecified (incl cycts and polyps)  1  1323/15225 (8.69%)  1810 1295/15224 (8.51%)  1770
Nervous system disorders     
Nervous system disorders  1  1399/15225 (9.19%)  1789 1455/15224 (9.56%)  1822
Psychiatric disorders     
Psychiatric disorders  1  104/15225 (0.68%)  117 111/15224 (0.73%)  124
Renal and urinary disorders     
Renal and urinary disorders  1  415/15225 (2.73%)  516 398/15224 (2.61%)  470
Reproductive system and breast disorders     
Reproductive system and breast disorders  1  49/15225 (0.32%)  53 56/15224 (0.37%)  59
Respiratory, thoracic and mediastinal disorders     
Respiratory, thoracic and mediastinal disorders  1  606/15225 (3.98%)  791 605/15224 (3.97%)  813
Skin and subcutaneous tissue disorders     
Skin and subcutaneous tissue disorders  1  84/15225 (0.55%)  93 97/15224 (0.64%)  109
Social circumstances     
Social circumstances  1  501/15225 (3.29%)  769 516/15224 (3.39%)  778
Surgical and medical procedures     
Surgical and medical procedures  1  3409/15225 (22.39%)  5051 3478/15224 (22.85%)  5241
Vascular disorders     
Vascular disorders  1  346/15225 (2.27%)  399 352/15224 (2.31%)  393
1
Term from vocabulary, MedDRA (14.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Anacetrapib Placebo Anacetrapib
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2493/3048 (81.79%)      2503/3034 (82.50%)    
Cardiac disorders     
Cardiac disorders  1  169/3048 (5.54%)  208/3034 (6.86%) 
Eye disorders     
Eye disorders  1  227/3048 (7.45%)  230/3034 (7.58%) 
Gastrointestinal disorders     
Gastrointestinal disorders  1  596/3048 (19.55%)  557/3034 (18.36%) 
General disorders     
General disorders and administration site conditions  1  321/3048 (10.53%)  338/3034 (11.14%) 
Infections and infestations     
Infections and infestations  1  974/3048 (31.96%)  943/3034 (31.08%) 
Injury, poisoning and procedural complications     
Injury, poisoning and procedural complications  1  480/3048 (15.75%)  516/3034 (17.01%) 
Investigations     
Investigations  1  327/3048 (10.73%)  307/3034 (10.12%) 
Metabolism and nutrition disorders     
Metabolism and nutrition disorders  1  405/3048 (13.29%)  393/3034 (12.95%) 
Musculoskeletal and connective tissue disorders     
Musculoskeletal and connective tissue disorders  1  1125/3048 (36.91%)  1105/3034 (36.42%) 
Nervous system disorders     
Nervous system disorders  1  625/3048 (20.51%)  623/3034 (20.53%) 
Psychiatric disorders     
Psychiatric disorders  1  155/3048 (5.09%)  139/3034 (4.58%) 
Renal and urinary disorders     
Renal and urinary disorders  1  160/3048 (5.25%)  171/3034 (5.64%) 
Respiratory, thoracic and mediastinal disorders     
Respiratory, thoracic and mediastinal disorders  1  463/3048 (15.19%)  412/3034 (13.58%) 
Skin and subcutaneous tissue disorders     
Skin and subcutaneous tissue disorders  1  203/3048 (6.66%)  211/3034 (6.95%) 
Surgical and medical procedures     
Surgical and medical procedures  1  211/3048 (6.92%)  202/3034 (6.66%) 
Vascular disorders     
Vascular disorders  1  185/3048 (6.07%)  189/3034 (6.23%) 
1
Term from vocabulary, MedDRA (14.0)
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Prof Martin Landray
Organization: Nuffield Department of Population Health, University of Oxford
Phone: +44 (0)1865 743743
EMail: martin.landray@ndph.ox.ac.uk
Layout table for additonal information
Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT01252953     History of Changes
Other Study ID Numbers: CTSUREVEAL1
48678192 ( Registry Identifier: ISRCTN )
2010-023467-18 ( EudraCT Number )
First Submitted: November 24, 2010
First Posted: December 3, 2010
Results First Submitted: February 1, 2018
Results First Posted: May 4, 2018
Last Update Posted: March 18, 2019