E.V.O.L.V.E. Trial™: EValuation Of Cinacalcet Hydrochloride (HCl) Therapy to Lower CardioVascular Events (EVOLVE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00345839
First received: June 27, 2006
Last updated: July 11, 2014
Last verified: July 2014
Results First Received: June 6, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Conditions: Secondary Hyperparathyroidism
Chronic Kidney Disease
Interventions: Drug: Cinacalcet
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were recruited from dialysis clinics and hospitals between August 2006 to Jan 2008 from 22 countries.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were screened over a 30 day period.

Reporting Groups
  Description
Cinacalcet Cinacalcet administered orally in doses of 30, 60, 90, 120 or 180 mg per day. Participants could be titrated up to maximum dose based on PTH (parathyroid hormone), serum calcium and safety assessments.
Placebo Participants were given matching placebo tablets compared to the cinacalcet group.

Participant Flow:   Overall Study
    Cinacalcet     Placebo  
STARTED     1948 [1]   1935 [2]
COMPLETED     1799 [3]   1776 [3]
NOT COMPLETED     149     159  
Withdrawal by Subject                 91                 98  
Lost to Follow-up                 58                 61  
[1] Randomized to cinacalcet
[2] Randomized to placebo
[3] Participants who completed study includes those with ended study due to death.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Cinacalcet Cinacalcet administered orally in doses of 30, 60, 90, 120 or 180 mg per day. Participants could be titrated up to maximum dose based on PTH (parathyroid hormone), serum calcium and safety assessments.
Placebo Participants were given matching placebo tablets compared to the cinacalcet group.
Total Total of all reporting groups

Baseline Measures
    Cinacalcet     Placebo     Total  
Number of Participants  
[units: participants]
  1948     1935     3883  
Age  
[units: Years]
Mean ± Standard Deviation
  54.8  ± 14.5     54.0  ± 14.2     54.4  ± 14.4  
Gender  
[units: Participants]
     
Female     809     769     1578  
Male     1139     1166     2305  
Race/Ethnicity, Customized  
[units: Participants]
     
White or Caucasian     1124     1116     2240  
Black or African American     409     428     837  
Hispanic or Latino     317     310     627  
Asian     47     38     85  
Japanese     4     1     5  
American Indian or Alaska Native     5     7     12  
Native Hawaiian or Other Pacific Islander     12     9     21  
Aborigine     1     4     5  
Other     29     22     51  
History of Diabetes Stratification Factor [1]
[units: Participants]
     
Diabetes     619     614     1233  
No Diabetes     1329     1321     2650  
Country stratification factor [2]
[units: Participants]
     
Argentina     171     170     341  
Australia     74     75     149  
Austria     31     29     60  
Belgium     50     50     100  
Brazil     151     150     301  
Canada     73     73     146  
Denmark     8     11     19  
France     40     40     80  
Germany     81     81     162  
Hungary     66     67     133  
Ireland     5     6     11  
Italy     69     68     137  
Mexico     23     22     45  
Netherlands     15     14     29  
Poland     59     57     116  
Portugal     22     21     43  
Russia     143     140     283  
Spain     40     38     78  
Sweden     13     10     23  
Switzerland     18     19     37  
United Kingdom     81     79     160  
United States     715     715     1430  
[1] History of diabetes stratification factor from the interactive voice response system.
[2] Country stratification factor from the interactive voice response system. Denmark and Sweden were combined to create Nordic stratum.



  Outcome Measures
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1.  Primary:   Time to Primary Composite Endpoint (All-cause Mortality, Myocardial Infarction, Hospitalization for Unstable Angina, Heart Failure or Peripheral Vascular Event)   [ Time Frame: From date of randomization until date of first confirmed primary composite endpoint event, assessed up to 5.4 years ]

2.  Secondary:   Time to All-cause Mortality   [ Time Frame: From date of randomization until date of confirmed all-cause mortality endpoint event, assessed up to 5.4 years ]

3.  Secondary:   Time to Myocardial Infarction   [ Time Frame: From date of randomization until date of first confirmed myocardial infarction endpoint event, assessed up to 5.4 years ]

4.  Secondary:   Time to Hospitalization for Unstable Angina   [ Time Frame: From date of randomization until date of first confirmed hospitalization for unstable angina endpoint event, assessed up to 5.4 years ]

5.  Secondary:   Time to Heart Failure   [ Time Frame: From date of randomization until date of first confirmed heart failure endpoint event, assessed up to 5.4 years ]

6.  Secondary:   Time to Peripheral Vascular Event   [ Time Frame: From date of randomization until date of first confirmed peripheral vascular endpoint event, assessed up to 5.4 years ]

7.  Secondary:   Time to Cardiovascular Mortality   [ Time Frame: From date of randomization until date of first confirmed cardiovascular mortality endpoint event, assessed up to 5.4 years ]

8.  Secondary:   Time to Stroke   [ Time Frame: From date of randomization until date of first confirmed stroke endpoint event, assessed up to 5.4 years ]

9.  Secondary:   Time to Bone Fracture   [ Time Frame: From date of randomization until date of first confirmed bone fracture endpoint event, assessed up to 5.4 years ]
  Hide Outcome Measure 9

Measure Type Secondary
Measure Title Time to Bone Fracture
Measure Description Time to Bone Fracture. Stratified by history of diabetes and country.
Time Frame From date of randomization until date of first confirmed bone fracture endpoint event, assessed up to 5.4 years  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Utilizes the Efficacy Analysis Set which includes all randomized participants. Participants were analyzed in the treatment group as randomized using the Intent-to-treat (ITT) method.

Reporting Groups
  Description
Cinacalcet Cinacalcet administered orally in doses of 30, 60, 90, 120 or 180 mg per day. Participants could be titrated up to maximum dose based on PTH (parathyroid hormone), serum calcium and safety assessments.
Placebo Participants were given matching placebo tablets compared to the cinacalcet group.

Measured Values
    Cinacalcet     Placebo  
Number of Participants Analyzed  
[units: participants]
  1948     1935  
Time to Bone Fracture  
[units: Months]
Median ( Inter-Quartile Range )
  NA  
  ( NA to NA ) [1]
  NA  
  ( NA to NA ) [1]
[1] NA (Not Applicable) indicates that the parameter is not estimable due to insufficient number of subjects with events.


Statistical Analysis 1 for Time to Bone Fracture
Groups [1] All groups
Method [2] Log Rank
P Value [3] 0.218
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Stratified by history of diabetes and country. 2-sided test.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No adjustments for multiple comparisons were made for this endpoint.

Statistical Analysis 2 for Time to Bone Fracture
Groups [1] All groups
Method [2] Regression, Cox
Hazard Ratio (HR) [3] 0.89
95% Confidence Interval ( 0.75 to 1.07 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Stratified by history of diabetes and country.
[3] Other relevant estimation information:
  HR is cinacalcet vs placebo.



10.  Secondary:   Time to Parathyroidectomy   [ Time Frame: From date of randomization until date of first confirmed parathyroidectomy endpoint event, assessed up to 5.4 years ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


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