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 ]

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
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Time Frame Average 24 months
Additional Description The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. The number of participants at risk includes subjects who received at least 1 dose of investigational product.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

Reporting Groups
  Description
Placebo No text entered.
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.

Other Adverse Events
    Placebo     Cinacalcet  
Total, other (not including serious) adverse events      
# participants affected / at risk     1220/1923     1444/1938  
Blood and lymphatic system disorders      
Anaemia † 1    
# participants affected / at risk     96/1923 (4.99%)     109/1938 (5.62%)  
Gastrointestinal disorders      
Abdominal pain † 1    
# participants affected / at risk     154/1923 (8.01%)     187/1938 (9.65%)  
Abdominal pain upper † 1    
# participants affected / at risk     121/1923 (6.29%)     153/1938 (7.89%)  
Diarrhoea † 1    
# participants affected / at risk     349/1923 (18.15%)     376/1938 (19.40%)  
Dyspepsia † 1    
# participants affected / at risk     89/1923 (4.63%)     140/1938 (7.22%)  
Nausea † 1    
# participants affected / at risk     288/1923 (14.98%)     552/1938 (28.48%)  
Vomiting † 1    
# participants affected / at risk     247/1923 (12.84%)     482/1938 (24.87%)  
General disorders      
Chest pain † 1    
# participants affected / at risk     119/1923 (6.19%)     134/1938 (6.91%)  
Oedema peripheral † 1    
# participants affected / at risk     96/1923 (4.99%)     117/1938 (6.04%)  
Pyrexia † 1    
# participants affected / at risk     161/1923 (8.37%)     126/1938 (6.50%)  
Infections and infestations      
Bronchitis † 1    
# participants affected / at risk     121/1923 (6.29%)     138/1938 (7.12%)  
Nasopharyngitis † 1    
# participants affected / at risk     138/1923 (7.18%)     157/1938 (8.10%)  
Upper respiratory tract infection † 1    
# participants affected / at risk     119/1923 (6.19%)     144/1938 (7.43%)  
Urinary tract infection † 1    
# participants affected / at risk     94/1923 (4.89%)     114/1938 (5.88%)  
Injury, poisoning and procedural complications      
Arteriovenous fistula site complication † 1    
# participants affected / at risk     107/1923 (5.56%)     124/1938 (6.40%)  
Metabolism and nutrition disorders      
Decreased appetite † 1    
# participants affected / at risk     67/1923 (3.48%)     112/1938 (5.78%)  
Hypocalcaemia † 1    
# participants affected / at risk     20/1923 (1.04%)     206/1938 (10.63%)  
Musculoskeletal and connective tissue disorders      
Arthralgia † 1    
# participants affected / at risk     224/1923 (11.65%)     158/1938 (8.15%)  
Back pain † 1    
# participants affected / at risk     146/1923 (7.59%)     159/1938 (8.20%)  
Muscle spasms † 1    
# participants affected / at risk     174/1923 (9.05%)     213/1938 (10.99%)  
Musculoskeletal pain † 1    
# participants affected / at risk     125/1923 (6.50%)     109/1938 (5.62%)  
Pain in extremity † 1    
# participants affected / at risk     193/1923 (10.04%)     201/1938 (10.37%)  
Nervous system disorders      
Dizziness † 1    
# participants affected / at risk     86/1923 (4.47%)     135/1938 (6.97%)  
Headache † 1    
# participants affected / at risk     182/1923 (9.46%)     219/1938 (11.30%)  
Respiratory, thoracic and mediastinal disorders      
Cough † 1    
# participants affected / at risk     185/1923 (9.62%)     225/1938 (11.61%)  
Dyspnoea † 1    
# participants affected / at risk     188/1923 (9.78%)     226/1938 (11.66%)  
Skin and subcutaneous tissue disorders      
Pruritus † 1    
# participants affected / at risk     107/1923 (5.56%)     103/1938 (5.31%)  
Vascular disorders      
Hypertension † 1    
# participants affected / at risk     160/1923 (8.32%)     176/1938 (9.08%)  
Hypotension † 1    
# participants affected / at risk     154/1923 (8.01%)     183/1938 (9.44%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 15.0



  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
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