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Zoledronic Acid Versus Alendronate for Prevention of Bone Loss After Organ Transplantation (CTX)

This study has been completed.
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Elizabeth Shane, Columbia University
ClinicalTrials.gov Identifier:
NCT00297830
First received: February 27, 2006
Last updated: July 28, 2016
Last verified: July 2016
Results First Received: February 15, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Prevention
Conditions: Heart Transplantation
Liver Transplantation
Bone Resorption
Interventions: Drug: Zoledronic acid
Drug: Alendronate
Other: Placebo Zoledronic Acid
Other: Placebo Alendronate

  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
Men and women, aged 20 to 70 yr, who had undergone heart or liver transplantation at CUMC were eligible. Of 495 patients transplanted between 3/2006 and 7/2009, 235 were ineligible. 149 patients declined or were not approached. 84 were randomized, 43 to alendronate and 41 to zoledronate. 27 were the reference group since they refused randomization.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Serum creatinine levels above 2.0 mg/dl, or enrollment in another clinical trial

Reporting Groups
  Description
Active Zoledronic Acid and Placebo Alendronate Group 1 will receive an infusion of active zoledronic acid 5 mg during the first 4 weeks after transplantation. Placebo alendronate 70 mg once weekly will be initiated at the same time as the first zoledronic acid infusion.
Placebo Zoledronic Acid and Active Alendronate Group 2 will receive an infusion of placebo during the first 5 weeks after transplantation. Active alendronate 70 mg once weekly will be initiated at the same time as the placebo infusion.
Reference Group The reference group included concurrently transplanted patients with T scores of -1.5 or greater.

Participant Flow for 3 periods

Period 1:   Baseline
    Active Zoledronic Acid and Placebo Alendronate     Placebo Zoledronic Acid and Active Alendronate     Reference Group  
STARTED     41     43     27  
COMPLETED     41     43     27  
NOT COMPLETED     0     0     0  

Period 2:   6 Month Visit
    Active Zoledronic Acid and Placebo Alendronate     Placebo Zoledronic Acid and Active Alendronate     Reference Group  
STARTED     41     43     27  
COMPLETED     38     41     24  
NOT COMPLETED     3     2     3  
Death                 1                 0                 2  
Withdrawal by Subject                 2                 1                 1  
Adverse Event                 0                 1                 0  

Period 3:   12 Month Visit
    Active Zoledronic Acid and Placebo Alendronate     Placebo Zoledronic Acid and Active Alendronate     Reference Group  
STARTED     38     41     24  
COMPLETED     37     35     24  
NOT COMPLETED     1     6     0  
Lost to Follow-up                 1                 0                 0  
Adverse Event                 0                 3                 0  
Withdrawal by Subject                 0                 3                 0  



  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.
Based on preliminary data that total hip BMD would decrease by 1.5 ± 3.7% on alendronate and increase by 1.0 ± 3.7% on zoledronate, we estimated that 35 subjects per group would provide 80% power and 5% α to detect a 2.5 ± 3.7% difference between randomized groups. Anticipating a 20% dropout, 84 subjects were randomized.

Reporting Groups
  Description
Active Zoledronic Acid and Placebo Alendronate Group 1 will receive an infusion of active zoledronic acid 5 mg during the first 4 weeks after transplantation. Placebo alendronate 70 mg once weekly will be initiated at the same time as the first zoledronic acid infusion.
Placebo Infusion and Active Alendronate Group 2 will receive an infusion of placebo during the first 5 weeks after transplantation. Active alendronate 70 mg once weekly will be initiated at the same time as the placebo infusion.
Reference Group The reference group included concurrently transplanted patients with T scores of -1.5 or greater.
Total Total of all reporting groups

Baseline Measures
    Active Zoledronic Acid and Placebo Alendronate     Placebo Infusion and Active Alendronate     Reference Group     Total  
Number of Participants  
[units: participants]
  41     43     27     111  
Age  
[units: years]
Mean (Standard Deviation)
  55  (8)     54  (10)     48  (15)     52.9  (11.1)  
Gender  
[units: participants]
       
Female     11     8     7     26  
Male     30     35     20     85  
Ethnicity (NIH/OMB)  
[units: participants]
       
Hispanic or Latino     4     12     5     21  
Not Hispanic or Latino     37     31     22     90  
Unknown or Not Reported     0     0     0     0  



  Outcome Measures
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1.  Primary:   Percentage Change From Baseline in Total Hip Bone Mineral Density (BMD) at 12 Months   [ Time Frame: Baseline, 12 months ]

2.  Secondary:   Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months   [ Time Frame: Baseline, 12 months ]

3.  Secondary:   Percentage Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at 12 Months   [ Time Frame: Baseline, 12 months ]

4.  Secondary:   Serum N-telopeplide Percent Change   [ Time Frame: 24 months ]


  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
Heart and liver transplant recipients differ in pretransplant bone disease and exposure to prednisone. Not powered to detect differences in fracture rates,an important clinical outcome,one that would require a large comparative effectiveness trial.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Dr. Elizabeth Shane
Organization: Columbia University
phone: 2123056289
e-mail: es54@columbia.edu


Publications of Results:
Other Publications:

Responsible Party: Elizabeth Shane, Columbia University
ClinicalTrials.gov Identifier: NCT00297830     History of Changes
Other Study ID Numbers: AAAB2324
CZOL446H104 ( Other Identifier: Novartis )
Study First Received: February 27, 2006
Results First Received: February 15, 2013
Last Updated: July 28, 2016
Health Authority: United States: Institutional Review Board