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| ID | Type | Description | Link |
|---|---|---|---|
| CZOL446H104 | Other Identifier | Novartis |
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| Name | Class |
|---|---|
| Novartis Pharmaceuticals | INDUSTRY |
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The purpose of this study is to compare the effectiveness and safety of zoledronic acid with alendronate in the prevention of bone loss after organ transplantation. Zoledronic acid is given as a single intravenous infusion. Alendronate is given as a weekly pill. Both are expected to be very effective, but it is not known which one will work best.
Patients who have undergone heart or liver transplantation are usually required to remain on medications, such as Prednisone and Cyclosporine A or Tacrolimus, that prevent the body from rejecting the transplanted organ. These medications may cause bone loss which leads to thinning of the bones (osteoporosis) and therefore greatly increase the risk of having broken bones (fractures) after transplantation. Several published studies have shown that 14% to 35% of heart transplant patients develop fractures (spine, ribs and hip) during the first year after transplantation. We have previously shown that alendronate (Fosamax), a drug approved by the FDA for prevention and treatment of postmenopausal osteoporosis and prednisone-induced osteoporosis, prevents bone loss after heart transplantation. We are conducting this study to determine whether a newer drug, zoledronic acid, is as effective as alendronate.
This study is a randomized, double-blind, placebo-controlled 2-year study. Participants will receive one dose of active zoledronic acid during the first month after heart or liver transplantation and weekly placebo alendronate pills or one dose of placebo zoledronic acid and weekly active alendronate pills for the first year after transplant. Over 2 years, participants will provide blood samples on nine occasions. Bone density will be performed 4-5 times and spine xrays will be performed twice.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active Zoledronic Acid & Placebo Alendronate | Experimental | 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. |
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| Placebo Zoledronic Acid & Active Alendronate | Experimental | Group 2 will receive an infusion of placebo zoledronic acid during the first 5 weeks after transplantation. Active alendronate 70 mg once weekly will be initiated at the same time as the placebo infusion. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Zoledronic acid | Drug | Drug is administered through 5 mg intravenous infusion over 20 minutes |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage Change From Baseline in Total Hip Bone Mineral Density (BMD) at 12 Months | BMD was measured by dual-energy x-ray absorptiometry (QDR-4500 densitometer; Hologic, Inc., Bedford, MA); short-term in vivo coefficient of variation is 0.68% (spine) and 1.36% (femoral neck). T scores were generated using gender-specific databases provided by the manufacturer. | Baseline, 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months | BMD was measured by dual-energy x-ray absorptiometry (QDR-4500 densitometer; Hologic, Inc., Bedford, MA); short-term in vivo coefficient of variation is 0.68% (spine) and 1.36% (femoral neck). T scores were generated using gender-specific databases provided by the manufacturer. | Baseline, 12 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Elizabeth Shane, M.D. | Columbia University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Columbia University Medical Center | New York | New York | 10032 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 14973216 | Background | Shane E, Addesso V, Namerow PB, McMahon DJ, Lo SH, Staron RB, Zucker M, Pardi S, Maybaum S, Mancini D. Alendronate versus calcitriol for the prevention of bone loss after cardiac transplantation. N Engl J Med. 2004 Feb 19;350(8):767-76. doi: 10.1056/NEJMoa035617. | |
| 23024190 | Result | Shane E, Cohen A, Stein EM, McMahon DJ, Zhang C, Young P, Pandit K, Staron RB, Verna EC, Brown R, Restaino S, Mancini D. Zoledronic acid versus alendronate for the prevention of bone loss after heart or liver transplantation. J Clin Endocrinol Metab. 2012 Dec;97(12):4481-90. doi: 10.1210/jc.2012-2804. Epub 2012 Sep 28. |
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Serum creatinine levels above 2.0 mg/dl, or enrollment in another clinical trial
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | Reference Group | The reference group included concurrently transplanted patients with T scores of -1.5 or greater. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline |
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| 6 Month Visit |
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| 12 Month Visit |
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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.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Placebo Infusion and Active Alendronate |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage Change From Baseline in Total Hip Bone Mineral Density (BMD) at 12 Months | BMD was measured by dual-energy x-ray absorptiometry (QDR-4500 densitometer; Hologic, Inc., Bedford, MA); short-term in vivo coefficient of variation is 0.68% (spine) and 1.36% (femoral neck). T scores were generated using gender-specific databases provided by the manufacturer. | Posted | Mean | 95% Confidence Interval | percent change | Baseline, 12 months |
|
1 year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Death | General disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infection | Infections and infestations | Non-systematic Assessment | Includes all infections due to cytomegalovirus and all other infections that necessitated hospitalization, intravenous antibiotic therapy, or both. |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Elizabeth Shane | Columbia University | 2123056289 | es54@columbia.edu |
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| ID | Term |
|---|---|
| D001862 | Bone Resorption |
| ID | Term |
|---|---|
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
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| ID | Term |
|---|---|
| D000077211 | Zoledronic Acid |
| D019386 | Alendronate |
| ID | Term |
|---|---|
| D004164 | Diphosphonates |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
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| Alendronate | Drug | Alendronate 70 mg will be taken once a week in the morning at least 30-60 minutes before first meal |
|
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| Placebo Zoledronic Acid | Other | Infusion of placebo zoledronic acid during the first 5 weeks after transplantation |
|
| Placebo Alendronate | Other | Placebo alendronate 70 mg once weekly |
|
| Percentage Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at 12 Months | BMD was measured by dual-energy x-ray absorptiometry (QDR-4500 densitometer; Hologic, Inc., Bedford, MA); short-term in vivo coefficient of variation is 0.68% (spine) and 1.36% (femoral neck). T scores were generated using gender-specific databases provided by the manufacturer. | Baseline, 12 months |
| Serum N-telopeplide Percent Change | 24 months |
| NOT COMPLETED |
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| NOT COMPLETED |
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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. |
| BG002 | Reference Group | The reference group included concurrently transplanted patients with T scores of -1.5 or greater. |
| BG003 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
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. |
| OG002 | Reference Group | The reference group included concurrently transplanted patients with T scores of -1.5 or greater. |
|
|
| Secondary | Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 12 Months | BMD was measured by dual-energy x-ray absorptiometry (QDR-4500 densitometer; Hologic, Inc., Bedford, MA); short-term in vivo coefficient of variation is 0.68% (spine) and 1.36% (femoral neck). T scores were generated using gender-specific databases provided by the manufacturer. | Posted | Mean | 95% Confidence Interval | percent change | Baseline, 12 months |
|
|
|
| Secondary | Percentage Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at 12 Months | BMD was measured by dual-energy x-ray absorptiometry (QDR-4500 densitometer; Hologic, Inc., Bedford, MA); short-term in vivo coefficient of variation is 0.68% (spine) and 1.36% (femoral neck). T scores were generated using gender-specific databases provided by the manufacturer. | Posted | Mean | 95% Confidence Interval | percent change | Baseline, 12 months |
|
|
|
| Secondary | Serum N-telopeplide Percent Change | Serum n-telopeplide percent change was not collected. | Posted | 24 months |
|
|
| 21 |
| 41 |
| 14 |
| 41 |
| EG001 | 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.https://register.clinicaltrials.gov/prs/html/results\_definitions.html#Result\_ParticipantFlow\_Period\_title | 14 | 43 | 11 | 43 |
| EG002 | Reference Group | The reference group included concurrently transplanted patients with T scores of -1.5 or greater. | 2 | 27 | 0 | 27 |
| Hospitalization | General disorders | Non-systematic Assessment | Includes all hospital readmissions after randomization or enrollment. |
|
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| Rejection | General disorders | Non-systematic Assessment | Rejection after month 1 necessitating change in immunosuppressive regimen |
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| Flu-like symptoms after zoledronate or matching placebo | General disorders | Non-systematic Assessment |
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| Hypocalcemia | Endocrine disorders | Non-systematic Assessment | Albumin-corrected serum calcium below 8.0 mg/dL. To convert values for serum calcium to millimoles per liter, multiply by 0.2495. |
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| Serum Calcium > 2.0 mg/dL | Endocrine disorders | Non-systematic Assessment | At any visit after randomization. To convert values for serum creatinine to millimoles per liter, multiply by 88.4. |
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| Atrial fibrillation | Cardiac disorders | Non-systematic Assessment |
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| Abdominal Pain | General disorders | Non-systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
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| D007093 |
| Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |