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

NCT ID: NCT00297830

Last Updated: 2018-08-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 111 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-30
• Study Completion Date: 2014-01-31

Brief Summary

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.

Detailed Description

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.

Conditions

Heart Transplantation; Liver Transplantation; Bone Resorption

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Active Zoledronic Acid & 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.

Group Type: EXPERIMENTAL

Zoledronic acid

Intervention Type: DRUG

Drug is administered through 5 mg intravenous infusion over 20 minutes

Placebo Alendronate

Intervention Type: OTHER

Placebo alendronate 70 mg once weekly

Placebo Zoledronic Acid & Active Alendronate

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.

Group Type: EXPERIMENTAL

Alendronate

Intervention Type: DRUG

Alendronate 70 mg will be taken once a week in the morning at least 30-60 minutes before first meal

Placebo Zoledronic Acid

Intervention Type: OTHER

Infusion of placebo zoledronic acid during the first 5 weeks after transplantation

Interventions

Zoledronic acid

Drug is administered through 5 mg intravenous infusion over 20 minutes

Intervention Type: DRUG

Alendronate

Alendronate 70 mg will be taken once a week in the morning at least 30-60 minutes before first meal

Intervention Type: DRUG

Placebo Zoledronic Acid

Infusion of placebo zoledronic acid during the first 5 weeks after transplantation

Intervention Type: OTHER

Placebo Alendronate

Placebo alendronate 70 mg once weekly

Intervention Type: OTHER

Other Intervention Names

Zometa; Fosamax

Eligibility Criteria

Inclusion Criteria

• A man or woman, aged 20 to 70, of any race who has had a heart or liver transplant

Exclusion Criteria

• hyperparathyroidism
• Paget's disease
• hyperthyroidism
• cancer
• severe kidney disease,
• intestinal disease
• active peptic ulcer disease
• current or past treatment for osteoporosis
• pregnancy or lactation
• severe oral/dental disease

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Elizabeth Shane

Professor of Medicine, Endocrinology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Elizabeth Shane, M.D.

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Columbia University Medical Center

New York, New York, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 14973216 (View on PubMed)

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.

Reference Type: RESULT

PMID: 23024190 (View on PubMed)

Other Identifiers

CZOL446H104

Identifier Type: OTHER

Identifier Source: secondary_id

AAAB2324

Identifier Type: -

Identifier Source: org_study_id