Efficacy of Pamidronate in the Treatment of Bone Loss Associated With Liver Transplant

Bone Disease, Metabolic Clinical Trial

Official title:

Prospective, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy of Disodium Pamidronate in the Treatment of Bone Loss Associated With Liver Transplant

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00657852
• Other study ID #: 99-NV001
• Status: Completed
• Phase: Phase 4
• First received: April 8, 2008
• Last updated: April 8, 2008
• Start date: December 2000
• Est. completion date: December 2003

Study information

• Verified date: April 2008
• Source: Hospital Clinic of Barcelona
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial Summary

The aims of this study are to prospectively evaluate the efficacy of two intravenous infusions of pamidronate 90 mg, associated with calcium and calcidiol, in the early post-transplant period, on bone loss in liver transplant recipients, and to asses the safety of this treatment.

Description:

Patients diagnosed with chronic advanced liver disease awaiting orthotopic liver transplantation will be eligible to take part in this study.

Patients excluded from the study will be those younger than 18 years, those receiving a multiorgan transplant or retransplant, or patients with a previous allergy to bisphosphonates. Previous treatment with fluoride, estrogens, selective estrogen receptor modulators or bisphosphonates will be another reason for exclusion, as well as therapy with glucocorticoids during the last 6 months before transplantation. None of the patients will have a previous history of disorders, other than liver disease, known to affect bone metabolism.

Study Design and Conduct

The study will be a 1-year prospective, randomized, double-blind, placebo-controlled trial conducted at 10 centers in Spain.

Immunosuppression

All patients will receive microemulsion cyclosporine A (CsA) as primary immunosuppressive agent, in combination with glucocorticoids. Additionally, mycophenolate mofetil will be associated according to the usual clinical practice of each center. In all cases, glucocorticoids will be progressively tapered during the first year.

Intervention

Patients will receive oral calcium (500 mg twice daily) and oral 25-hydroxy vitamin D (16000 UI every 15 days), after informed consent for the study will be obtained and exploratory screening will be done. Within days 7-12 after engraftment, the recruited transplanted patients (will be randomized to either the experimental or placebo group. Patients of the treatment group will receive a single dose of 90 mg disodium pamidronate within days 7-12 and at 3 months after liver transplantation, diluted in 500 ml of 5% glucose serum and administered as a 4-hour continuous intravenous infusion. Patients of the placebo group will receive 500 ml of 5% glucoside serum infusions. Treatment with oral calcium and vitamin D will be maintained for 1 year after transplantation.

Study Endpoints

The primary endpoints of the study will be changes in bone mineral density (BMD), quantified by dual energy X-ray absorptiometry (DXA) and safety of pamidronate by recording adverse events. Secondary endpoints will include the incidence of skeletal fractures, by assessment of radiological vertebral fractures (symptomatic and asymptomatic), and the development of nonvertebral fractures.

Evaluation

Five study visits will be scheduled: before transplantation, within day 7-12 after liver transplantation and at 3, 6 and 12 months after liver transplantation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: December 2003
• Est. primary completion date: December 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• diagnosed with chronic advanced liver disease awaiting orthotopic liver transplantation

Exclusion Criteria:

• younger than 18 years

• receiving a multiorgan transplant or retransplant

• previous allergy to bisphosphonates

• Previous treatment with fluoride, estrogens, selective estrogen receptor modulators or bisphosphonates

• therapy with glucocorticoids during the last 6 months before transplantation

• previous history of disorders, other than liver disease, known to affect bone metabolism.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bone Disease, Metabolic
• Bone Diseases
• Bone Diseases, Metabolic
• Metabolic Diseases

Intervention

Drug:
• Disodium pamidronate
Single dose of 90 mg disodium pamidronate within days 7-12 and at 3 months after liver transplantation, diluted in 500 ml of 5% glucose serum and administered as a 4-hour continuous intravenous infusion
• Placebo
500 ml of 5% glucoside serum infusions within days 7-12 and at 3 months after liver transplantation and administered as a 4-hour continuous intravenous infusion

Locations

Country	Name	City	State
Spain	Hospital Clinic i Provincial of Barcelona	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
Hospital Clinic of Barcelona	Novartis

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	bone mineral density (BMD), quantified by dual energy X-ray absorptiometry (DXA)		Change during the 1-year of follow up	No
Secondary	adverse events		incidence during 1-year of follow-up	Yes
Secondary	incidence of skeletal fractures, by assessment of radiological vertebral fractures (symptomatic and asymptomatic),		1-year of follow-up	No
Secondary	incidence of nonvertebral fractures		1-year follow-up	No