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

NCT ID: NCT00657852

Last Updated: 2008-04-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 79 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-12-31
• Study Completion Date: 2003-12-31

Brief 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.

Detailed 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.

Conditions

Bone Disease, Metabolic

Keywords

pamidronate,bone loss, liver transplantation

Study Design

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

Study Groups

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

Group Type: EXPERIMENTAL

Disodium pamidronate

Intervention Type: DRUG

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

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

Intervention Type: DRUG

Other Intervention Names

Aredia

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

Hospital Clinic of Barcelona

OTHER

Sponsor Role: lead

Responsible Party

Digestive Diseases Institute, Hospital Clinic of Barcelona

Principal Investigators

Miquel Navasa, Dr

Role: PRINCIPAL_INVESTIGATOR

Hospital Clinic i Provincial, Barcelona

Locations

Hospital Clinic i Provincial of Barcelona

Barcelona, Barcelona, Spain

Countries

Spain

Other Identifiers

99-NV001

Identifier Type: -

Identifier Source: org_study_id