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

This study has been completed.
Sponsor:
Collaborator:
Novartis
Information provided by:
Hospital Clinic of Barcelona
ClinicalTrials.gov Identifier:
NCT00657852
First received: April 8, 2008
Last updated: NA
Last verified: April 2008
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Bone Disease, Metabolic
Drug: Disodium pamidronate
Drug: Placebo
Phase 4

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

Resource links provided by NLM:


Further study details as provided by Hospital Clinic of Barcelona:

Primary Outcome Measures:
  • bone mineral density (BMD), quantified by dual energy X-ray absorptiometry (DXA) [ Time Frame: Change during the 1-year of follow up ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • adverse events [ Time Frame: incidence during 1-year of follow-up ] [ Designated as safety issue: Yes ]
  • incidence of skeletal fractures, by assessment of radiological vertebral fractures (symptomatic and asymptomatic), [ Time Frame: 1-year of follow-up ] [ Designated as safety issue: No ]
  • incidence of nonvertebral fractures [ Time Frame: 1-year follow-up ] [ Designated as safety issue: No ]

Enrollment: 79
Study Start Date: December 2000
Study Completion Date: December 2003
Primary Completion Date: December 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
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
Other Name: Aredia
Placebo Comparator: 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
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00657852

Locations
Spain
Hospital Clinic i Provincial of Barcelona
Barcelona, Spain, 08036
Sponsors and Collaborators
Hospital Clinic of Barcelona
Novartis
Investigators
Principal Investigator: Miquel Navasa, Dr Hospital Clinic i Provincial, Barcelona
  More Information

No publications provided

Responsible Party: Dr. Miquel Navasa Anadón, Digestive Diseases Institute, Hospital Clinic of Barcelona
ClinicalTrials.gov Identifier: NCT00657852     History of Changes
Other Study ID Numbers: 99-NV001
Study First Received: April 8, 2008
Last Updated: April 8, 2008
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Hospital Clinic of Barcelona:
pamidronate,bone loss, liver transplantation

Additional relevant MeSH terms:
Bone Diseases
Bone Diseases, Metabolic
Metabolic Diseases
Musculoskeletal Diseases
Pamidronate
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 20, 2014