Ignite Creation Date:
2024-05-05 @ 11:43 AM
Last Modification Date:
2024-10-26 @ 9:12 AM
Study NCT ID:
NCT00114556
Status:
COMPLETED
Last Update Posted:
2006-05-09
First Post:
2005-06-15
Brief Title:
The Effect of Zoledronic Acid on Bone Density in Liver Transplant Patients
Sponsor:
Royal Prince Alfred Hospital Sydney Australia
Organization:
Royal Prince Alfred Hospital Sydney Australia
Study Overview
Official Title:
The Effect Of The Bisphosphonate Zoledronic Acid On Bone Density In Liver Transplant Patients - A Prospective Randomised Controlled Clinical Trial
Status:
COMPLETED
Status Verified Date:
2004-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Following liver transplantation rapid bone loss occurs particularly within the first 6 months post-transplant This may be associated with fractures most notable vertebral The ability to assess osteoporosis therapies in this system may provide useful information for osteoporosis management in general
Hypotheses
1 That treatment with the bisphosphonate zoledronate at the time of liver transplantation and at 1 month post-transplantation will prevent the early transplant-related bone loss measured by bone densitometry and biochemical bone markers at 3 months seen in patients who are not treated with a bisphosphonate
2 That continuing treatment with zoledronate at 3 monthly intervals for a total duration of 12 months will result in further improvements in bone density beyond that seen at 3 months
3 That calcium and vitamin D vit D supplementation of liver transplant patients does not prevent marked bone loss following transplantation
Hypotheses
1 That treatment with the bisphosphonate zoledronate at the time of liver transplantation and at 1 month post-transplantation will prevent the early transplant-related bone loss measured by bone densitometry and biochemical bone markers at 3 months seen in patients who are not treated with a bisphosphonate
2 That continuing treatment with zoledronate at 3 monthly intervals for a total duration of 12 months will result in further improvements in bone density beyond that seen at 3 months
3 That calcium and vitamin D vit D supplementation of liver transplant patients does not prevent marked bone loss following transplantation
Detailed Description:
This study is a prospective randomised double-blind placebo-controlled clinical trial in liver transplant patients comparing therapy with the bisphosphonate zoledronate to patients who do not receive bisphosphonate therapy All groups will receive calcium and vit D supplementation from the time patients are listed for transplantation and for 12 months post-transplantation Recruited subjects will be 17 years or older ie adult in terms of consent requirements
The study groups comprise
Group 1 Zoledronate plus calcium and vit D supplementation
Zoledronate 4 mg will be administered by intravenous infusion details below at baseline within 72 h of liver transplantation followed by zoledronate 4 mg infused as outlined below at 1 3 6 and 9 months post-transplantation PLUS calcium 600mg daily Caltrate one tablet and ergocalciferol 1000 IU daily Ostelin one capsule for 12 months post-transplantation
Group 2 Placebo plus calcium and vit D supplementation
Placebo will consist of 50 ml NSaline infused over 15 minutes as for the zoledronate regime PLUS calcium 600mg daily Caltrate one tablet and ergocalciferol 1000 IU daily Ostelin one capsule Patients with low vitamin D levels 60 nmolL and parathyroid hormone Pth levels above normal 65 should receive ergocalciferol 5000 U daily
ZoledronatePlacebo Infusion regime
Zoledronate 4 mg will be infused in 100 ml NSaline over 15 minutes in patients with a creatinine level 15 times the upper limit of the normal range ie 165 µmolL Patients with renal impairment as indicated by a serum creatinine level 15 x ULN will be discussed on an individual basis with the Medical Adviser of Novartis If zoledronate is to be given an extended infusion time may be used Renal toxicity has been reported with rapid infusions 5 min of 8 mg of zoledronate in patients with pre-existing renal failure Further pharmacokinetic studies in patients with renal failure are being undertaken by Novartis to clarify this area Zoledronate infusion should be freshly prepared and administered without delay
The Hospital Pharmacy will be responsible for providing the infusions zoledronate reconstituted in NSaline or NSaline alone appropriately masked for both Groups 1 and 2
Primary Outcome Measures
1 Bone Density at 3 months post-transplantation
Maximal loss of bone following transplantation is seen by 3 months Earlier data on bone loss in liver transplant patients from the RPAH unit demonstrated an average of 24 bone loss by 3 months post-transplantation Prevention of this effect should provide a precise and early measurement of the effect of zoledronate on transplant-related bone loss Bone density of the hip spine and total body will be measured by dual xray absorptiometry DEXA at baseline not more than 6 months prior to liver transplantation and 3 6 and 12 months following liver transplantation
Secondary Outcome Measures
1 Bone Density at 6 and 12 months post-transplantation
The BMD assessments at 6 and 12 months will assess further changes in bone density between the treated and control groups beyond those assessed at 3 months
2 Biochemical Markers of Bone Metabolism
Biochemical markers of bone formation osteocalcin and total and bone specific alkaline phosphatase and bone resorption urinary collagen cross-links N-teleopeptide and deoxypyridinoline as well as serum cross-links C-teleopeptide will be assayed in serumurine collected at baseline and 1 3 6 9 and 12 months following liver transplantation
3 Fracture Events Fracture incidence in the RPAH patients has been previously reported as 17 in the first 6 months post-transplantation The fracture rate is now probably lower due to improvements in immunosuppressive therapy It is not anticipated that this study will have sufficient power to detect a significant reduction in fractures however fracture events will be recorded including reduction in height of vertebral bodies at baseline and 12 months post-transplantation
The study groups comprise
Group 1 Zoledronate plus calcium and vit D supplementation
Zoledronate 4 mg will be administered by intravenous infusion details below at baseline within 72 h of liver transplantation followed by zoledronate 4 mg infused as outlined below at 1 3 6 and 9 months post-transplantation PLUS calcium 600mg daily Caltrate one tablet and ergocalciferol 1000 IU daily Ostelin one capsule for 12 months post-transplantation
Group 2 Placebo plus calcium and vit D supplementation
Placebo will consist of 50 ml NSaline infused over 15 minutes as for the zoledronate regime PLUS calcium 600mg daily Caltrate one tablet and ergocalciferol 1000 IU daily Ostelin one capsule Patients with low vitamin D levels 60 nmolL and parathyroid hormone Pth levels above normal 65 should receive ergocalciferol 5000 U daily
ZoledronatePlacebo Infusion regime
Zoledronate 4 mg will be infused in 100 ml NSaline over 15 minutes in patients with a creatinine level 15 times the upper limit of the normal range ie 165 µmolL Patients with renal impairment as indicated by a serum creatinine level 15 x ULN will be discussed on an individual basis with the Medical Adviser of Novartis If zoledronate is to be given an extended infusion time may be used Renal toxicity has been reported with rapid infusions 5 min of 8 mg of zoledronate in patients with pre-existing renal failure Further pharmacokinetic studies in patients with renal failure are being undertaken by Novartis to clarify this area Zoledronate infusion should be freshly prepared and administered without delay
The Hospital Pharmacy will be responsible for providing the infusions zoledronate reconstituted in NSaline or NSaline alone appropriately masked for both Groups 1 and 2
Primary Outcome Measures
1 Bone Density at 3 months post-transplantation
Maximal loss of bone following transplantation is seen by 3 months Earlier data on bone loss in liver transplant patients from the RPAH unit demonstrated an average of 24 bone loss by 3 months post-transplantation Prevention of this effect should provide a precise and early measurement of the effect of zoledronate on transplant-related bone loss Bone density of the hip spine and total body will be measured by dual xray absorptiometry DEXA at baseline not more than 6 months prior to liver transplantation and 3 6 and 12 months following liver transplantation
Secondary Outcome Measures
1 Bone Density at 6 and 12 months post-transplantation
The BMD assessments at 6 and 12 months will assess further changes in bone density between the treated and control groups beyond those assessed at 3 months
2 Biochemical Markers of Bone Metabolism
Biochemical markers of bone formation osteocalcin and total and bone specific alkaline phosphatase and bone resorption urinary collagen cross-links N-teleopeptide and deoxypyridinoline as well as serum cross-links C-teleopeptide will be assayed in serumurine collected at baseline and 1 3 6 9 and 12 months following liver transplantation
3 Fracture Events Fracture incidence in the RPAH patients has been previously reported as 17 in the first 6 months post-transplantation The fracture rate is now probably lower due to improvements in immunosuppressive therapy It is not anticipated that this study will have sufficient power to detect a significant reduction in fractures however fracture events will be recorded including reduction in height of vertebral bodies at baseline and 12 months post-transplantation
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None