The Effect of Zoledronic Acid on Bone Density in Liver Transplant Patients
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|ClinicalTrials.gov Identifier: NCT00114556|
Recruitment Status : Completed
First Posted : June 16, 2005
Last Update Posted : May 9, 2006
|First Submitted Date ICMJE||June 15, 2005|
|First Posted Date ICMJE||June 16, 2005|
|Last Update Posted Date||May 9, 2006|
|Study Start Date ICMJE||February 2000|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE||Same as current|
|Current Secondary Outcome Measures ICMJE
||bone turnover markers|
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||The Effect of Zoledronic Acid on Bone Density in Liver Transplant Patients|
|Official Title ICMJE||The Effect Of The Bisphosphonate, Zoledronic Acid, On Bone Density In Liver Transplant Patients - A Prospective, Randomised, Controlled Clinical Trial|
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.
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 N/Saline 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 nmol/L) and parathyroid hormone (Pth) levels above normal >6.5 should receive ergocalciferol 5000 U daily.
Zoledronate/Placebo Infusion regime
Zoledronate 4 mg will be infused in 100 ml N/Saline over 15 minutes in patients with a creatinine level <1.5 times the upper limit of the normal range (i.e <165 µmol/L). Patients with renal impairment as indicated by a serum creatinine level >1.5 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 N/Saline or N/Saline 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:
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 4|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Single Group Assignment
Primary Purpose: Prevention
|Intervention ICMJE||Drug: zoledronic acid|
|Study Arms ICMJE||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Original Enrollment ICMJE||Same as current|
|Study Completion Date ICMJE||August 2004|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages ICMJE||17 Years to 70 Years (Child, Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Australia|
|Removed Location Countries|
|NCT Number ICMJE||NCT00114556|
|Other Study ID Numbers ICMJE||CZOL446 AU02|
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||Royal Prince Alfred Hospital, Sydney, Australia|
|PRS Account||Royal Prince Alfred Hospital, Sydney, Australia|
|Verification Date||December 2004|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP