Ibandronate Versus Placebo in the Prevention of Bone Loss After Renal Transplantation.

Condition(s) targeted: Renal Transplant

Intervention: Placebo (Drug); Ibandronate (Drug)

Phase: Phase 2/Phase 3

Status: Recruiting

Sponsored by: Smerud Medical Research International AS

Official(s) and/or principal investigator(s):
Knut T Smerud, MSc, Study Director, Affiliation: Smerud Medical Research International AS, Drammensveien 41, N-0271 Oslo, Norway

Overall contact:
Anders Hartmann, MD, PhD, Phone: +4723070000, Ext: 1936, Email: anders.hartmann@rikshospitalet.no

Loss of bone mass is a common complication in patients with end-stage-renal failure, both before and particularly after transplantation. In addition to standard underlying therapy with calcium and active vitamin D, we will study the effect of ibandronate (a bisphosphonate) versus placebo on bone mineral density as well as incidence of fracture rates after kidney transplantation. We also wish to study whether any prevented bone loss will also lead to reduced cardiovascular disease. Patients will be followed for 12 months after transplantation, and the ibandronate treatment is one injection every 3 months.

Official title: Ibandronate Versus Placebo as add-on to Active Vitamin D and Calcium in the Prevention of Bone Loss After Renal Transplantation.

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: Difference in percent lumbar BMD change from baseline to 12 months between the two treatment groups.

Secondary outcome:

Lumbar BMD change; absolute and relative

Hip BMD change; absolute and relative

Radial BMD change; absolute and relative

Femural BMD change; absolute and relative

Change in height

Change in biochemical efficacy and bone markers

Change in HRQoL scores (SF-36 and mini OQOL)

Incidence of post-transplant complications

Frequency of clinically significant safety laboratory variables

Adverse event rates

Detailed description: Demographic, medical history, previous and current medication, as well as baseline measurements of Bone Mineral Density (BMD), laboratory efficacy and safety variables as well as Quality-of-Life scores will be undertaken in the period from 1 week prior to transplantation until 1 week after transplantation. In this period, any existing fractures will be determined using traditional x-ray of the thoraco-lumbar columna. Renal graft functioning as well as transplantation complications will be followed tightly, and calcium supplementation as well as active vitamin D (calcitriol) will be administered together with the standard immunosuppressive regimen.

As soon as patients have recovered from transplantation, and renal functioning is considered sufficiently stable, and no later than 28 days after the transplantation, qualified patients will be randomised to receive either ibandronate or placebo, stratified by gender. Bone mineral density and most of the clinical data and laboratory tests will then be followed until 12 months after transplantation as described in the attached flowchart (section 11. 1), with hospital visits for administration of study drugs and follow-up of at 13, 26, 39 and 52 weeks after transplantation. Furthermore, all the patients will be followed prospectively from the time of transplantation and for ten years with regard to cardiovascular events. Data concerning cardiovascular events will be collected from the Norwegian renal registry for the whole study population in the follow up period of about 10 years.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Renal transplant recipients

- Adults, ≥ 18 years of age

- Either gender

- Signed informed consent

Exclusion Criteria:

- Persisting s-Ca > 2. 55 mmol/L (through the first two weeks after transplantation)

- Impaired graft functioning (estimated GFR <30 ml/min)

- Previous (within the last 12 months) treatment with bisphosphonates, sodium fluoride,

calcitonin, strontium, PTH, SERM, growth hormone or anabolic steroids at any time before transplantation.

- Known adynamic bone disease

- Previous parathyroidectomy

- Pregnant or lactating females or females of childbearing potential who do not use an

approved method of contraception (oral contraceptives or IUD); positive urine pregnancy test, where applicable.

- Use of any investigational drug (s) and/or device(s)

- Previous participation in this trial

- History of hypersensitivity to bisphosphonates

Anders Hartmann, MD, PhD, Phone: +4723070000, Ext: 1936, Email: anders.hartmann@rikshospitalet.no

Rikshospitalet-Radiumhospitalet Medical Center, Oslo 0027, Norway; Recruiting

Starting date: January 2007
Ending date: December 2010
Last updated: August 6, 2009