Study Into the Effect of Ibandronate for the Treatment of Bone Marrow Edema in Relation to Spontaneous or Non-Traumatic Osteonecrosis of the Knee: A Randomized Double-Blind, Placebo-Controlled Trial
Information source: University Hospital, Basel, Switzerland
Information obtained from ClinicalTrials.gov on October 19, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Osteonecrosis of the Knee; Bone Marrow Edema of the Knee
Intervention: Ibandronate IV (Drug); Placebo (Drug)
Phase: Phase 3
Status: Recruiting
Sponsored by: University Hospital, Basel, Switzerland Official(s) and/or principal investigator(s):
Christian Meier, MD, Principal Investigator, Affiliation: University Hospital Basel
Marius E Kraenzlin, MD, Principal Investigator, Affiliation: University Hospital Basel
Overall contact:
Christian Meier, MD, Phone: 0041-612649797, Email: christian.meier@unibas.ch
Summary
BACKGROUND: Bone marrow edema (BME) in the knee occurs as a localized inflammatory disease
in relation to spontaneous or non-traumatic osteonecrosis (ON). Prognosis of BME/ON in the
course after knee arthroscopy appears to be poor and in most cases results in knee
arthroplasty. Treatment options of ON depend in general on the size of the lesion. Smaller
lesions are managed by mechanical unloading and use of non-steroidal anti-inflammatory
drugs, larger lesion in general requires osteotomy or arthroplasty. In animal studies it has
been shown that bisphosphonates prevent resorption of necrotic bone during ischemic necrosis
and revascularization. In humans, bisphosphonate treatment has been used successfully in
bone marrow oedema and avascular necrosis of the femoral head.
In an observational study using bisphosphonates (ibandronate, pamidronate) in patients with
either spontaneous or (believed to be) arthroscopy-induced BME of the knee a significant
rapid and sustained pain relief was observed with a mean decrease on the pain scale on the
visual analogue scale of over 60% after 3 months and of 80% after 6 months. Our experience
suggests an apparent beneficial effect of amino-bisphosphonates in the treatment of BME of
the knee.
AIM: This randomized, double-blind, placebo-controlled study aims to provide data on
clinical, biochemical and radiological outcome of patients with bone marrow edema in
relation to spontaneous or arthroscopy-induced ON of the knee treated with ibandronate or
placebo.
ENDPOINTS: The primary objective is to demonstrate the superiority of treatment with
ibandronate compared to placebo regarding clinical outcome (pain [VAS score]) in spontaneous
or arthroscopy-induced BME/ON of the knee after 12 weeks. Secondary objectives include a)
clinical outcome (pain [VAS score]) after 24 weeks, b) the evaluation of the radiological
outcome (MRI scan) at 12 and 48 weeks, c) the changes in biochemical markers of bone
turnover, and d) the number of salvage therapies needed in case persistence is observed
during placebo therapy.
METHODS: The study is designed as a single-center, randomized double-blind,
placebo-controlled trial. A total number of 30 patients with BME/ON will be recruited. Each
patient will be randomized in a 1: 1 ratio to receive ibandronate IV or placebo IV.
Additionally, all patients will receive 500 mg calcium and 400 IU vitamin D per day
throughout the study, and diclofenac/esomeprazole for initial 3 months (blinded treatment
duration 24 weeks). Baseline and follow-up data collection will contain all variables needed
for evaluation of clinical, biochemical and radiological evaluation of treatment efficacy.
EXPECTED RESULTS: We hypothesize that treating patients with BME/ON of the knee, therapy
with ibandronate will be superior in reducing pain, and radiological findings as compared to
placebo.
Clinical Details
Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Primary outcome: clinical outcome (pain [VAS score])
Secondary outcome: clinical outcome (pain [VAS score])radiological outcome (MRI knee) number of salvage therapies needed in case persistence is observed during placebo therapy
Eligibility
Minimum age: 20 Years.
Maximum age: 75 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Consecutive patients with newly diagnosed BME in relation to ON, confirmed by MRI
scan
Exclusion Criteria:
- Baseline renal insufficiency (calculated creatinine clearance <50 ml/min)
- Baseline hypocalcemia (serum calcium <2. 0 mmol/l)
- Premenopausal women without adequate contraception
- Hypersensitivity to bisphosphonates
- Prior treatment with bisphosphonates within the last 2 years prior to randomization
- Prior treatment with calcitonin within the last month prior to randomization
- Treatment with any investigational drug within 30 days prior to randomization
- Any medical or psychiatric condition which, in the opinion of the investigator, would
preclude the participant from adhering to the protocol or completing the trial per
protocol
- Unable to provide informed consent
Locations and Contacts
Christian Meier, MD, Phone: 0041-612649797, Email: christian.meier@unibas.ch
University Hospital, Basel 4055, Switzerland; Recruiting
Christian Meier, MD, Phone: 0041-61-2649797, Email: christian.meier@unibas.ch
Additional Information
Starting date: December 2007
Ending date: May 2009
Last updated: September 23, 2008
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