Bone Marrow Edema of the Knee Clinical Trial
Official title:
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
| Verified date | August 2015 |
| Source | University Hospital, Basel, Switzerland |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | Switzerland: Swissmedic |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 30 |
| Est. completion date | August 2015 |
| Est. primary completion date | August 2015 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 20 Years to 75 Years |
| Eligibility |
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 |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Switzerland | University Hospital | Basel |
| Lead Sponsor | Collaborator |
|---|---|
| University Hospital, Basel, Switzerland |
Switzerland,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | clinical outcome (pain [VAS score]) | 12 weeks | No | |
| Secondary | clinical outcome (pain [VAS score]) | 24 weeks | No | |
| Secondary | radiological outcome (MRI knee) | 12 and 24 weeks | No | |
| Secondary | number of salvage therapies needed in case persistence is observed during placebo therapy | 12 weeks | No |