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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

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ClinicalTrials.gov Identifier: NCT00532220
Recruitment Status : Completed
First Posted : September 20, 2007
Last Update Posted : August 26, 2015
Sponsor:
Information provided by (Responsible Party):
Christian Meier, University Hospital, Basel, Switzerland

Brief 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.


Condition or disease Intervention/treatment Phase
Osteonecrosis of the Knee Bone Marrow Edema of the Knee Drug: Ibandronate IV Drug: Placebo Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Study Start Date : December 2007
Actual Primary Completion Date : August 2015
Actual Study Completion Date : August 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Edema Osteonecrosis
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: A Drug: Ibandronate IV
Ibandronate IV (Bonviva® IV), 10.5 mg divided in 4 single infusions within 2 weeks(1x1.5 mg, 3x3 mg), followed by a fifth infusion after 3 months (V4)
Placebo Comparator: B Drug: Placebo
Placebo IV, divided in 4 single infusions within 2 weeks, followed by a fifth infusion after 3 months (V4)



Primary Outcome Measures :
  1. clinical outcome (pain [VAS score]) [ Time Frame: 12 weeks ]

Secondary Outcome Measures :
  1. clinical outcome (pain [VAS score]) [ Time Frame: 24 weeks ]
  2. radiological outcome (MRI knee) [ Time Frame: 12 and 24 weeks ]
  3. number of salvage therapies needed in case persistence is observed during placebo therapy [ Time Frame: 12 weeks ]


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Ages Eligible for Study:   20 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00532220


Locations
Switzerland
University Hospital
Basel, Switzerland, 4031
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Investigators
Principal Investigator: Christian Meier, MD University Hospital, Basel, Switzerland
Principal Investigator: Marius E Kraenzlin, MD University Hospital, Basel, Switzerland

Responsible Party: Christian Meier, PD, University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT00532220     History of Changes
Other Study ID Numbers: Ro 200-5450
First Posted: September 20, 2007    Key Record Dates
Last Update Posted: August 26, 2015
Last Verified: August 2015

Keywords provided by Christian Meier, University Hospital, Basel, Switzerland:
osteonecrosis
bone marrow edema
ibandronate
bisphosphonate
knee

Additional relevant MeSH terms:
Edema
Osteonecrosis
Signs and Symptoms
Bone Diseases
Musculoskeletal Diseases
Necrosis
Pathologic Processes
Ibandronic acid
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs