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

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

Tracking Information

• First Submitted Date: September 19, 2007
• First Posted Date: September 20, 2007
• Last Update Posted Date: August 26, 2015
• Study Start Date: December 2007
• Actual Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 19, 2007): clinical outcome (pain [VAS score]) [ Time Frame: 12 weeks ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 19, 2007)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief 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
• 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Osteonecrosis of the Knee
• Bone Marrow Edema of the Knee

Intervention

• 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)
• Drug: Placebo
  Placebo IV, divided in 4 single infusions within 2 weeks, followed by a fifth infusion after 3 months (V4)

Study Arms

• Active Comparator: A
  Intervention: Drug: Ibandronate IV
• Placebo Comparator: B
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 19, 2007): 30
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: August 2015
• Actual Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Switzerland

Administrative Information

• NCT Number: NCT00532220
• Other Study ID Numbers: Ro 200-5450
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Christian Meier, University Hospital, Basel, Switzerland
• Study Sponsor: University Hospital, Basel, Switzerland
• Collaborators: Not Provided

Investigators

• Principal Investigator: Christian Meier, MD; University Hospital, Basel, Switzerland
• Principal Investigator: Marius E Kraenzlin, MD; University Hospital, Basel, Switzerland

• PRS Account: University Hospital, Basel, Switzerland
• Verification Date: August 2015