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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by University Hospital, Basel, Switzerland
Sponsor:
Information provided by (Responsible Party):
Christian Meier, University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier:
NCT00532220
First received: September 19, 2007
Last updated: July 9, 2013
Last verified: July 2013
  Purpose

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 Intervention Phase
Osteonecrosis of the Knee
Bone Marrow Edema of the Knee
Drug: Ibandronate IV
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by University Hospital, Basel, Switzerland:

Primary Outcome Measures:
  • clinical outcome (pain [VAS score]) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • clinical outcome (pain [VAS score]) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • radiological outcome (MRI knee) [ Time Frame: 12 and 24 weeks ] [ Designated as safety issue: No ]
  • number of salvage therapies needed in case persistence is observed during placebo therapy [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: December 2007
Estimated Study Completion Date: July 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00532220

Contacts
Contact: Christian Meier, MD 0041-612649797 christian.meier@unibas.ch

Locations
Switzerland
University Hospital Recruiting
Basel, Switzerland, 4055
Contact: Christian Meier, MD    0041-61-2649797    christian.meier@unibas.ch   
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
  More Information

No publications provided

Responsible Party: Christian Meier, PD, University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT00532220     History of Changes
Other Study ID Numbers: Ro 200-5450
Study First Received: September 19, 2007
Last Updated: July 9, 2013
Health Authority: Switzerland: Swissmedic

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

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

ClinicalTrials.gov processed this record on October 23, 2014