Clinical trial NCT01348269: Assessment of Efficacy of Zoledronic Acid in the Treatment of Bone Marrow Edema Syndrome
Official title: A Prospective, Bi-centric,Randomized, Primary Double-blind, Placebo-controlled Phase III Study to Assess the Efficacy of Zoledronic Acid in the Treatment of Bone Marrow Edema Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bone Marrow Edema
Keywords: bone marrow edema
Aclasta
Lead sponsor: Wuerzburg University Hospital
Sponsor class: OTHER
Collaborators: name: Crolll Gmbh
name: University of Wuerzburg
First posted: 2011-05-05
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary aim is to test the reduction of bone marrow edema syndrome after a singular intravenous treatment with Zoledronic Acid within 6 weeks compared to placebo. The volume of the edema is defined as biometric data measured by the use of MRT before and six weeks after treatment. The hypothesis has to be checked whether Zoledronic Acid is efficient in the treatment of painful bone marrow edema. A statistically significant reduction of the edema in the MRT is considered as evidence for efficacy.


Eligibility criteria: Inclusion Criteria:

* Men: age over ≥ 18 years or women: age over ≥ 18 years with finished reproductivity according to the following definition:
* ≥ 12 month persistent natural (spontaneous) amenorrhoea (women aged \<50: additionally: FSH \>40MIE/ml and estrogen deficiency of \<30pg/ml or a negative estrogen test)
* status post hysterectomy and / or bilateral oophorectomy
* finished reproduction planning
* secure diagnosis of bone marrow edema using MRT
* current osteologic basic laboratory values (≤ 4 weeks before V2) according to DVO criteria
* presence of an personally signed informed consent for the participation in the study

Exclusion Criteria:

* - subchondral bone loss or already occurred cartilage damage due to the bone marrow edema
* reactive bone marrow edema with advanced arthrotic changes in the adjacent joint (grade III and IV according to Kellgren and Lawrence)
* patients with edematous changes in bone marrow due to the diagnosis of M. Sudeck / algodystrophy / Complex Regional Pain Syndrome (CRPS)
* patients with known hypo- and hyperparathyroidism, osteogenesis imperfecta, osteomalacia, M. Paget or another systemic skeletal diseases, except osteoporosis
* patients with bone necrosis in the painful skeletal region
* patients with infectious process at the affected bone or the adjacent joint and adjacent soft parts, respectively
* patients with diagnosed or assumed rheumatoid arthritis, Lupus erythematodes, collagenosis or vasculitides
* patients with advanced renal insufficiency (GFR according to Cockcroft

  / Gault ≤ 40 ml/min/KO)
* patients with malignant diseases with osseous manifestation in anamnesis/history
* status post malignant basic/primary disease with large dosed chemotherapy
* current or massive dose therapy completed before less than 6 weeks (\>7.5mg prednisolon equivalent) with glucocorticoids
* patients with a malignant tumor disease within the past 5 years, independent from the affected organ system and independent from the implemented treatment, the presence of a relapse or metastatic invasion, except basal cell carcinoma and squamous-cell carcinoma of the skin Current treatment due to uveitis
* vague/ambiguous hyper- or hypocalcemia, hyper- or hypophosphatemia
* etiological vague/ambiguous AP-increase
* symptomatic renal calculus or nephrocalcinosis within 2 years before V2
* recent fracture within the last 3 months independent of the localisation
* non consolidated fractures
* previous treatment with i.v. bisphosphonates within the last 12 months
* previous treatment with oral bisphosphonates within the last 12 months and longer than 3 months
* pre-treatment with prostacyclin analogs (Ilomedin® / Iloprost®) within the past 6 months
* Current treatment due to inflammatory diseases of the jaw area as well as planned tooth extractions or tooth extractions less than 6 months ago or oral surgery implant treatment
* pregnancy or nursing period
* patients immediately involved in the conduction of the trial and relatives
* patients with current proceedings related to the bone marrow edema
* patients for which the participation in the study carries an increased risk under consideration of the health condition due to the assessment of the investigator
* participation in another clinical trial within 30 days before study start or during the trial
* participation of patient who might be dependent on the investigator, also the spouse, parents or children

Primary outcomes:
measure: Reduction of the Edema Area
timeFrame: Week 6 after administration of a single intravenous dose of zoledronic acid (5 mg)
Secondary outcomes:
measure: Reduction of Pain (VAS)
timeFrame: Assessment at week 3
measure: Reduction of Pain
timeFrame: Assessment at week 6
measure: Quality of Life (Qualeffo-41 Questionnaire)
timeFrame: Assessment at week 3
measure: Quality of Life (Qualeffo-41 Questionnaire)
timeFrame: Assessment at week 6
measure: Subjective Estimation of Medical Condition (PDI)
timeFrame: Assessment at week 3
measure: Subjective Estimation of Medical Condition (PDI)
timeFrame: Assessment at week 6
measure: Number of Additional Medicinal Visits
timeFrame: Assessment at week 3
measure: Number of Additional Medicinal Visits
timeFrame: Assessment at week 6
measure: Number of Days of Illness
timeFrame: Assessment at week 6
measure: Number of Days of Illness
timeFrame: Assessment at week 6
measure: Number of Aseptic Bone Necrosis and Fatigue Fractures
timeFrame: Baseline until end of study (week 12)
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
timeFrame: Week 3, 6
Other outcomes:
Locations:
city: Wuerzburg
country: Germany
facility: Orthopedic Center for Musculoskeletal Research, Orthopedic Department, University of Wuerzburg
state: Bavaria
city: Wuerzburg
country: Germany
facility: Department of trauma, hand, reconstructive and plastic, University of Wuerzburg
state: Bavaria
Study officials:
affiliation: Department of trauma, hand, reconstructive and plastic, University of Wuerzburg
name: Rainer Meffert, Prof. Dr.
role: STUDY_CHAIR
References: