Assessment of Efficacy of Zoledronic Acid in the Treatment of Bone Marrow Edema Syndrome (ZoMARS)

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

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.

Study Overview

• Status: Completed
• Conditions: Bone Marrow Edema
• Intervention / Treatment: Drug: Aclasta; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Bavaria
    • Wuerzburg, Bavaria, Germany, 97074
      • Orthopedic Center for Musculoskeletal Research, Orthopedic Department, University of Wuerzburg
    • Wuerzburg, Bavaria, Germany, 97080
      • Department of trauma, hand, reconstructive and plastic, University of Wuerzburg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: NaCl Solution	Drug: Placebo; NaCl Solution
Active Comparator: Aclasta	Drug: Aclasta; 1 x intravenous non-current drip (infusion)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Reduction of the Edema area	Week 6 after study start

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of pain (VAS)		Week 0, 3, 6
Quality of life (Qualeffo-41 questionnaire - Quality of life questionnaire of the European Foundation for Osteoporosis)		Week 0, 3, 6
Subjective estimation of medical condition (PDI)		Week 0, 3, 6
Number of additional medicinal visits		Week 3, 6
Number of days of illness		Week 3, 6
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	including changes in the following parameters according to DVO guidelines: Calcium, Phosphate, Creatinin-Clearance (Cockcroft-Gault), Alkaline Phosphatase, γGT, CRP	Week 3, 6

Collaborators and Investigators

• Sponsor: Wuerzburg University Hospital
• Collaborators: University of Wuerzburg; Crolll Gmbh
• Investigators: Study Chair: Rainer Meffert, Prof. Dr., Department of trauma, hand, reconstructive and plastic, University of Wuerzburg

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2011
• Primary Completion (Actual): August 26, 2015
• Study Completion (Actual): August 26, 2015

Study Registration Dates

• First Submitted: May 2, 2011
• First Submitted That Met QC Criteria: May 4, 2011
• First Posted (Estimate): May 5, 2011

Study Record Updates

• Last Update Posted (Actual): June 8, 2017
• Last Update Submitted That Met QC Criteria: June 7, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: bone marrow edema; Aclasta
• Additional Relevant MeSH Terms: Edema; Physiological Effects of Drugs; Bone Density Conservation Agents; Zoledronic Acid
• Other Study ID Numbers: CZOL446HDE38T