Bone Marrow EdemaPhase 3ZoMARSNCT01348269
Assessment of Efficacy of Zoledronic Acid in the Treatment of Bone Marrow Edema Syndrome
A Phase 3 study testing Aclasta in people with Bone Marrow Edema, run by Wuerzburg University Hospital at 2 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bone Marrow Edema
- What is being tested?
- Aclasta
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 2 sitesGermany
- Study dates
- May 2011to 26 Aug 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- - 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
Show all 28Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
Orthopedic Center for Musculoskeletal Research, Orthopedic Department, University of Wuerzburg
Würzburg, Bavaria, 97074
Department of trauma, hand, reconstructive and plastic, University of Wuerzburg
Würzburg, Bavaria, 97080
About this study
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
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.
- Conditions
- Bone Marrow Edema
- Being tested
- Aclasta, Placebo
- Keywords
- bone marrow edema, Aclasta
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AclastaDrug
1 x intravenous non-current drip (infusion)
PlaceboDrug
NaCl Solution
| Study group | Role | What they receive |
|---|---|---|
| Aclasta | Active comparator | Not described Receives: Drug: Aclasta |
| NaCl Solution | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction of the Edema Area
The volume of the edema in cm³ is defined as biometric data measured by the use of MRI before and six weeks after treatment. Edema volume at screening was set to 100%. Edema volume six weeks after study drug administration was provdied as percentage reduction compared to the value at screening
Measured: Week 6 after administration of a single intravenous dose of zoledronic acid (5 mg)
Secondary outcomes (12)
Reduction of Pain (VAS)
Reduction of pain as measured by a Visual Analog Scale (VAS). Range 0-100 with higher values indicating worse pain.
Measured: Assessment at week 3
Reduction of Pain
Reduction of pain as measured by a visual analog scale (VAS). Range 0-100. Higher values indicating worse pain.
Measured: Assessment at week 6
Quality of Life (Qualeffo-41 Questionnaire)
Quality of life as measured by the Qualeffo-41 questionnaire - a quality of life questionnaire in patients with fractures of the European Foundation for Osteoporosis Higher values indicate worse quality of life
Measured: Assessment at week 3
Quality of Life (Qualeffo-41 Questionnaire)
Quality of life as measured by the Qualeffo-41 questionnaire - a quality of life questionnaire in patients with vertebral fractures of the European Foundation for Osteoporosis
Measured: Assessment at week 6
Subjective Estimation of Medical Condition (PDI)
Subjective estimation of medical condition as assessed by PDI (Pain Disability Index). Range 0-70. The higher the index the greater the person's disability due to pain.
Measured: Assessment at week 3
Subjective Estimation of Medical Condition (PDI)
Subjective estimation of medical condition as assessed by PDI (Pain Disability Index)
Measured: Assessment at week 6
Number of Additional Medicinal Visits
Number of additional medicinal visits until week 3
Measured: Assessment at week 3
Number of Additional Medicinal Visits
Aggregated number of unscheduled medicinal visits
Measured: Assessment at week 6
Number of Days of Illness
Aggregated number of days of illness i.e. sick leave from work, assessed until week 6
Measured: Assessment at week 6
Number of Days of Illness
Number of days of illness assessed until week 6
Measured: Assessment at week 6
Number of Aseptic Bone Necrosis and Fatigue Fractures
Assessment of number of patients withaseptic bone necrosis and/or fatigue fractures.
Measured: Baseline until end of study (week 12)
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
Measured: Week 3, 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2011 (estimated)
- Study startMay 2011
- Primary completion26 Aug 2015
- Study completion26 Aug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Bone Marrow EdemaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wuerzburg University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Crolll Gmbh, University of Wuerzburg
- Responsible party
- Principal investigator, Dr. Lothar Seefried, Orthopaedische Klinik Koenig-Ludwig-Haus
- Investigators
- Rainer Meffert, Prof. Dr., Study chair, Department of trauma, hand, reconstructive and plastic, University of Wuerzburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01348269
- Sponsor's protocol ID
- CZOL446HDE38T
- Acronym
- ZoMARS
- Status last verified
- Aug 2024
- First submitted
- 2 May 2011
- Last updated
- 13 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01348269
- Acronym / sponsor ID
- ZoMARS / CZOL446HDE38T
- Conditions
- Bone Marrow Edema
- Keywords
- bone marrow edema, Aclasta
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Wuerzburg University HospitalUniversity, hospital or other
- Collaborators
- Crolll Gmbh, University of Wuerzburg
- Study start
- May 2011 (actual)
- Primary completion
- 26 Aug 2015 (actual)
- Study completion
- 26 Aug 2015 (actual)
- First posted
- 5 May 2011 (estimated)
- Results
- Posted 13 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aclasta | Active comparator | Drug: Aclasta |
| NaCl Solution | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (28 listed)
- - 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aclasta1 x intravenous non-current drip (infusion) | Drug | Aclasta |
| PlaceboNaCl Solution | Drug | NaCl Solution |
Primary outcome
Reduction of the Edema Area
Time frame: Week 6 after administration of a single intravenous dose of zoledronic acid (5 mg)
The volume of the edema in cm³ is defined as biometric data measured by the use of MRI before and six weeks after treatment. Edema volume at screening was set to 100%. Edema volume six weeks after study drug administration was provdied as percentage reduction compared to the value at screening
12 secondary outcomes
Reduction of Pain (VAS)
Time frame: Assessment at week 3
Reduction of Pain
Time frame: Assessment at week 6
Quality of Life (Qualeffo-41 Questionnaire)
Time frame: Assessment at week 3
Quality of Life (Qualeffo-41 Questionnaire)
Time frame: Assessment at week 6
Subjective Estimation of Medical Condition (PDI)
Time frame: Assessment at week 3
Subjective Estimation of Medical Condition (PDI)
Time frame: Assessment at week 6
Number of Additional Medicinal Visits
Time frame: Assessment at week 3
Number of Additional Medicinal Visits
Time frame: Assessment at week 6
Number of Days of Illness
Time frame: Assessment at week 6
Number of Days of Illness
Time frame: Assessment at week 6
Number of Aseptic Bone Necrosis and Fatigue Fractures
Time frame: Baseline until end of study (week 12)
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Time frame: Week 3, 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Recruiting
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rainer Meffert, Prof. Dr. study chair
Department of trauma, hand, reconstructive and plastic, University of Wuerzburg
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Aclasta in people with Bone Marrow Edema, run by Wuerzburg University Hospital at 2 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction of the Edema Area (time frame: Week 6 after administration of a single intravenous dose of zoledronic acid (5 mg)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2024.