Osteonecrosis of the KneePhase 3NCT00532220
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
A Phase 3 study testing Ibandronate IV in people with Osteonecrosis of the Knee and Bone Marrow Edema of the Knee, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- Osteonecrosis of the Knee, Bone Marrow Edema of the Knee
- What is being tested?
- Ibandronate IV
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteSwitzerland
- Study dates
- Dec 2007to Aug 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 20 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Consecutive patients with newly diagnosed BME in relation to ON, confirmed by MRI scan
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read more
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.
- Being tested
- Ibandronate IV, Placebo
- Keywords
- osteonecrosis, bone marrow edema, ibandronate, bisphosphonate, knee
- Medical subject headings
- Osteonecrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ibandronate IVDrug
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)
PlaceboDrug
Placebo IV, divided in 4 single infusions within 2 weeks, followed by a fifth infusion after 3 months (V4)
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | Not described Receives: Drug: Ibandronate IV |
| B | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
clinical outcome (pain [VAS score])
Measured: 12 weeks
Secondary outcomes (3)
clinical outcome (pain [VAS score])
Measured: 24 weeks
radiological outcome (MRI knee)
Measured: 12 and 24 weeks
number of salvage therapies needed in case persistence is observed during placebo therapy
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2007 (estimated)
- Study startDec 2007
- Primary completionAug 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Osteonecrosis of the KneeStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Christian Meier, University Hospital, Basel, Switzerland
- Investigators
- Christian Meier, MD, Principal investigator, University Hospital, Basel, SwitzerlandMarius E Kraenzlin, MD, Principal investigator, University Hospital, Basel, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00532220
- Sponsor's protocol ID
- Ro 200-5450
- Status last verified
- Aug 2015
- First submitted
- 19 Sep 2007
- Last updated
- 26 Aug 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00532220
- Acronym / sponsor ID
- Ro 200-5450
- Keywords
- osteonecrosis, bone marrow edema, ibandronate, bisphosphonate, knee
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- Dec 2007
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 20 Sep 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Drug: Ibandronate IV |
| B | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Consecutive patients with newly diagnosed BME in relation to ON, confirmed by MRI scan
Key exclusion criteria (9 listed)
- 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
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 |
|---|---|---|
| Ibandronate IVIbandronate 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 | A |
| PlaceboPlacebo IV, divided in 4 single infusions within 2 weeks, followed by a fifth infusion after 3 months (V4) | Drug | B |
Primary outcome
clinical outcome (pain [VAS score])
Time frame: 12 weeks
3 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2015.
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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.
Christian Meier, MD principal investigator
University Hospital, Basel, Switzerland
Marius E Kraenzlin, MD principal investigator
University Hospital, Basel, Switzerland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ibandronate IV in people with Osteonecrosis of the Knee and Bone Marrow Edema of the Knee, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
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 1 inclusion and 9 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 26 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
clinical outcome (pain [VAS score]) (time frame: 12 weeks). 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 26 Aug 2015.