Heterotopic OssificationNCT00262392
Study of Pamidronate for the Prevention of Heterotopic Ossification
A study testing Pamidronate (AREDIA) in people with Heterotopic Ossification, run by University Hospital, Basel, Switzerland.
Trial summary
The purpose of this study is to determine whether Bisphosphonates in comparison to radiation therapy are effective in the prophylaxis and treatment of heterotopic ossification in high risk patients. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Heterotopic Ossification
- What is being tested?
- Pamidronate (AREDIA)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jun 2005to Jun 2010
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Consecutive patients with established HO (Brooker grade III-IV), hospitalized for resection of HO lesions
Who cannot join
- Age <20 years
- Vitamin D deficiency (25OH-Vitamin D <30 ng/ml)
- Renal insufficiency (Clearance <50 ml/min)
- Intolerance of bisphosphonates
- Unable to provide informed consent
About this study
Official title: Study Into the Effect of Pamidronate for the Prevention of Heterotopic Ossification in High-risk Patients: A Randomized Controlled Trial
The purpose of this study is to determine whether Bisphosphonates in comparison to radiation therapy are effective in the prophylaxis and treatment of heterotopic ossification in high risk patients.
Read the detailed description
BACKGROUND: The acquired form of heterotopic ossification (HO) is the most common type of extraskeletal ossification and usually precipitated by a trauma such as total hip arthroplasty [THA] or spinal cord injury. After THA the incidence of HO is as high as 50%, but may reach up to 90% in high risk populations leading to severe functional impairment with ankylotic loss of joint mobility. Nonsteroidal anti-inflammatory drugs (NSAIDs) and external radiation have been used in preventing HO. Specifically, patients with surgical resection of HO at the hip have a high postoperative relapsing rate. Best results were observed after prophylactic radiation treatment with disease recurrence in 33-45% of patients. Data on the effect of bisphosphonates in the prevention of postoperative HO are scarce and mainly limited to the use of the first generation bisphosphonate etidronate. In a retrospective observational study we observed a marked beneficial effect of pamidronate infusions: none of the high risk patients with established HO undergoing surgical removal presented with disease recurrence.
AIM: We therefore aim to prospectively confirm our findings and to evaluate the efficacy of pamidronate for the prevention of recurrent HO after surgical removal of ipsilateral HO. Clinical, biochemical and radiological treatment outcome will be compared to standard clinical practice using preoperative external radiation.
ENDPOINTS: Primary endpoint is the radiological HO recurrence rate. Secondary endpoints are the clinical, functional and biochemical outcome (as assessed by several clinical and laboratory markers).
METHODS: This prospective, randomized trial will be carried out at the University Hospital in Basel/Buderholz in collaboration with the Orthopedic Clinic of the Swiss Paraplegic Centre in Nottwil. Patients who are admitted to the one of the participating orthopedic clinics for removal of HO at the hip will be included in the study. A total number of 40 consecutive patients will be recruited (recruitment phase 24 months) and randomized in a "bisphosphonate group", treated with peri- and postoperative pamidronate infusions (1.0 mg/kg/day for 3 days) and in a "radiation group", treated with external radiation with a single dose of 7 Gy within 24 hours prior to surgical intervention. Additionally, both groups will be treated with NSAIDs for 14 days.
EXPECTED RESULTS: We hypothesize that in treating patients at risk, therapy with pamidronate will be superior in reducing the recurrence rate of established HO as compared to external radiation after surgical resection.
SIGNIFICANCE: Because of the high prevalence in selected risk patients and significant morbidity of HO, this study will offer potential for improving the management of HO. Our study is targeting patients with high risk to develop HO were highly effective prevention is still lacking. Furthermore, a diagnostic marker to identify patients at risk to develop HO would optimize disease management and would allow for early, more successful treatment.
- Conditions
- Heterotopic Ossification
- Being tested
- Pamidronate (AREDIA)
- Keywords
- heterotopic ossification,, prevention,, high risk,, bisphosphonates,, radiotherapy
- Medical subject headings
- Ossification, Heterotopic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pamidronate (AREDIA)Drug
Pamidronate (AREDIA) vs radiation
| Study group | Role | What they receive |
|---|---|---|
| Pamidronate | Experimental | Pamidronate Receives: Drug: Pamidronate (AREDIA) |
| radiation | Active comparator | radiation Receives: Drug: Pamidronate (AREDIA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary endpoint is the radiological Heterotopic Ossification recurrence rate.
Measured: 6 month
Secondary outcomes (1)
Secondary endpoints are the clinical, functional and biochemical outcome (as assessed by several clinical and laboratory markers).
Measured: 6 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2005 (estimated)
- Study startJun 2005
- Primary completionJun 2010
- Study completionJun 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heterotopic OssificationStudies 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Collaborators
- FAG (Freie Medizinische Gesellschaft)
- Investigators
- philipp schuetz, MD, Principal investigator, University Hospital, Basel, SwitzerlandChristian Meier, MD, Study director, University Hospital in Basel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00262392
- Sponsor's protocol ID
- PamidronateforHO271005
- Other IDs
- HO
- Status last verified
- Mar 2015
- First submitted
- 5 Dec 2005
- Last updated
- 10 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Schuetz P, Mueller B, Christ-Crain M, Dick W, Haas H. Amino-bisphosphonates in heterotopic ossification: first experience in five consecutive cases. Spinal Cord. 2005 Oct;43(10):604-10. doi: 10.1038/sj.sc.3101761.
PubMed 15867938
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study Into the Effect of Pamidronate for the Prevention of Heterotopic Ossification in High-risk Patients: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT00262392
- Acronym / sponsor ID
- PamidronateforHO271005
- Conditions
- Heterotopic Ossification
- Keywords
- heterotopic ossification,, prevention,, high risk,, bisphosphonates,, radiotherapy
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Collaborators
- FAG (Freie Medizinische Gesellschaft)
- Study start
- Jun 2005
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 2010 (estimated)
- First posted
- 6 Dec 2005 (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.
The purpose of this study is to determine whether Bisphosphonates in comparison to radiation therapy are effective in the prophylaxis and treatment of heterotopic ossification in high risk patients.
Detailed description
BACKGROUND: The acquired form of heterotopic ossification (HO) is the most common type of extraskeletal ossification and usually precipitated by a trauma such as total hip arthroplasty [THA] or spinal cord injury. After THA the incidence of HO is as high as 50%, but may reach up to 90% in high risk populations leading to severe functional impairment with ankylotic loss of joint mobility. Nonsteroidal anti-inflammatory drugs (NSAIDs) and external radiation have been used in preventing HO. Specifically, patients with surgical resection of HO at the hip have a high postoperative relapsing rate. Best results were observed after prophylactic radiation treatment with disease recurrence in 33-45% of patients. Data on the effect of bisphosphonates in the prevention of postoperative HO are scarce and mainly limited to the use of the first generation bisphosphonate etidronate. In a retrospective observational study we observed a marked beneficial effect of pamidronate infusions: none of the high risk patients with established HO undergoing surgical removal presented with disease recurrence.
AIM: We therefore aim to prospectively confirm our findings and to evaluate the efficacy of pamidronate for the prevention of recurrent HO after surgical removal of ipsilateral HO. Clinical, biochemical and radiological treatment outcome will be compared to standard clinical practice using preoperative external radiation.
ENDPOINTS: Primary endpoint is the radiological HO recurrence rate. Secondary endpoints are the clinical, functional and biochemical outcome (as assessed by several clinical and laboratory markers).
METHODS: This prospective, randomized trial will be carried out at the University Hospital in Basel/Buderholz in collaboration with the Orthopedic Clinic of the Swiss Paraplegic Centre in Nottwil. Patients who are admitted to the one of the participating orthopedic clinics for removal of HO at the hip will be included in the study. A total number of 40 consecutive patients will be recruited (recruitment phase 24 months) and randomized in a "bisphosphonate group", treated with peri- and postoperative pamidronate infusions (1.0 mg/kg/day for 3 days) and in a "radiation group", treated with external radiation with a single dose of 7 Gy within 24 hours prior to surgical intervention. Additionally, both groups will be treated with NSAIDs for 14 days.
EXPECTED RESULTS: We hypothesize that in treating patients at risk, therapy with pamidronate will be superior in reducing the recurrence rate of established HO as compared to external radiation after surgical resection.
SIGNIFICANCE: Because of the high prevalence in selected risk patients and significant morbidity of HO, this study will offer potential for improving the management of HO. Our study is targeting patients with high risk to develop HO were highly effective prevention is still lacking. Furthermore, a diagnostic marker to identify patients at risk to develop HO would optimize disease management and would allow for early, more successful treatment.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pamidronate | Experimental | Drug: Pamidronate (AREDIA)Pamidronate |
| radiation | Active comparator | Drug: Pamidronate (AREDIA)radiation |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Consecutive patients with established HO (Brooker grade III-IV), hospitalized for resection of HO lesions
Key exclusion criteria (5 listed)
- Age <20 years
- Vitamin D deficiency (25OH-Vitamin D <30 ng/ml)
- Renal insufficiency (Clearance <50 ml/min)
- Intolerance of bisphosphonates
- Unable to provide informed consent
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 |
|---|---|---|
| Pamidronate (AREDIA)Pamidronate (AREDIA) vs radiation | Drug | Pamidronate, radiation |
Primary outcome
Primary endpoint is the radiological Heterotopic Ossification recurrence rate.
Time frame: 6 month
1 secondary outcome
Secondary endpoints are the clinical, functional and biochemical outcome (as assessed by several clinical and laboratory markers).
Time frame: 6 month
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2015.
- Background: PubMed 15867938Schuetz P, Mueller B, Christ-Crain M, Dick W, Haas H. Amino-bisphosphonates in heterotopic ossification: first experience in five consecutive cases. Spinal Cord. 2005 Oct;43(10):604-10. doi: 10.1038/sj.sc.3101761.
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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.
philipp schuetz, MD principal investigator
University Hospital, Basel, Switzerland
Christian Meier, MD study director
University Hospital in Basel
Questions about this trial
What is this clinical trial studying?
A study testing Pamidronate (AREDIA) in people with Heterotopic Ossification, run by University Hospital, Basel, 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 5 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: withdrawn, as of the sponsor's last update on 10 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Primary endpoint is the radiological Heterotopic Ossification recurrence rate. (time frame: 6 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00262392, which also lists 1 linked publication.
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 10 Mar 2015.