Study of Pamidronate for the Prevention of Heterotopic Ossification
|First Received Date ICMJE||December 5, 2005|
|Last Updated Date||September 23, 2008|
|Start Date ICMJE||June 2005|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||Primary endpoint is the radiological Heterotopic Ossification recurrence rate. [ Time Frame: 6 month ]|
|Original Primary Outcome Measures ICMJE
||Primary endpoint is the radiological Heterotopic Ossification recurrence rate.|
|Change History||Complete list of historical versions of study NCT00262392 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Secondary endpoints are the clinical, functional and biochemical outcome (as assessed by several clinical and laboratory markers). [ Time Frame: 6 month ]|
|Original Secondary Outcome Measures ICMJE
||Secondary endpoints are the clinical, functional and biochemical outcome (as assessed by several clinical and laboratory markers).|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Study of Pamidronate for the Prevention of Heterotopic Ossification|
|Official Title ICMJE||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.
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 Type ICMJE||Interventional|
|Study Phase||Not Provided|
|Study Design ICMJE||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
|Condition ICMJE||Heterotopic Ossification|
|Intervention ICMJE||Drug: Pamidronate (AREDIA)
Pamidronate (AREDIA) vs radiation
|Study Arm (s)||
|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.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Withdrawn|
|Estimated Enrollment ICMJE||40|
|Estimated Completion Date||June 2010|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||20 Years and older|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||Not Provided|
|NCT Number ICMJE||NCT00262392|
|Other Study ID Numbers ICMJE||PamidronateforHO271005, HO|
|Has Data Monitoring Committee||No|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||University Hospital, Basel, Switzerland|
|Collaborators ICMJE||FAG (Freie Medizinische Gesellschaft)|
|Information Provided By||University Hospital, Basel, Switzerland|
|Verification Date||September 2008|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP