Study of Pamidronate for the Prevention of Heterotopic Ossification

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborator:
FAG (Freie Medizinische Gesellschaft)
Information provided by:
University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier:
NCT00262392
First received: December 5, 2005
Last updated: September 23, 2008
Last verified: September 2008
  Purpose

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.


Condition Intervention
Heterotopic Ossification
Drug: Pamidronate (AREDIA)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Study Into the Effect of Pamidronate for the Prevention of Heterotopic Ossification in High-Risk Patients: A Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by University Hospital, Basel, Switzerland:

Primary Outcome Measures:
  • Primary endpoint is the radiological Heterotopic Ossification recurrence rate. [ Time Frame: 6 month ]

Secondary Outcome Measures:
  • Secondary endpoints are the clinical, functional and biochemical outcome (as assessed by several clinical and laboratory markers). [ Time Frame: 6 month ]

Estimated Enrollment: 40
Study Start Date: June 2005
Estimated Study Completion Date: June 2010
Arms Assigned Interventions
Experimental: Pamidronate
Pamidronate
Drug: Pamidronate (AREDIA)
Pamidronate (AREDIA) vs radiation
Active Comparator: radiation
radiation
Drug: Pamidronate (AREDIA)
Pamidronate (AREDIA) vs radiation

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.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Consecutive patients with established HO (Brooker grade III-IV), hospitalized for resection of HO lesions

Exclusion criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00262392

Sponsors and Collaborators
University Hospital, Basel, Switzerland
FAG (Freie Medizinische Gesellschaft)
Investigators
Principal Investigator: philipp schuetz, MD University Hospital, Basel, Switzerland
Study Director: Christian Meier, MD University Hospital in Basel
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00262392     History of Changes
Other Study ID Numbers: PamidronateforHO271005, HO
Study First Received: December 5, 2005
Last Updated: September 23, 2008
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University Hospital, Basel, Switzerland:
heterotopic ossification,
prevention,
high risk,
bisphosphonates,
radiotherapy

Additional relevant MeSH terms:
Ossification, Heterotopic
Pathologic Processes
Pamidronate
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014