Efficacy of Zoledronic Acid in Preventing Collapse of the Osteonecrotic Femoral Head (EZAPCOFH)

This study has been completed.
Sponsor:
Collaborator:
Novartis Korea Ltd.
Information provided by (Responsible Party):
Kyung-Hoi Koo, Seoul National University Bundang Hospital
ClinicalTrials.gov Identifier:
NCT00939900
First received: July 14, 2009
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to test the effect of zoledronic acid over 2 years in preventing early collapse and progression of joint dome depression (≥ 2 mm by X-ray) of the femoral head in patients with large (> 30%: criteria according to Kim et al) nontraumatic osteonecrosis.


Condition Intervention Phase
Avascular Necrosis of Femoral Head
Drug: zoledronic acid (aclasta)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multicenter, Open-labeled, Randomized Clinical Trial to Determine the Efficacy of Zoledronic Acid in Preventing Collapse of the Osteonecrotic Femoral Head

Resource links provided by NLM:


Further study details as provided by Seoul National University Bundang Hospital:

Primary Outcome Measures:
  • We will evaluate percent of collapse of femoral head measured by X-ray and CT and/or MRI (pelvis AP, frog leg lateral, hip axial), and degree of dome depression over 24 months [ Time Frame: Measurement will be done at 0m, 3m, 6m, 9m, 12m, 18m, 24m) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Collpase rate of femoral head [ Time Frame: Measurement will be done at 0m, 3m, 6m, 9m, 12m, 18m, 24m) ] [ Designated as safety issue: Yes ]
  • Change of HHS (Harris Hip Scores), WOMAC score, SF-36 [ Time Frame: Measurement will be done at 0m, 3m, 6m, 9m, 12m, 18m, 24m) ] [ Designated as safety issue: Yes ]
  • Time to collapse of femoral head [ Time Frame: Measurement will be done at 0m, 3m, 6m, 9m, 12m, 18m, 24m) ] [ Designated as safety issue: Yes ]
  • Time to total arthroplasty or joint preserving surgery [ Time Frame: Measurement will be done at 0m, 3m, 6m, 9m, 12m, 18m, 24m) ] [ Designated as safety issue: Yes ]

Enrollment: 110
Study Start Date: July 2009
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: aclasta
aclasta group
Drug: zoledronic acid (aclasta)
Once-yearly administration of 5mg zoledronic acid intravenously (dosage of treatment of osteoporosis) (+ calcium:1,200mg/day, VitD:800IU/day) during study period
Other Name: aclasta
No Intervention: control
control group

Detailed Description:

Until now, the best treatment option in early (precollapse) large osteonecrosis femoral head is vascularizing fibular graft. However, it requires high microsurgical technique. Also it needs very long operation time (3-6hours), and morbidity associated with surgery is not low. In early stage osteonecrosis, osteoclasts are activated and resorb the necrotic portion of bone and osteoblasts are followed to lay down new bone. This process can weaken the bone function to support loading and can lead to collapse of bone. Bisphophonate can inhibit this osteoclastic bone resorption and enhance osteoblastic new bone formation. Recently, everyday oral intake of alendronate with vitamin D and calcium had a high success rate to prevent the collapse and decrease of hip joint pain in a short-term follow-up. However, the compliance or adherence to everyday oral intake is questionable. Moreover, the exact comparison based on MRI according to various classifications is not available currently. There is no report about the effect of zoledronic acid to prevent early collapse and progression of joint dome depression (≥2 mm by X-ray) of the early stage large nontraumatic osteonecrosis of the femoral head or its effect on MRI signal change after infusion of zoledronic acid in noncollapsed cases (estimated about 30% of cases) The investigators need a controlled randomized multicenter interventional study about the efficacy of bisphophonates in the treatment of ONFH.

  Eligibility

Ages Eligible for Study:   19 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient who agree to clinical trial
  • Patient who are more than 18 years of age
  • Osteonecrosis of the femoral head
  • Steinberg stage I, II non traumatic osteonecrosis of femoral head
  • Necrotic area of > 30% (HJ Kim et al )
  • JIC (Japanese Investigation Committee): C1 or C2 lateral lesion (by X-ray or MRI)

Exclusion Criteria:

  • Patients who are pregnant (patients who are of child bearing potential who are not practicing a reliable contraceptive method (oral, subcutaneous, mechanical, or surgical contraception)
  • Patients who have contraindicated condition to zoledronic acid such as chronic renal failure (calculated creatinine clearance less than 35.0 ml/min), severe heart disease such as atrial fibrillation, sensitive to bisphosphonates and hypocalcemia (serum calcium less than 8 mg/dl or 2.0 mmol/L)
  • Patients who have collapsed lesion including subchonral fracture
  • Patients who have multiple lesion of osteonecrosis of femoral head
  • Patients who received other kinds of bisphophonates or anabolic agents before zoledronic acid use
  • Patients with any medical or psychiatric condition which, in the Investigator's opinion would preclude the participant from adhering to the Protocol or completing the trial per protocol
  • Patients who are considered potentially unreliable and patients who may not reliably attend study visits
  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: NCT00939900

Locations
Korea, Republic of
Seoul national University Bundang Hospital
Seongnam-Si, Gyeonggi-do, Korea, Republic of, 463-707
Sponsors and Collaborators
Seoul National University Bundang Hospital
Novartis Korea Ltd.
Investigators
Principal Investigator: Kyung-Hoi Koo, professor Seoul National University Bundang Hospital
  More Information

No publications provided

Responsible Party: Kyung-Hoi Koo, Professor, Seoul National University Bundang Hospital
ClinicalTrials.gov Identifier: NCT00939900     History of Changes
Other Study ID Numbers: CZOL446HKR08T
Study First Received: July 14, 2009
Last Updated: May 12, 2014
Health Authority: United States: Food and Drug Administration
Korea: Food and Drug Administration

Keywords provided by Seoul National University Bundang Hospital:
avascular necrosis of femoral head
bisphosphonate
collapse

Additional relevant MeSH terms:
Necrosis
Osteonecrosis
Shock
Femur Head Necrosis
Pathologic Processes
Bone Diseases
Musculoskeletal Diseases
Zoledronic acid
Diphosphonates
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 28, 2014