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

Multicenter, Open-labeled, Randomized Clinical Trial to Determine the Efficacy of Zoledronic Acid in Preventing Collapse of the Osteonecrotic Femoral Head

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.

Study Overview

• Status: Completed
• Conditions: Avascular Necrosis of Femoral Head
• Intervention / Treatment: Drug: zoledronic acid (aclasta)

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.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Seongnam-Si, Gyeonggi-do, Korea, Republic of, 463-707
      • Seoul National University Bundang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: control; control group
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 Names: aclasta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Femoral Head Collapse Within 24 Months	Measurements were done at 6, 12, 24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Collpase Rate of Femoral Head	Measurement will be done at 0m, 3m, 6m, 9m, 12m, 18m, 24m)
Change of HHS (Harris Hip Scores), WOMAC Score, SF-36	Measurement will be done at 0m, 3m, 6m, 9m, 12m, 18m, 24m)
Time to Collapse of Femoral Head	Measurement will be done at 0m, 3m, 6m, 9m, 12m, 18m, 24m)
Time to Total Arthroplasty or Joint Preserving Surgery	Measurement will be done at 0m, 3m, 6m, 9m, 12m, 18m, 24m)

Collaborators and Investigators

• Sponsor: Seoul National University Bundang Hospital
• Collaborators: Novartis Korea Ltd.
• Investigators: Principal Investigator: Kyung-Hoi Koo, Professor, Seoul National University Bundang Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: July 14, 2009
• First Submitted That Met QC Criteria: July 14, 2009
• First Posted (Estimate): July 15, 2009

Study Record Updates

• Last Update Posted (Estimate): July 2, 2015
• Last Update Submitted That Met QC Criteria: June 7, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: bisphosphonate; avascular necrosis of femoral head; collapse
• Additional Relevant MeSH Terms: Pathologic Processes; Musculoskeletal Diseases; Bone Diseases; Osteonecrosis; Shock; Necrosis; Femur Head Necrosis; Physiological Effects of Drugs; Bone Density Conservation Agents; Zoledronic Acid
• Other Study ID Numbers: CZOL446HKR08T