Efficacy of Zoledronic Acid in Preventing Collapse of the Osteonecrotic Femoral Head

Avascular Necrosis of Femoral Head Clinical Trial

— EZAPCOFH  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00939900
• Other study ID #: CZOL446HKR08T
• Status: Completed
• Phase: Phase 3
• First received: July 14, 2009
• Last updated: June 7, 2015
• Start date: July 2009
• Est. completion date: June 2012

Study information

• Verified date: June 2015
• Source: Seoul National University Bundang Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationKorea: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Avascular Necrosis of Femoral Head
• Femur Head Necrosis
• Necrosis
• Osteonecrosis

Intervention

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

Locations

Country	Name	City	State
Korea, Republic of	Seoul national University Bundang Hospital	Seongnam-Si	Gyeonggi-do

Sponsors (2)

Lead Sponsor	Collaborator
Seoul National University Bundang Hospital	Novartis Korea Ltd.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Femoral Head Collapse Within 24 Months		Measurements were done at 6, 12, 24 months	Yes
Secondary	Collpase Rate of Femoral Head		Measurement will be done at 0m, 3m, 6m, 9m, 12m, 18m, 24m)	Yes
Secondary	Change of HHS (Harris Hip Scores), WOMAC Score, SF-36		Measurement will be done at 0m, 3m, 6m, 9m, 12m, 18m, 24m)	Yes
Secondary	Time to Collapse of Femoral Head		Measurement will be done at 0m, 3m, 6m, 9m, 12m, 18m, 24m)	Yes
Secondary	Time to Total Arthroplasty or Joint Preserving Surgery		Measurement will be done at 0m, 3m, 6m, 9m, 12m, 18m, 24m)	Yes