Study Comparing Ibandronate Versus Placebo in Hip Osteonecrosis
Information source: University of Lausanne Hospitals
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Aseptic;; Hip Necrosis
Intervention: ibandronate (Drug); Placebo (Drug)
Phase: Phase 3
Status: Recruiting
Sponsored by: Brigitte Jolles, MD Official(s) and/or principal investigator(s): Bérengère Aubry-Rpzier, Dr, Study Director, Affiliation: Lausanne University Hospital
Overall contact: Bérengère Aubry-Rozier, Dr, Phone: +41 (0)21 314 5210, Email: berengere.aubry@chuv.ch
Summary
Aseptic osteonecrosis of the hip (AOH) concern 1 Swiss young adult to 1000 (30-40 years
old). They are responsible to a severe joint destruction and in the majority of cases a
joint replacement. To the hip, we can distinguish 4 stages of osteonecrosis according to
Ficat: 1, 2, 3, 4. Stage 3 and 4 AOH management are unanimous surgical. But management of
stage 1 and 2 are unclear. Bisphophonates are mainly used for bone and osteoporosis
diseases. They decrease the bone turn over, and the risk of fracture. They also decrease the
bone marrow oedema and the pain associated to this oedema. Ibandronate is a bisphosphonate
with a rapid effect, a short half-life, easy to manage, and with few side effects. We
designed a double-blind prospective randomized trial aiming to evaluate the efficacy of an
infusion of ibandronate versus placebo on pain and AOH progression in patients with stage 1
and 2 AOH. Our hypothesis is that there will be a pain reduction >=20 mm on the VAS scale
(SD 10mm) in the ibandronate group versus placebo, and a non radiological progression in the
treated group.
Clinical Details
Official title: Double Blind Randomized Study Comparing Ibandronate Versus Placebo in Hip Osteonecrosis Stage 1 and 2
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Primary outcome: VAS painImagery assessment
Secondary outcome: The Western Ontario and McMaster Universities Arthritis Index (Womac scale)Gait Analysis Hip Harris score Health-related quality of life EQ5D questionnaire
Detailed description:
Aseptic osteonecrosis of the hip (AOH) concern 1 Swiss young adult to 1000 (30-40 years
old). They are responsible to a severe joint destruction and in the majority of cases a
joint replacement. AOH represented 10% of the hip replacement in Switzerland. It could be
multiple. In this situation, they can be associated with a specific disease, justifying more
collaboration between surgeon and specialist on bone diseases or rheumatologist.
Initially patient with AOH presents mechanical pain and dysfunction. Either surgeon or
rheumatologist can suspect the diagnosis. To the hip, we can distinguish 4 stages of
osteonecrosis according to Ficat: 1, 2, 3, 4. The unfavourable evolution to a worst stage is
common and depend on the necrosis surface: less than 10% at 3 years if the surface is
small, 25% if the surface is moderate, 84% if the surface is extended. In case of
fortuitous discovery, natural evolution to the collapse from stage 1 is 55%, from stage 2
56% and from stage 3 96% with a median time of 39 months.
Mainly, in case of early Ficat stage (1), the final diagnosis is supported by a specific
image on MRI. It could be confounding with a differential diagnosis of transient
osteoporosis. Stage 3 and 4 AOH management are unanimous surgical. But management of stage 1
and 2 are unclear. Based on the physiopathology, associating 2 hypothesis (one vascular, one
osseous), bisphosphonates could be interesting to decrease the pain and the bone defect whom
evaluated to a joint collapse.
Bisphophonates are mainly used for bone and osteoporosis diseases. They decrease the bone
turn over, and the risk of fracture. They decrease the bone marrow oedema and the pain
associated to this oedema. Ibandronate is a bisphosphonate with a rapid effect, a short
half-life, easy to manage, and with few side effects.
Regarding these considerations, a study gathering surgeons, specialist in bone diseases and
radiologist is necessary. An interdisciplinary approach is needed to increase the knowledge
in this pathology and to well manage patients. The exact diagnosis of AOH needs a radiologic
expertise, the well management of movement and staging evolution needs an orthopaedic
management, the deliverance of treatment and bone efficacy of it needs a bone diseases
expertise.
A prospective randomized double blind with placebo study was designed. All consecutive
patients (18-50 yo) seen in OTP and RHU/CMO units of the CHUV with a confirmed diagnosis of
a single stage 1 or 2 according to Ficat AOH by an MRI could be included. After informed and
signed consent, they will be randomized to receive either placebo or 3 mg of ibandronate.
Infusion will be performed in 15 minutes. Size effect (pain VAS, Harris, Womac, EQ5D, gait
parameters, blood analysis) and side effects will be record at day 3, 7, month 1, 3, and 6.
If a patient has a persistent pain (same or worse VAS) at M3, a second infusion will be
performed, only with ibandronate.
At M1 and M3 an MRI will be performed to confirm the stage 1 (DD transient osteoporosis)
only for the stage 1 previous diagnosed patients.
At M3 and M6 an X ray and an MRI will be performed for all patients to analyze the stage
progression.
The primary end point will be at M6 for pain VAS and radiological progression. Patients who
need a second infusion at 3 months would be considered as not survival.
We hypothesize a reduction of 20 mm on the VAS scale (SD 10mm) in the ibandronate group
versus placebo, and a non radiological progression in the treated group. With a power to 90%
and an alpha of 0. 05 we want to include 50 patients. Drugs: Patients will be allowed to have
pain killers or NSAI prescribe by the investigator or the GP. All drugs have to be noted in
the diary. All patients will receive a physiotherapy prescription of one treatment per week,
over a period of 3 months. Moreover, the patient may freely choose any physiotherapist. The
prescription will be given by the investigator. Furthermore, the sessions can be spaced out
during the last three months, at the investigators discretion. On one hand participants will
be asked to not overwork. On other hand, participants will be asked to not adapt a non
weight-bearing status either.
From the economical point of view, looking at the CHUV scale only, 10% of the hip
arthroplasties made for AOH means 30 patients each year. If the treatment allows postponing
10 years the need of an arthroplasty as one study published with a lower methodology
suggests, it means an economy of CHF 1'200'000 each year.
Eligibility
Minimum age: 18 Years.
Maximum age: 50 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Signed consent form
- Male and female between 18 - 50 years old
- AOH stage 1 or 2 according to Ficat
- Pain VAS scale >40 mm (0-100)
Exclusion Criteria:
- Specific aetiology of AOH already known
- Cardiac and lung uncontrolled diseases
- Active malignancy untreated
- Hyper sensibility or allergy already known to ibandronate
- Pregnancy or breast feeding
- Severe kidney insufficiency (cl<30 ml/min)
- Contra-Indications to an MRI (Pacemaker, cochlear implant...)
Locations and Contacts
Bérengère Aubry-Rozier, Dr, Phone: +41 (0)21 314 5210, Email: berengere.aubry@chuv.ch
Lausanne University Hospital, Lausanne, Vaud 1005, Switzerland; Recruiting Bérengère Aubry-Rozier, Dr, Phone: +41 (0)21 314 5210, Email: berengere.aubry@chuv.ch Bérengère Aubry-Rozier, Dr, Principal Investigator Brigitte M Jolles, Professor, Principal Investigator
Additional Information
Starting date: June 2014
Last updated: June 3, 2015
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