Post-Market Data Collection for Treatment of Avascular Necrosis (AVN) of the Femoral Head With Core Decompression Using the PerFuse Instrument and BioCUE

Avascular necrosis (AVN) is a disease that affects weight bearing joints, most
commonly, the hip (Gangji & Hauzeur, 2010). AVN of the femoral head is
associated with chronic or high dose corticosteroid use, alcohol abuse, trauma,
sickle-cell disease, organ transplant, smoking and chronic diseases such as
renal disease, hematologic disease, inflammatory bowel disease, systemic lupus
erythematosus and HIV. AVN of the femoral head typically presents between the
ages of 20 and 40 (Gangji et al., 2010). Left unchecked, AVN of the femoral
head can lead to collapse and the need for total hip arthroplasty (THA). Due to
the young to middle-aged patient population, a joint saving procedure that
prevents or postpones THA is needed. This is especially true for patients with
sickle cell disease as 90% of those with AVN experience femoral head collapse
within 2 years of diagnosis and also tend to have higher failure rates and
complications with THA (Neumayr et al., 2006). Current options to halt the
progression of AVN include core decompression, osteotomy and medications
however up to 40% of patients continue to progress to THA.

Core decompression (CD) has been used for several decades as a joint-preserving
method to decrease pressure and pain in the necrotic lesion (Koo et al., 1995)
and is the most common treatment for pre-collapse AVN (McGrory et al., 2007).
In patients with AVN, it is thought that there is a lack of progenitor cells in
the location of the femoral head and proximal femur making the body unable to
heal the lesion. In order to improve the outcomes, CD has been combined with
the injection of stem cells obtained from bone marrow aspirate to re-populate
the lesion with host progenitor cells. (Houdek, Wyles, Martin, & Sierra, 2014)

Several studies have been completed in cohorts of varying size showing
promising results with biologically assisted CD (Tabatabaee, Saberi, Parvizi,
Mortazavi, & Farzan, 2015). This study will evaluate the performance of
biologically assisted CD performed with the PerFuse instrument and output from
the BioCUE Concentration System. PerFuse features a small (6 mm) cannula
advanced with a mallet for decompression of the lesion which allows for
post-operative weight bearing. There is no need to decompress with a reamer
which can heat the tissues potentially causing damage.

The objective of the study is to characterize the performance of biologically
assisted core decompression performed with the PerFuse instrument and BioCUE
for the treatment AVN of the femoral head. The study will explore the potential
impact of patient demographics and baseline characteristics on treatment
outcome. In addition, the utilization of healthcare resources and associated
costs will be investigated in treated patients.

This multicenter, observational study will be executed in up to 10 centers in
the United States and Europe. A maximum of 100 patients will be included.
Patients with avascular necrosis (AVN) in the femoral head meeting the
eligibility criteria will be invited to participate in the study.
Participating patients will undergo the procedure as per Instructions for Use
of the PerFuse instrument and the BioCUE Concentration System (CE marked,
within label). Patients may undergo up to two procedures per hip, but the
initial procedure will remain the index for the follow-up scheme. Patients will
be followed-up for 60 months, and questionnaires will be completed at 3, 6, 12,
24, 36, 48 en 60 months after the initial procedure.
The patients will be followed in the study until one of the following study
completion criteria occur:
- Invasive procedure other than study procedure required
- Completion of 60 months of follow-up after the initial procedure
- Death, Withdrawal or Lost to follow-up

The study procedure will be performed in accordance with the geographical
location
specific surgical technique described in Appendix 2 and in accordance with the
geographical location specific Manufacturer*s Instructions For Use (IFU)
(Appendix 1) with one exception for European sites. European sites will use
three
standard BioCUE tubes instead of two standard BioCUE tubes plus one standard
GPS III tube.

A rehabilitation protocol will occur per standard of care protocol at the
participating
center and details of this protocol will be documented in order to evaluate the
effect
of the post-procedure care and rehabilitation protocol on the outcome of the
treatment.

According to the standard of care in this center patients can choose to be
treated with the PerFuse-system and BioCUE even without participation in this
study. Risks associated with these commercially available devices are described
in the Instructions for Use. Since the PerFuse and BioCUE are used as standard
of care in this center, these risks are not additional risks as a result of
study participation.

If a patient participates in the study, besides the study treatment and the
standard MRI, the patient will be asked to complete some questionnaires at
predefined time points over a period of 60 months. Additionally, at 12 months
after the procedure an extra MRI will be taken for the study. The
questionnaires can be completed by phone or online or in the hospital. The
patient will be asked to visit the hospital one additional time compared to the
standard procedure for the extra MRI.

The additional risks and burden due to participation in the study consist of
discomfort when answering some of the questions on the surveys, and risks
associated with MRI.

Risks associated with MRI imaging are the following:
- The magnetic field used by MRI scanners may cause malfunction or heat up of
implanted
- medical devices that contain metal during the exam.
- Any loose metal object may cause damage or injury if it gets pulled toward
the magnet.
- Dyes from tattoos can cause skin irritation after an MRI exam.
- Medication patches can cause skin burns.
- Prolonged exposure to radio waves during the scan could lead to slight
warming of the body
- but this is rare.
- Patients may have some anxiety due to being in a confined space.

The MRI technician will help the patient to minimize the risks as much as
possible. Taking MRIs is a standard procedure at the center.

Therefore, the opinion of the sponsor is that the risk due to study
participation are negligible.