1. Background Surgical management of labral pathology has evolved to reflect our
current understanding of mechanism of injury and resulting hip dysfunction.
Correction of labral pathology presents a technical challenge, and many techniques
currently exist. Initial management of labral tears included complete resection or
debridement to the bony acetabular surface of the affected region. This had the
advantage of acutely reducing hip pain but was later shown by seminal biomechanical
studies to compromise the mechanical integrity of the hip. With the exception of
cases found to have profound degenerative changes to the labral and adjacent
articular cartilage, labral resection/debridement has largely been replaced by
techniques that emphasize labral tissue and blood flow preservation (i.e., repair,
augmentation, reconstruction) due to a growing body of evidence reporting improved
functional outcomes.
Repair techniques focus on restoring functional anatomy by re-establishing the
labrum's native position and contour on the rim of the acetabulum. Similar to
repairing a torn meniscus in the knee, restoring the anatomic footprint of a torn
labrum will reconstitute normal joint biomechanics. Labral injuries are often seen
in the setting of femoroacetabular impingement and are a common source of early
symptomatology. Therefore, during labral repair, concomitant correction of bony cam
lesions, pincer lesions, or both may be necessary to prevent reinjury of the labrum.
Correction of cam and pincer lesions requires femoral neck osteoplasty (trimming of
femoral neck) and acetabuloplasty (trimming of the bony acetabular rim),
respectively.
Articular cartilage has limited intrinsic healing capacity and pathology frequently
results in gradual and progressive tissue deterioration. Moreover, many patients
presenting with hip pain in the third and fourth decade of life already have
osteoarthritic changes observed at the time of arthroscopy. It has been proposed
that altered biomechanics of the hip resulting from a labral tear can increase the
stresses through the hip causing faster progression of cartilage wear. Moreover,
previous literature has illustrated the significant association between patients
with moderate to severe osteoarthritis undergoing hip arthroscopy and inferior
postoperative outcomes when compared to similar patients with less osteoarthritis.
Thus, while there have been notable advances in acetabular labral repair techniques,
there continues to be demand for an innovation that can preserve the acetabular
cartilage and chondrolabral junction in order to improve outcomes in these patients.
Recently, given the properties of the isolated components, bone marrow aspirate
concentrate (BMAC) has gained attention for its theoretical potential to treat OA
and slow the progression of cartilage deterioration. BMAC contains marrow elements
including mesenchymal stromal cells (MSCs), platelets, red and white blood cells,
and hematopoietic precursors. Bone-marrow derived platelets contain growth factors,
cytokines, and chemokines, which can promote wound healing, collagen synthesis,
suppression of pro-inflammatory cytokines, production of extracellular matrix, and
chondrocyte proliferation. MSCs are multipotent, non-hematopoietic stromal cells
with the capacity to self-renew, proliferate, and differentiate into cartilage,
bone, or fat. Numerous tissue sources can be used to isolate MSC cells, including
bone marrow, adipose tissue, synovial membrane, bursa, umbilical cord blood, and
periosteum. Within orthopaedic procedures, bone marrow derived MSCs (BMSCs) have
been reported to be an excellent source of MSCs and are often harvested from the
iliac crest, distal femur, proximal humerus, and vertebrae.
Currently, the PI has adopted the use of a combined mixture of platelet-rich plasma
(PRP), platelet-poor plasma (PPP), and BMAC that are harvested, processed, and
applied during arthroscopic acetabular labral repair as his standard of care when
encountering mild to moderate cartilage damage, chondrolabral junction breakdown,
and isolated chondral lesions/flaps. Previous studies performed by the PI have
demonstrated that harvesting bone marrow aspirate from the body of the ilium is not
only a safe procedure, but also provides a concentration of connective tissue
progenitor cells that is comparable to other harvest sites in the body. Furthermore,
harvesting bone marrow aspirate from the body of the ilium concomitantly with
arthroscopic acetabular labral repair is efficient, limits the harvesting and repair
of the labrum to one procedure, and limits the procedure to only one procedural
site. Regarding clinical outcomes, the PI recently published a foundational study
that demonstrated that augmenting the acetabular labral repair site with bone marrow
aspirate concentrate harvested from the body of the ilium resulted in significantly
greater functional improvements in patients with moderate osteoarthritis compared to
similar patients without BMAC application. Additionally, Kucharik et al. reported
that patients with full-thickness chondral flaps treated with BMAC at the time of
arthroscopic labral repair, compared to microfracture, experienced significantly
greater improvements in functional outcomes at 12 months follow-up. Thus,
demonstrating the possible benefits and potential of BMAC application during
arthroscopic labral repair in the first randomized controlled trial (RCT) is
necessary.
The investigators are proposing the initiation of RCT) to provide Level I evidence
for the investigation of the effect of PRP/PPP/BMAC application during arthroscopic
acetabular labral repair. The RCT will compare postoperative outcomes between
subjects that do and do not receive PRP/PPP/BMAC application during hip arthroscopy
for acetabular labral pathologies using current, evidence-based, standard of care
techniques. The outcomes of this study have the potential to fundamentally change
the practice of hip arthroscopy across the world and lead to the improvement of
countless lives. From an administrative perspective, this study could also result in
future insurance coverage for the PRP/PPP/BMAC harvesting/processing/application
procedure
- - something that is unlikely to occur from retrospective studies alone.
On
the other hand, if this study yields evidence that BMAC does not significantly
improve the functional outcomes of patients undergoing hip arthroscopy for
acetabular labral repair, it will provide critical insight to prevent patients from
undergoing an additional procedure that confers minimal or no benefit at an
additional cost.
2. Specific Aims and Objectives Study Aim 1: To assess the effect of PRP/PPP/BMAC
application on functional outcomes after hip arthroscopy to address acetabular
labral pathologies.
Hypothesis 1.1: Subjects treated with BMAC will have significantly improved
patient-reported outcome measures (PROMs) at 12 months compared to baseline.
Hypothesis 1.2: Subjects treated without BMAC will have significantly improved PROMs
at 12 months compared to baseline.
Hypothesis 1.3: Subjects treated with BMAC will have significantly greater
improvements in PROMs compared to subjects who did not receive BMAC application at
12 months compared to baseline.
Hypothesis 1.4: Hypothesis 1.1-1.3 will hold true at 24 months and beyond.
Study Aim 2: To evaluate the effect of arthritic burden on functional outcomes
following hip arthroscopy to address labral pathologies with concomitant
PRP/PPP/BMAC application.
Hypothesis 2.1: Subjects with severe osteoarthritis (Outerbridge Grade 4, graded
arthroscopically) will have inferior PROMs improvements 12 months after arthroscopic
treatment of labral pathology without PRP/PPP/BMAC application, as compared to
similar subjects with less severe osteoarthritis (Outerbridge Grade < or equal to
3).
Hypothesis 2.2: Subjects with severe osteoarthritis (Outerbridge Grade 4, graded
arthroscopically) will have inferior PROMs improvements 12 months after arthroscopic
treatment of labral pathology with PRP/PPP/BMAC application, as compared to similar
subjects with less severe osteoarthritis (Outerbridge Grade < or equal to 3).
Hypothesis. 2.3: Hypothesis 2.1-2.3 will hold true at 24 months and beyond.
Exploratory Hypothesis: Subjects with moderate osteoarthritis (Outerbridge Grade
2-3) treated with PRP/PPP/BMAC application will have significantly greater
improvements in PROMs compared to similar subjects who did not receive PRP/PPP/BMAC
application.
3. General Description of Study Design Single-blind, prospective randomized controlled
trial (RCT) of patients with acetabular labral pathologies undergoing hip
arthroscopy comparing outcomes of subjects receiving treatment of the labrum alone
versus subjects receiving treatment of the labrum with concomitant PRP/PPP/BMAC
application. Regardless of treatment allocation, no alterations will be made to the
PI's surgical technique, including but not limited to initial portal placement,
capsular management, addressment of the labral lesions (i.e., debridement, repair,
augmentation, reconstruction), or the need to perform femoral and/or acetabular
osteoplasties.
Subjects with symptomatic acetabular labral pathologies and clinically indicated for
surgical intervention will be appropriately consented for hip arthroscopy by the PI. The
PI routinely discusses his use of PRP/PPP/BMAC application and will briefly mention that
this intervention is available, if clinically indicated during the time of surgery.
Following the surgical consenting process, potential subjects will be introduced to the
study by a member of the research team. Patients not interested in participating in the
study may still be offered PRP/PPP/BMAC application but will be informed that the
associated cost/hospital charge must be covered out-of-pocket (i.e., direct cost to
patient). Patients interested and willing to participate in the study will have their
surgical consents verified to include the possible application of PRP/PPP/BMAC.
Subjects will be tracked using validated patient-reported outcomes measures (PROMs
- - see
below), along with review of the medical record for physical exam and
radiographic/advanced imaging findings to track their progress throughout the study and
will continue for as long as they are a patient of the PI.
Study procedures will be
complete when the last enrolled subject completes 20-year follow-up and completes the
corresponding surveys.
Subjects will undergo the procedure under general anesthesia and will be positioned
supine on a hip distraction table. Following portal placement and establishing
intra-articular access, the PI will evaluate the extent of damage and tissue quality of
the labrum, chondral surfaces, transition zone cartilage, and chondrolabral junction
intraoperatively, under direct arthroscopic visualization.
For patients with limited damage or degenerative changes to the labrum, articular
surfaces, transition zone cartilage, and chondrolabral junction, the procedure will be
carried out in standard fashion (void of any study-specific intraoperative
procedures/interventions)
- - as PRP/PPP/BMAC application is not clinically indicated in
these patients.
These patients that do not meet the clinical indications for PRP/PPP/BMAC
application will be stratified into a tertiary cohort to serve as 'controls'
(randomization will not apply to these patients), but will continue to receive subsequent
surveys via REDCap to track their functional progress and outcomes.
Conversely, for patients with evidence of damage or degenerative changes to the labrum
(i.e., Beck Labral Tear Classification ≥ 1), articular surfaces (i.e., Outerbridge Grade
≥ 2), transition zone cartilage (i.e., ALAD Classification ≥ 2), and/or chondrolabral
junction (i.e., Beck Chondrolabral Junction Classification ≥ 1), subsequent treatment
will be dependent on their treatment allocation (outlined below). Patients will be
randomized into treatment arms using a computer algorithm.
- - NO TREATMENT Arm: Patients will undergo hip arthroscopy for the treatment of their
labral pathology.
- - TREATMENT Arm: Patients randomly allocated to receive BMAC will undergo hip
arthroscopy and will receive PRP/PPP/BMAC application through the PI's standardized
method of harvest, processing, and application.
Notably, bone marrow aspiration from the body of the ilium will be performed through one
of the arthroscopic portals. In certain situations, pending anatomical constraints, an
additional arthroscopic portal may be created to safely harvest bone marrow. However,
given the normal variation in the number of arthroscopy portals created, it would be
unknown to the patient, thus blinded, to whether bone marrow was harvested.
Additionally, as outlined in the informed consent document, patients will be blinded to
what treatment arm they are randomized to avoid confounding the results of the PROMs they
complete. Regardless of research study arm, patients will be blinded to the treatment
they receive during the study period.
This off-label* use of PRP/PPP/BMAC application during hip arthroscopy has been adopted
to become the PI's standard of care to date. However, to date, it has not been proven to
be superior to the absence of its use in clinical practice, and thus it is being
investigated as a research-specific intervention in comparison to standard of care hip
arthroscopy without PRP/PPP/BMAC. Upon initiation of this proposed RCT, the PI's research
fund will pay for the associated costs of the PRP/PPP/BMAC procedure if subjects are
enrolled and randomized into the treatment arm of this present study. Patients that wish
to receive PRP/PPP/BMAC application during their hip arthroscopy (if clinically indicated
intraoperatively
- - upon arthroscopic visualization/assessment of the labrum/chondral
surfaces/chondrolabral junction), but are not amenable to randomization/study enrollment,
may opt to pay for this intervention out-of-pocket (i.e., direct charge to the patient).
By agreeing to participate in this RCT, subjects will be consenting to:
- - Be randomized into a treatment arm that either will or will not receive PRP/PPP/BMAC
application, if clinically indicated at the time of surgery.
- - Agree to be 'blinded' to their assigned treatment allocation (i.e., subjects will
not be told what treatment group they were randomized to)
- Agree to complete outcome and PROM surveys prior to surgery and at regularly
scheduled intervals up until 20 years postoperatively.
- - Agree to be contacted via email/phone by the study team for survey distribution,
follow up with questions about survey responses, and possible reminders about survey
completion.
- - The PRP/PPP/BMAC application technique is in accordance with the Federal Drug
Administrations' (FDA) guidelines/considerations under section 361 of the
Public Health Service (PHS) Act and Title 21 Code of Federal Regulations (CFR)
Part 1271 for criterion of minimal manipulation and homologous use.
Thus, the
difference between un-enrolled patients and enrolled study participants is the
possibility (pending randomization) for of PRP/PPP/BMAC harvest, processing,
and application. Outside of the study, patients may request PRP/PPP/BMAC
application during hip arthroscopy with Dr. Martin. However, these patients
will be responsible for the associated out-of-pocket costs of the procedure if
Dr. Martin deems PRP/PPP/BMAC application to be clinically indicated.
