Clinical trial NCT06003101: Effect of PRP, PPP, & BMAC on Functional Outcomes Following Hip Arthroscopy for Acetabular Labral Pathologies
Official title: Effect of Platelet-Rich Plasma, Platelet-Poor Plasma, & Bone Marrow Aspirate Concentrate Application on Functional Outcomes Following Hip Arthroscopy for Acetabular Labral Pathologies: A Prospective Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Acetabular Labrum Tear
Femoro Acetabular Impingement
Chondral Defect
Bone Marrow Aspirate Concentrate
Keywords: Acetabular Labrum Tear
Femoro Acetabular Impingement
Chondral Defect
Bone Marrow Aspirate Concentrate
Chondrolabral Junction
Osteoarthritis
Hip Arthroscopy
BMAC
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2023-08-21
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to assess the effect of PRP/PPP/BMAC application on functional outcomes after hip arthroscopy to address acetabular labral pathologies. The main questions it aims to answer are:

1. Does PRP/PPP/BMAC application improve functional outcomes after hip arthroscopy to address acetabular labral pathologies?
2. Does PRP/PPP/BMAC application reduce the arthritic burden as measured by functional outcomes following hip arthroscopy to address labral pathologies with concomitant PRP/PPP/BMAC application?

Detailed description: 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profound degenerative changes to the labral and adjacent articular cartilage, labral resection/debridement has largely been replaced by techniques that emphasize labral tissue and blood flow preservation (i.e., repair, augmentation, reconstruction) due to a growing body of evidence reporting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.

Eligibility criteria: Inclusion Criteria:

* Age: \> or equal to 18 years
* Clinically indicated for hip arthroscopy (by the study PI) to address a labral pathology
* Willingness to participate, amenable to randomization into either treatment arm of the research study, and the ability to understand \& sign the informed consent document

Exclusion Criteria:

* Non-English speaking (PROM surveys are only validated in English)
* Prior same site (i.e., ipsilateral hip) surgery, including but not limited to previous hip arthroscopy, core decompression, or periacetabular osteotomies

Primary outcomes:
measure: Pain Level
timeFrame: Baseline (pre-operative), 3 months, 6 months, 12 months, and 24 months
measure: Modified Harris Hip Score (mHHS)
timeFrame: Baseline (pre-operative), 3 months, 6 months, 12 months, and 24 months
measure: International Hip Outcome Tool-12 (iHOT-12)
timeFrame: Baseline (pre-operative), 3 months, 6 months, 12 months, and 24 months
measure: Non-Arthritic Hip Score (NAHS)
timeFrame: Baseline (pre-operative), 3 months, 6 months, 12 months, and 24 months
measure: Hip Outcome Score (HOS)
timeFrame: Baseline (pre-operative), 3 months, 6 months, 12 months, and 24 months
measure: Kerlan-Jobe Orthopaedic Clinic Athletic Hip Score
timeFrame: Baseline (pre-operative), 3 months, 6 months, 12 months, and 24 months
measure: Visual Analog Scale (VAS) Pain Score
timeFrame: Baseline (pre-operative), 3 months, 6 months, 12 months, and 24 months
Secondary outcomes:
measure: Oswestry Low Back Disability Questionnaire (aka Oswestry Disability Index, ODI)
timeFrame: Baseline (pre-operative), 3 months, 6 months, 12 months, and 24 months
measure: Tegner Lysholm Knee Scoring Scale
timeFrame: Baseline (pre-operative), 3 months, 6 months, 12 months, and 24 months
measure: Patient-Reported Outcomes Measurement Information System-10 (PROMIS-10)
timeFrame: Baseline (pre-operative), 3 months, 6 months, 12 months, and 24 months
measure: The Pittsburgh Sleep Quality Index (PSQI):
timeFrame: Baseline (pre-operative), 3 months, 6 months, 12 months, and 24 months
measure: Patient Satisfaction, Postoperative Protocol Compliance, & Subsequent Surgeries
timeFrame: Baseline (pre-operative), 3 months, 6 months, 12 months, and 24 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Scott D. Martin, MD
role: PRINCIPAL_INVESTIGATOR
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