Clinical trial NCT04212650: Losartan to Improve Hip Microfracture
Official title: Biologically Regulated Marrow Stimulation by Blocking Fibrosis to Improve Cartilage Repair: A Randomized Double-Blind, Placebo-Controlled Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Hip Osteoarthritis
Hip Impingement Syndrome
Cartilage Damage
Fibrosis
Keywords: Cartilage Microfracture
Losartan
Transforming growth factor beta 1
Hip Arthroscopy
Lead sponsor: Steadman Philippon Research Institute
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
name: Office of Naval Research (ONR)
First posted: 2019-12-27
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Block Randomization
Primary purpose: TREATMENT

Brief summary: Phase I/IIA randomized, double-blind, placebo-controlled clinical trial to assess safety and efficacy of oral losartan for improving cartilage repair following microfracture to treat focal cartilage defects during hip arthroscopy.

Detailed description: This is a prospective, double-blind, placebo-controlled, randomized clinical trial that will be conducted at The Steadman Clinic and Steadman Philippon Research Institute.

Articular cartilage defects that extend full thickness to subchondral bone rarely heal without intervention. Some patients may not develop clinically significant problems from acute full-thickness chondral defects, but many eventually suffer from debilitating degenerative changes. Microfracture is the most commonly used first-line treatment technique for chondral lesions in the hip, however, this procedure's effectiveness is limited by the repair tissue being a hybrid of hyaline and fibrocartilage. We hypothesize that administration of a transforming growth factor beta 1 (TGF-β1) blocker, losartan (an approved hypertension drug, angiotensin II receptor antagonist) with microfracture will enhance articular cartilage repair as assessed on quantitative magnetic resonance imaging. We will also measure patient benefit through the recording of patient reported outcomes in the 18 months following surgery. The Division of Pulmonary, Allergy and Rheumatology Products within the Center for Drug Evaluation and Research at the Food and Drug Administration has granted an investigational new drug (IND) exemption to pursue this trial in accordance with 21 CFR 312.2(b).

Eligibility criteria: Inclusion Criteria:

* Underwent primary hip arthroscopy
* Underwent baseline quantitative MRI at The Steadman Clinic (TSC)
* Single, localized, grade 3 or 4 cartilage lesion of the acetabulum or femoral head treated with Bone Marrow Stimulation (BMS; i.e. microfracture)
* Aged 18-60 at time of surgery
* Tonnis grade 1 or less

Exclusion Criteria:

* Two or more cartilage lesions of grade 3 or 4
* Less than 2 mm of minimal hip joint space
* Osteoarthritis or diffuse change of cartilage
* Non-English speaking
* Prior hip surgery on operative hip
* Pre-existing bony deformity caused by previous fracture(s)
* Synovial chondromatosis
* Pigmented Villonodular Synovitis (PVNS)
* Dysplasia (center edge angle \<20 degrees)
* History of Avascular Necrosis (AVN), Perthes disease, or slipped capital femoral epiphysis (SCFE)
* Inflammatory arthritis or other arthritis caused by autoimmune disease
* Patients allergic to any active or inactive ingredient of losartan
* Patients taking medication with known losartan interaction, including phenobarbital, rifampin, and fluconazole.
* Subjects that are currently taking losartan

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: Drug related adverse events will be monitored during the medication phase (post-op days 2-31) and orthopaedic-related health and function will be monitored for the entire study duration (18 months).
Secondary outcomes:
measure: Patient Reported Outcomes Questionnaire
timeFrame: Baseline, 3 months, 6 months, 12 months and 18 months
measure: Patient Reported Outcomes Questionnaire - Patient Satisfaction
timeFrame: Baseline, 3 months, 6 months, 12 months and 18 months
measure: Patient Reported Outcomes Questionnaire - Harris Hip Score
timeFrame: Baseline, 3 months, 6 months, 12 months and 18 months
measure: Patient Reported Outcomes Questionnaire - Hip Outcome Score
timeFrame: Baseline, 3 months, 6 months, 12 months and 18 months
measure: Patient Reported Outcomes Questionnaire - Western Ontario and McMaster Universities Osteoarthritis Index
timeFrame: Baseline, 3 months, 6 months, 12 months and 18 months
measure: Patient Reported Outcomes Questionnaire - Tegner Activity Scale
timeFrame: Baseline, 3 months, 6 months, 12 months and 18 months
measure: Patient Reported Outcomes Questionnaire - Numeric Rating Scale for Pain
timeFrame: Baseline, 3 months, 6 months, 12 months and 18 months
measure: Morphological and Quantitative Magnetic Resonance Imaging (MRI)
timeFrame: Baseline and 12 months
measure: Physical Examination of the Hip - Strength
timeFrame: Baseline, 3 months, and 12 months
measure: Physical Examination of the Hip - Range of Motion
timeFrame: Baseline, 3 months, and 12 months
Other outcomes:
Locations:
city: Vail
country: United States
facility: Steadman Philippon Research Institute
state: Colorado
Study officials:
affiliation: Steadman Philippon Research Institute
name: Marc J Philippon, MD
role: PRINCIPAL_INVESTIGATOR
References: