Losartan to Improve Hip Microfracture

Steadman Philippon Research Institute

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Hip Osteoarthritis; Hip Impingement Syndrome; Cartilage Damage; Fibrosis

Treatments: Other: Placebo; Drug: Losartan

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT04212650

2019-15

Details and patient eligibility

About

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.

Full 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).

Enrollment: 1 patient

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1 participants in 2 patient groups, including a placebo group

Losartan

Experimental group

Description:

12.5mg Losartan capsules, oral administration, twice daily (25mg total per day), taken for 30 consecutive days starting on the evening of the second post-surgery day.

Treatment:

Drug: Losartan

Placebo

Placebo Comparator group

Description:

Appearance-matched placebo capsules, oral administration, twice daily, taken for 30 consecutive days starting on the evening of the second post-surgery day.

Treatment:

Other: Placebo