Losartan to Improve Hip Microfracture

Phase 2TerminatedNCT04212650

Steadman Philippon Research Institute1 enrolled

Overview

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.

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Hip Osteoarthritis Hip Impingement Syndrome Cartilage Damage Fibrosis

Interventions

LosartanDRUG

Losartan will be administered to improve the quality of hip cartilage repair following arthroscopic microfracture. Losartan is a known anti-fibrotic agent via blocking of TGF-B1.

PlaceboOTHER

Appearance-matched microcrystalline cellulose placebo

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 Years

Medical Language ↔ Plain English

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

Locations (1)

Steadman Philippon Research Institute

Vail, Colorado, United States

Outcomes

Primary Outcomes

Incidence of Treatment-Emergent Adverse Events

Occurrence of treatment-emergent adverse events

Time frame: 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

Patient Reported Outcomes Questionnaire

12-question Short-Form General Health Survey (SF-12) - Including Physical Component Summary (PCS) and Mental Component Summary (MCS). * Higher score represents greater health. * Scale standardized to a US Population mean of 50 and standard deviation of 10 points.

Time frame: Baseline, 3 months, 6 months, 12 months and 18 months

Patient Reported Outcomes Questionnaire - Patient Satisfaction

Patient Satisfaction * Scale from 1-10. * Higher score represents greater patient satisfaction.

Time frame: Baseline, 3 months, 6 months, 12 months and 18 months

Patient Reported Outcomes Questionnaire - Harris Hip Score

Harris Hip Score (HHS). * Scale from 0-100. * Higher score represents greater hip health.

Time frame: Baseline, 3 months, 6 months, 12 months and 18 months

Patient Reported Outcomes Questionnaire - Hip Outcome Score

Hip Outcome Score (HOS) - Including Sport and Activities of Daily Living (ADL) subscales. * Scale from 0-100. * Higher score represents greater hip health.

Time frame: Baseline, 3 months, 6 months, 12 months and 18 months

Patient Reported Outcomes Questionnaire - Western Ontario and McMaster Universities Osteoarthritis Index

Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) - Including Pain, Stiffness and Physical Function subscales. * Scale from 0-96. * Higher score represents worse hip health.

Data from ClinicalTrials.gov

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