Losartan to Improve Hip Microfracture

Phase 1

Terminated

• Conditions: Hip Impingement Syndrome; Fibrosis; Hip Osteoarthritis; Cartilage Damage
• Interventions: Drug: Losartan; Other: Placebo

• Registration Number: NCT04212650
• Lead Sponsor: Steadman Philippon Research Institute

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).

Study Timeline

• Study First Submitted: 2019-12-19
• Study First Submitted QC: 2019-12-24
• Study First Posted: 2019-12-27
• Study Start: 2020-08-07
• Primary Completion: 2020-12-04
• Study Completion: 2020-12-04
• Results First Submitted: 2023-06-26
• Status Verified: 2023-10
• Results First Submitted QC: 2023-10-25
• Last Update Submitted: 2023-10-25
• Results First Posted: 2023-10-30
• Last Update Posted: 2023-10-30

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events	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).	Occurrence of treatment-emergent adverse events

Secondary Outcome Measures

Name	Time	Method
Patient Reported Outcomes Questionnaire - Patient Satisfaction	Baseline, 3 months, 6 months, 12 months and 18 months	Patient Satisfaction; * Scale from 1-10.; * Higher score represents greater patient satisfaction.
Physical Examination of the Hip - Range of Motion	Baseline, 3 months, and 12 months	Standard physical exam assessments of hip range of motion (ROM), measured in degrees.
Patient Reported Outcomes Questionnaire	Baseline, 3 months, 6 months, 12 months and 18 months	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.
Patient Reported Outcomes Questionnaire - Hip Outcome Score	Baseline, 3 months, 6 months, 12 months and 18 months	Hip Outcome Score (HOS) - Including Sport and Activities of Daily Living (ADL) subscales.; * Scale from 0-100.; * Higher score represents greater hip health.
Patient Reported Outcomes Questionnaire - Western Ontario and McMaster Universities Osteoarthritis Index	Baseline, 3 months, 6 months, 12 months and 18 months	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.
Patient Reported Outcomes Questionnaire - Tegner Activity Scale	Baseline, 3 months, 6 months, 12 months and 18 months	Tegner Activity Scale; * Scale from 0-10.; * Higher score represents greater activity level.
Patient Reported Outcomes Questionnaire - Numeric Rating Scale for Pain	Baseline, 3 months, 6 months, 12 months and 18 months	Numeric Rating Scale (NRS) for Pain; * Scale from 1-10.; * Higher score represents greater pain.
Physical Examination of the Hip - Strength	Baseline, 3 months, and 12 months	Standard physical exam assessment of hip strength, measured in Newtons.
Morphological and Quantitative Magnetic Resonance Imaging (MRI)	Baseline and 12 months	Cartilage quality assessed by blinded radiologist using morphological MRI. Quantitative MRI using T2 mapping images with texture analysis used to assess water content and collagen organization within the cartilage and surrounding tissue.
Patient Reported Outcomes Questionnaire - Harris Hip Score	Baseline, 3 months, 6 months, 12 months and 18 months	Harris Hip Score (HHS).; * Scale from 0-100.; * Higher score represents greater hip health.

Trial Locations

Locations (1)

Steadman Philippon Research Institute; 🇺🇸 Vail, Colorado, United States