Losartan to Improve Hip Microfracture

Sponsor

Steadman Philippon Research Institute (Other)

Overall Status

Terminated

CT.gov ID

NCT04212650

Collaborator

United States Department of Defense (U.S. Fed), Office of Naval Research (ONR) (U.S. Fed)

Enrollment

Location

Arms

10.6

Actual Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hip Osteoarthritis Hip Impingement Syndrome Cartilage Damage Fibrosis	Drug: Losartan Other: Placebo	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

1 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Block RandomizationBlock Randomization

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Biologically Regulated Marrow Stimulation by Blocking Fibrosis to Improve Cartilage Repair: A Randomized Double-Blind, Placebo-Controlled Study

Actual Study Start Date :

Jan 16, 2020

Actual Primary Completion Date :

Dec 4, 2020

Actual Study Completion Date :

Dec 4, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Losartan 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. Other Names: Losartan Potassium
Placebo Comparator: Placebo Appearance-matched placebo capsules, oral administration, twice daily, taken for 30 consecutive days starting on the evening of the second post-surgery day.	Other: Placebo Appearance-matched microcrystalline cellulose placebo

Arm

Intervention/Treatment

Experimental: 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.

Drug: Losartan

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.

Other Names:

Losartan Potassium

Placebo Comparator: Placebo

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

Other: Placebo

Appearance-matched microcrystalline cellulose placebo

Outcome Measures

Primary Outcome Measures

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 adverse events

Secondary Outcome Measures

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 [Baseline, 3 months, 6 months, 12 months and 18 months]
Patient Satisfaction Scale from 1-10. Higher score represents greater patient satisfaction.
Patient Reported Outcomes Questionnaire [Baseline, 3 months, 6 months, 12 months and 18 months]
Harris Hip Score (HHS). Scale from 0-100. Higher score represents greater hip health.
Patient Reported Outcomes Questionnaire [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 [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 [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 [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.
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.
Physical Examination of the Hip [Baseline, 3 months, and 12 months]
Standard physical exam assessment of hip strength, measured in Newtons.
Physical Examination of the Hip [Baseline, 3 months, and 12 months]
Standard physical exam assessments of hip range of motion (ROM), measured in degrees.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts 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