MedPath

Mitigation of Arthrofibrosis After Total Knee Arthroplasty Using Losartan

Phase 1
Recruiting
Conditions
Knee Arthroplasty, Total
Interventions
Registration Number
NCT06108063
Lead Sponsor
Steadman Philippon Research Institute
Brief Summary

The purpose of this study is to evaluate the efficacy of Losartan use post-operatively for reducing or preventing the development of arthrofibrosis and the associated adverse impacts on clinical outcomes.

Detailed Description

This is a double-blind, randomized, placebo-controlled clinical trial proposed to evaluate the efficacy and safety of Losartan for reducing or preventing arthrofibrosis and improving patient-reported outcomes after total knee arthroplasty (TKA). Fibrosis will be evaluated over time after TKA using measures of knee range of motion and capsular thickening.

120 patients scheduled to undergo total knee arthroplasty will be recruited from the clinical practice of the Principal Clinical Investigator or his designee at The Steadman Clinic (TSC) and randomized into one of two arms (1:1).

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
120
Inclusion Criteria
  1. Planned primary total knee arthroplasty of a single knee;
  2. Male or female ≥ 18 years of age;
  3. Capacity to personally give informed consent (consent via legally authorized representative will not be accepted) and who are willing to comply with all study-related procedures and assessments.
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Exclusion Criteria
  1. Breastfeeding, pregnant, or planning to become pregnant during participation in the study;
  2. Diagnosed with inflammatory or other arthritis caused by autoimmune disease affecting the study knee;
  3. Previous knee arthroplasty on the study knee;
  4. Previous infection affecting the study knee;
  5. Planned total knee arthroplasty of contralateral knee to occur at any point during the study participation period;
  6. Are hypotensive as confirmed by Principal Clinical Investigator or appropriate designee;
  7. Planned lower extremity surgery (other than TKA in the study leg) for the duration of study participation;
  8. Any condition other than knee osteoarthritis that significantly impairs ability to walk or perform other activities of daily living;
  9. Currently taking: Losartan or other medication in the same drug class; Warfarin or related anticoagulants;
  10. Opioid analgesics taken in the past 8 weeks and are not willing to discontinue these medications through the duration of the study (except as prescribed as standard of care in the immediate post-operative period);
  11. Allergic to any active or inactive ingredient of Losartan;
  12. Taking medication with known adverse Losartan interaction;
  13. Subjects that have any medical condition, including malignancies, laboratory findings, and/or findings in the medical history or in the pre-study assessments that, in the opinion of the Investigator, constitutes a risk or contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation, or prevent the patient from fully participating in all aspects of the study.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Losartan (investigational)LosartanLosartan 12.5 mg, PO, BID, for four weeks post-TKA surgery (on Days 1 through 28, starting the day after surgery).
Placebo (control)Placebo - LosartanLosartan Placebo 12.5 mg, PO, BID, for four weeks post-TKA surgery (on Days 1 through 28, starting the day after surgery).
Primary Outcome Measures
NameTimeMethod
Quantitative Ultrasound Measurement of Capsular Thickness at Lateral RetinaculumBaseline, 6 weeks post-op, and 3 months post-op

Thickness of knee joint capsule will be measured using quantitative ultrasound. The thickness will be measured using the distance between the two bright echoes seen on the ultrasound image that correspond to the superficial and deep edges of the capsule.

Knee Range of MotionBaseline, 6 weeks post-op, and 3 months post-op

Reported as degree of knee Flexion/Extension

Secondary Outcome Measures
NameTimeMethod
Incidence of Treatment-Emergent Adverse EventsFrom date of study drug dosing until the end of the study, an average of 3.5 months

Occurrence of adverse events

Knee Extensor Isometric Strength AssessmentBaseline, and 3 months post-op

Assessed via handheld dynamometer and inclinometer containing a load cell that will digitally record the knee extension force.

TGF-ß multiplex immunoassay assessment of peripheral blood plasma/serumBaseline, 10-17 days post-op, 6 weeks post-op, and 3 months post-op

Biomarkers assessed will include quantifying secreted proteins related to inflammation, fibrosis, and senescence in the non-cellular fraction of the blood (e.g., serum and/or plasma) using commercially available immunocapture assays.

Flow cytometry immunosenescent phenotyping assessment of peripheral blood mononuclear cellsBaseline, 10-17 days post-op, 6 weeks post-op, and 3 months post-op

Cell types measured via flow cytometry and analyzed via immunophenotype and senescent panels.

Patient Reported Outcomes Questionnaire-Numeric Rating Scale for Knee PainBaseline, day of surgery, 10-17 days post-op, 6 weeks post-op, and 3 months post-op

Scale from 1-10. Higher score represents greater knee pain.

Patient Reported Outcomes Questionnaire-Western Ontario and McMaster UniversitiesBaseline, and 3 months post-op

Scale from 0-96. Higher score represents worse knee health.

Patient Reported Outcomes Questionnaire-Veteran's Rand 12-Item Health SurveyBaseline, and 3 months post-op

Includes two subscales to calculate the total score. Higher score represents greater health. Scale standardized to a US Population mean of 50 and standard deviation of 10 points.

Trial Locations

Locations (1)

The Steadman Clinic

🇺🇸

Vail, Colorado, United States

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