Mitigation of Arthrofibrosis After Total Knee Arthroplasty Using Losartan

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.

Study Overview

• Status: Recruiting
• Conditions: Knee Arthroplasty, Total
• Intervention / Treatment: Drug: Losartan; Drug: Placebo - Losartan

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).

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Suzanne L Page, JD; Phone Number: 970-401-8770; Email: spage@sprivail.org
• Study Contact Backup: Name: Luz Thede; Phone Number: 970-409-7566; Email: lthede@sprivail.org

Study Locations

• United States
  • Colorado
    • Vail, Colorado, United States, 81657
      • Recruiting
      • The Steadman Clinic
      • Contact: Suzanne L Page, JD; Phone Number: 970-401-8770; Email: spage@sprivail.org
      • Principal Investigator: Raymond Kim, MD
      • Contact: Luz Thede; Phone Number: 970-409-7566; Email: lthede@sprivail.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Losartan (investigational); Losartan 12.5 mg, PO, BID, for four weeks post-TKA surgery (on Days 1 through 28, starting the day after surgery).	Drug: Losartan; 12.5 mg oral Losartan taken for 28 days total (4 week postoperative).; Other Names: Losartan potassium
Placebo Comparator: Placebo (control); Losartan Placebo 12.5 mg, PO, BID, for four weeks post-TKA surgery (on Days 1 through 28, starting the day after surgery).	Drug: Placebo - Losartan; Losartan appearance-matched Prosolv EasyTab SP placebo. 12.5 mg oral tablet taken for 28 days total (4 week postoperative).; Other Names: Placebo Oral Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative Ultrasound Measurement of Capsular Thickness at Lateral Retinaculum	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.	Baseline, 6 weeks post-op, and 3 months post-op
Knee Range of Motion	Reported as degree of knee Flexion/Extension	Baseline, 6 weeks post-op, and 3 months post-op

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	Occurrence of adverse events	From date of study drug dosing until the end of the study, an average of 3.5 months
TGF-ß multiplex immunoassay assessment of peripheral blood plasma/serum	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.	Baseline, 10-17 days post-op, 6 weeks post-op, and 3 months post-op
Flow cytometry immunosenescent phenotyping assessment of peripheral blood mononuclear cells	Cell types measured via flow cytometry and analyzed via immunophenotype and senescent panels.	Baseline, 10-17 days post-op, 6 weeks post-op, and 3 months post-op
Knee Extensor Isometric Strength Assessment	Assessed via handheld dynamometer and inclinometer containing a load cell that will digitally record the knee extension force.	Baseline, and 3 months post-op
Patient Reported Outcomes Questionnaire-Numeric Rating Scale for Knee Pain	Scale from 1-10. Higher score represents greater knee pain.	Baseline, day of surgery, 10-17 days post-op, 6 weeks post-op, and 3 months post-op
Patient Reported Outcomes Questionnaire-Western Ontario and McMaster Universities	Scale from 0-96. Higher score represents worse knee health.	Baseline, and 3 months post-op
Patient Reported Outcomes Questionnaire-Veteran's Rand 12-Item Health Survey	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.	Baseline, and 3 months post-op

Collaborators and Investigators

• Sponsor: Steadman Philippon Research Institute
• Investigators: Principal Investigator: Johnny Huard, PhD, Steadman Philippon Research Institute; Principal Investigator: Scott Tashman, PhD, Steadman Philippon Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: October 23, 2023
• First Submitted That Met QC Criteria: October 26, 2023
• First Posted (Actual): October 30, 2023

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: TKA Losartan Arthrofibrosis
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Losartan
• Other Study ID Numbers: 2023-194

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No