Mitigation of Arthrofibrosis After Total Knee Arthroplasty Using Losartan

NCT06108063 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 2023-194
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Knee Arthroplasty, Total

Keywords

TKA Losartan Arthrofibrosis

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• Incidence of Treatment-Emergent 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

  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

  Baseline, 10-17 days post-op, 6 weeks post-op, and 3 months post-op

• Knee Extensor Isometric Strength Assessment

  Baseline, and 3 months post-op

• Patient Reported Outcomes Questionnaire-Numeric Rating Scale for Knee Pain

  Baseline, day of surgery, 10-17 days post-op, 6 weeks post-op, and 3 months post-op

Study Arms (2)

Losartan (investigational)

EXPERIMENTAL

Losartan 12.5 mg, PO, BID, for four weeks post-TKA surgery (on Days 1 through 28, starting the day after surgery).

Drug: Losartan

Placebo (control)

PLACEBO COMPARATOR

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

Interventions

Losartan DRUG

12.5 mg oral Losartan taken for 28 days total (4 week postoperative).

Also known as: Losartan potassium

Losartan (investigational)

Placebo - Losartan DRUG

Losartan appearance-matched Prosolv EasyTab SP placebo. 12.5 mg oral tablet taken for 28 days total (4 week postoperative).

Also known as: Placebo Oral Tablet

Placebo (control)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Planned primary total knee arthroplasty of a single knee;
• Male or female ≥ 18 years of age;
• 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.

You may not qualify if:

• Breastfeeding, pregnant, or planning to become pregnant during participation in the study;
• Diagnosed with inflammatory or other arthritis caused by autoimmune disease affecting the study knee;
• Previous knee arthroplasty on the study knee;
• Previous infection affecting the study knee;
• Planned total knee arthroplasty of contralateral knee to occur at any point during the study participation period;
• Are hypotensive as confirmed by Principal Clinical Investigator or appropriate designee;
• Planned lower extremity surgery (other than TKA in the study leg) for the duration of study participation;
• Any condition other than knee osteoarthritis that significantly impairs ability to walk or perform other activities of daily living;
• Currently taking: Losartan or other medication in the same drug class; Warfarin or related anticoagulants;
• 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);
• Allergic to any active or inactive ingredient of Losartan;
• Taking medication with known adverse Losartan interaction;
• 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.

Sponsors & Collaborators

• Steadman Philippon Research Institute: lead

Study Sites (1)

The Steadman Clinic

Vail, Colorado, 81657, United States

RECRUITING

MeSH Terms

Interventions

Losartan

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Study Officials

• Johnny Huard, PhD

  Steadman Philippon Research Institute

  PRINCIPAL INVESTIGATOR

• Scott Tashman, PhD

  Steadman Philippon Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Suzanne L Page, JD

CONTACT

970-401-8770; spage@sprivail.org

Luz Thede

CONTACT

970-409-7566; lthede@sprivail.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The Investigator or properly trained and delegated study team member (Physician Assistant) will write the prescription for the study medication. The subject's randomization number will be communicated directly to the Vail Health pharmacy. The Vail Health pharmacy will maintain an unblinded, de-identified randomization spreadsheet that documents group allocation for each subject. The Vail Health Pharmacy oversees and manages drug disbursement for research.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: prospective, randomized, double-blind, placebo controlled clinical trial

Study Record Dates

• First Submitted: October 23, 2023
• First Posted: October 30, 2023
• Study Start: March 6, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: March 12, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)