Mitigation of Arthrofibrosis After Total Knee Arthroplasty Using Losartan

Knee Arthroplasty, Total Clinical Trial

Official title:

Mitigation of Arthrofibrosis After Total Knee Arthroplasty Using Losartan

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06108063
• Other study ID #: 2023-194
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 6, 2024
• Est. completion date: June 30, 2027

Study information

• Verified date: March 2024
• Source: Steadman Philippon Research Institute
• Contact: Suzanne L Page, JD
• Phone: 970-401-8770
• Email: spage[@]sprivail.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: June 30, 2027
• Est. primary completion date: June 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Knee Arthroplasty, Total

Intervention

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

Locations

Country	Name	City	State
United States	The Steadman Clinic	Vail	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
Steadman Philippon Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Knee Range of Motion	Reported as degree of knee Flexion/Extension	Baseline, 6 weeks post-op, and 3 months post-op
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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