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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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
|
| 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Losartan | Drug | 12.5 mg oral Losartan taken for 28 days total (4 week postoperative). |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Suzanne L Page, JD | Contact | 970-401-8770 | spage@sprivail.org | |
| Luz Thede | Contact | 970-409-7566 | lthede@sprivail.org |
| Name | Affiliation | Role |
|---|---|---|
| Johnny Huard, PhD | Steadman Philippon Research Institute | Principal Investigator |
| Scott Tashman, PhD | Steadman Philippon Research Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Steadman Clinic | Recruiting | Vail | Colorado | 81657 | United States |
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| ID | Term |
|---|---|
| D019808 | Losartan |
| ID | Term |
|---|---|
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
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prospective, randomized, double-blind, placebo controlled clinical trial
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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.
| Placebo - Losartan | Drug | Losartan appearance-matched Prosolv EasyTab SP placebo. 12.5 mg oral tablet taken for 28 days total (4 week postoperative). |
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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 |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013777 | Tetrazoles |