Losartan to Improve Outcomes After Multi-ligament Knee Injury

NCT06933706 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2025P000672
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 3

Brief Summary

Multi-ligament knee injuries (MLKIs) can occur during military training, sports injuries, or traumatic events such as motor vehicle accidents and can be devastating events. These complex injuries involving disruption of 2 or more ligaments often coincide with injuries to arteries, nerves, tendons, menisci, and/or fractures and can be devastating events. MLKIs often require complex treatments nearly 2 in 5 patients suffer complications after surgery. Loss of knee range of motion is the most common complication and is associated with military separation. There are also long-term effects of motion loss, as the need for motion-restoring surgery after MLKI is associated with an increased risk of osteoarthritis within 5 years of surgery. A person's ability to perform both activities of daily living and higher demand physical activities is often impaired both in the short and long term. In fact, only 1 in 3 people return to high-level sport after MLKI. The purpose of this translational randomized clinical trial is to determine if a 30-day course of oral Losartan improves a person's ability to return to work or sport, range of motion and strength, and reduce knee inflammation in the first year after surgical treatment of an MLKI.

Conditions

Multi-ligament Knee Injury

Keywords

knee dislocation; multi-ligament knee injury; losartan

Outcome Measures

Primary Outcomes (1)

• Cincinnati Occupational Rating Scale (CORS)

  The CORS is a valid and reliable 7-item scale that quantifies the hours or number of times a patient performs the following activities: sitting, standing/walking, walking on uneven ground/turning/twisting, climbing, squatting, as well as the frequency of lifting/carrying and the pounds carried. Scores range from 0 to 60 with greater scores being indicative of more strenuous work activities.

  Baseline, 1 month, 6 months, and 12 months

Secondary Outcomes (7)

• Medication Adherence

  1 month

• Time to return to work or sport

  6 months, 1 year

• International Knee Documentation Committee Subjective Knee Form (IKDC)

  Baseline, 1 month, 6 months, and 12 months

• Pain Visual Analogue Scale (VAS)

  Baseline, 1 month, 6 months, and 12 months

• Knee Range of Motion

  Baseline, 1 month, 6 months, and 12 months

Study Arms (2)

Losartan

EXPERIMENTAL

Participants randomized to the Losartan arm will be asked to take 25 mg of losartan per day for 30 days.

Drug: losartan 25 mg

Placebo

PLACEBO COMPARATOR

Participants randomized to the Placebo arm will be asked to take one placebo capsule per day for 30 days.

Other: Placebo capsule

Interventions

losartan 25 mg DRUG

Losartan is an angiotensin-II inhibitor that modulates the renin-angiotensin system by blocking the activation of angiotensin type 1 receptors, thus preventing binding with angiotensin-II and decreasing blood pressure. Losartan has a broader therapeutic potential for muscle healing and treatment for diseases ranging from rheumatoid arthritis, osteoarthritis, chronic kidney disease, Marfan syndrome, and fatty liver. TGF-β plays an active role in fibrosis leading to the formation of adhesions and scar tissue. By limiting the formation of adhesions and scar tissue, losartan may reduce pain, myofibroblast activity, synovitis, fibrosis, and cartilage degeneration.

Losartan

Placebo capsule OTHER

The placebo capsule will look identical to the active study drug, but will not have any active ingredient and will be filled with corn starch

Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Multi-ligament knee injury defined as a complete grade III injury of 2 or more ligaments
• At least one ligament surgically reconstructed or repaired
• Willingness to comply with the study protocol and assessments

You may not qualify if:

• Allergic to any active or inactive ingredient of losartan
• Pregnant, planning to become pregnant, or sexually active females choosing not to use effective means of contraception during the 30-day course of losartan
• Those at increased risk of losartan related side effects including those with severe renal insufficiency, hepatic disease, hypotension, and/or hyperkalemia
• Have a history of prior knee ligament surgery of the involved knee
• Undergoing staged surgical procedures in the treatment of MLKI
• Have a traumatic brain injury that limits their ability to participate in their postoperative care or any condition that would preclude the ability to comply with postoperative rehabilitation
• Have a concomitant injury or underwent a surgical procedure that will preclude the ability to perform range of motion exercises (i.e. surgery for extensor mechanism rupture or avulsion, vascular graft surgery)

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• University of Kentucky: collaborator
• Walter Reed National Military Medical Center: collaborator

Study Sites (3)

University of Kentucky

Lexington, Kentucky, 40536, United States

NOT YET RECRUITING

Walter Reed National Military Medical Center

Bethesda, Maryland, 20814, United States

NOT YET RECRUITING

Mass General Brigham

Foxborough, Massachusetts, 02035, United States

RECRUITING

MeSH Terms

Conditions

Knee Dislocation

Interventions

Losartan

Condition Hierarchy (Ancestors)

Joint Dislocations; Joint Diseases; Musculoskeletal Diseases; Wounds and Injuries; Knee Injuries; Leg Injuries

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

• Cale Jacobs, PhD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cale Jacobs, PhD

CONTACT

508-216-1145; cjacobs@bwh.harvard.edu

Molly Zgoda

CONTACT

508-216-1145; mzgoda@mgb.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 11, 2025
• First Posted: April 18, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): September 30, 2029
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Time Frame: IPD will be made available after data analysis has been completed and the primary study manuscript has been accepted for publication (anticipated March 2030), and will remain available for a minimum of 7 years (anticipated March 2037).
• Access Criteria: The project team will make their data available as widely and as freely as possible while safeguarding the privacy of participants and protecting confidential and proprietary data. Furthermore, any research resources will be shared in line with the policies adopted by DOD for the purposes of this grant. Data will be made publicly available, and requestors will be required to complete a data-sharing agreement with Brigham and Women's Hospital. The purpose of the data-sharing agreement is to ensure data security at the recipient site and clarify that manipulating the data for the purposes of identifying subjects is strictly prohibited. No limits or caveats for co-authorship will be required as a precondition for receiving data.

Locations

US (3)