Multi-ligament Knee InjuryPhase 2LIONNCT06933706
Losartan to Improve Outcomes After Multi-ligament Knee Injury
A Phase 2 study testing losartan 25 mg in people with Multi-ligament Knee Injury, run by Brigham and Women's Hospital at 3 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 40 years
- Conditions the study is for
- Multi-ligament Knee Injury
- What is being tested?
- losartan 25 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 3 sitesUnited States
- Study dates
- 1 Oct 2025to 30 Sep 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 3 recruiting
- Not yet recruiting
Walter Reed National Military Medical Center
Bethesda, Maryland, 20814
Xiaoning Yuan, MD, PhD
- Recruiting
Mass General Brigham
Foxborough, Massachusetts, 02035
Cale Jacobs, 508-216-1145, cjacobs@bwh.harvard.edu
- Not yet recruiting
University of Kentucky
Lexington, Kentucky, 40536
Austin Stone, MD, PhD
About this study
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.
Read the detailed description
Whether the result of military training, a sports injury, or trauma, multi-ligament knee injuries (MLKIs) can be devastating events. MLKI treatment is complex and 38% of all patients report postoperative complications. Loss of knee range of motion (ROM) is the most common complication and is significantly associated with military separation. There are long-term effects of ROM loss, as the need for motion-restoring surgery after MLKI was a significant predictor of physician-diagnosed osteoarthritis within 5 years of surgery. An individual's ability to perform both activities of daily living and higher demand physical activities is thus frequently impaired both in the short and long term. Losartan, an angiotensin receptor blocker, is an FDA-approved treatment for hypertension but because of its multiple mechanisms of action, this low-cost and widely available medication could be repurposed to improve outcomes after MLKI.
Objectives: The purpose of this study is to determine if a 30-day course of oral losartan will improve a person's ability to return to duty or sport within 12 months post-surgery, improve range of motion and strength, and reduce synovitis and capsular thickening after MLKI.
Specific Aims and Study Design: The LION Trial is a double-blind Randomized Controlled Trial to compare the losartan versus placebo with the primary outcome variable being Cincinnati Occupational Rating Scale scores 12 months after surgery. Ninety patients enrolled and will be randomized to take either 25 mg/day of losartan or oral placebo for the first 30 days after surgery. Assessments will include patient-reported outcomes, time to return to duty/sport, knee ROM, isokinetic strength testing, and quantitative ultrasound assessments of synovitis and capsular thickening. Data will be collected at 4 time points: preoperative, after completing the 30-day course of study medication, and 6 months and 12 months after surgery. The investigators will test the following specific aims:
Aim 1: Determine if a 30-day postoperative course of losartan improves the ability to return to duty or sports and patient-reported outcomes when compared to placebo following MLKI.
Aim 2: Assess whether losartan results in more symmetric knee range of motion and quadriceps strength following MLKI when compared to placebo.
Aim 3: Compare ultrasound measures of capsular thickening and synovitis between groups treated with losartan versus placebo following surgical treatment of MLKI.
- Conditions
- Multi-ligament Knee Injury
- Being tested
- losartan 25 mg, Placebo capsule
- Keywords
- knee dislocation, multi-ligament knee injury, losartan
- Medical subject headings
- Knee Dislocation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
losartan 25 mgDrug
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.
Placebo capsuleOther
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
| Study group | Role | What they receive |
|---|---|---|
| Losartan | Experimental | Participants randomized to the Losartan arm will be asked to take 25 mg of losartan per day for 30 days. Receives: 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. Receives: Other: Placebo capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, 1 month, 6 months, and 12 months
Secondary outcomes (7)
Medication Adherence
By counting the number of pills remaining in the participant's medication bottle, we will determine the percentage of the study drug that was taken.
Measured: 1 month
Time to return to work or sport
Beginning 6 months after surgery, participants will be contacted biweekly via their self-selected method (phone, text, or email) to determine the date that they returned to their pre-injury level or work and/or sport.
Measured: 6 months, 1 year
International Knee Documentation Committee Subjective Knee Form (IKDC)
The IKDC is an 18 item instrument has been shown to be valid, reliable, and responsive, and has been previously used to assess outcomes following MLKI procedures. Scores range from 0 to 100 with 100 higher scores indicative of less pain and better knee function.
Measured: Baseline, 1 month, 6 months, and 12 months
Pain Visual Analogue Scale (VAS)
Participants will be asked to rate their pain on a 10 cm scale in 3 different scenarios: worst pain in the past 24 hours, best pain in the past 24 hours, and average pain in the past 24 hours
Measured: Baseline, 1 month, 6 months, and 12 months
Knee Range of Motion
Bilateral knee flexion and extension range of motion will measured using a long-arm goniometer.
Measured: Baseline, 1 month, 6 months, and 12 months
Quadriceps Strength
Quadriceps strength will be assessed bilaterally using an isokinetic dynamometer 6 and 12 months after surgery. Peak torque of the operative limb will be expressed as a percentage of the peak torque of the non-operative limb, which is termed the limb symmetry index.
Measured: 6 months, 1 year
Synovitis Grade
Dynamic ultrasound will be used to assess the grade of synovitis. Superb microvascular imaging (SMI) will be used to assess synovitis. SMI is similar to Power Doppler; however, visualizes smaller, slower velocity vessels, and as such, SMI has been found to be more sensitive in the assessment of knee synovitis. Participants will be positioned supine with knees in 30° of flexion. Longitudinal suprapatellar scans will be acquired in 3 standardized regions defined by the midline, lateral, and medial patellar poles. Synovitis will be visually graded by a trained radiologist as none, mild, moderate, or severe based on the percentage of the area of interest with visible SMI signal.
Measured: 1 month, 6 months, and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2025
- Study start1 Oct 2025
- Primary completion30 Sep 2029 (estimated)
- Study completion30 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multi-ligament Knee InjuryStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Kentucky, Walter Reed National Military Medical Center
- Responsible party
- Principal investigator, Cale Andrew Jacobs, PhD, Brigham and Women's Hospital
- Investigators
- Cale Jacobs, PhD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06933706
- Sponsor's protocol ID
- 2025P000672
- Acronym
- LION
- Status last verified
- Jan 2026
- First submitted
- 11 Apr 2025
- Last updated
- 20 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD from this project will be made available to the research community and to the public at large. Data will be shared through the Harvard Dataverse data repository. A rich dataset will be created which will include patient demographic information, patient-reported outcomes, isokinetic strength, range of motion, and ultrasound assessments of knee synovitis. Demographic information will include patient age, sex, race, ethnicity, body mass index, injury history, intraoperative findings, and surgical treatment. Patient-reported outcomes will include the Cincinnati Occupational Rating Scale (CORS) scores, International Knee Documentation Committee (IKDC) scores, and VAS pain scores
Publications
Kehoe S, Stone A, Yuan X, Conley C, Hawk G, Smith S, Zgoda M, Corey N, Johnson D, Wilson B, Zhou L, Berkson E, Goertz S, Huff L, Hutchinson I, Matzkin E, Richardson L, Lattermann C, Jacobs C. Losartan to Improve Outcomes after multi-ligament kNee injury (LION Trial). Trials. 2026 Apr 14;27(1):388. doi: 10.1186/s13063-026-09714-3.
PubMed 41981668
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Losartan to Improve Outcomes After Multi-ligament Knee Injury
- ClinicalTrials.gov ID
- NCT06933706
- Acronym / sponsor ID
- LION / 2025P000672
- Conditions
- Multi-ligament Knee Injury
- Keywords
- knee dislocation, multi-ligament knee injury, losartan
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- University of Kentucky, Walter Reed National Military Medical Center
- Study start
- 1 Oct 2025 (actual)
- Primary completion
- 30 Sep 2029 (estimated)
- Study completion
- 30 Sep 2029 (estimated)
- First posted
- 18 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Whether the result of military training, a sports injury, or trauma, multi-ligament knee injuries (MLKIs) can be devastating events. MLKI treatment is complex and 38% of all patients report postoperative complications. Loss of knee range of motion (ROM) is the most common complication and is significantly associated with military separation. There are long-term effects of ROM loss, as the need for motion-restoring surgery after MLKI was a significant predictor of physician-diagnosed osteoarthritis within 5 years of surgery. An individual's ability to perform both activities of daily living and higher demand physical activities is thus frequently impaired both in the short and long term. Losartan, an angiotensin receptor blocker, is an FDA-approved treatment for hypertension but because of its multiple mechanisms of action, this low-cost and widely available medication could be repurposed to improve outcomes after MLKI.
Objectives: The purpose of this study is to determine if a 30-day course of oral losartan will improve a person's ability to return to duty or sport within 12 months post-surgery, improve range of motion and strength, and reduce synovitis and capsular thickening after MLKI.
Specific Aims and Study Design: The LION Trial is a double-blind Randomized Controlled Trial to compare the losartan versus placebo with the primary outcome variable being Cincinnati Occupational Rating Scale scores 12 months after surgery. Ninety patients enrolled and will be randomized to take either 25 mg/day of losartan or oral placebo for the first 30 days after surgery. Assessments will include patient-reported outcomes, time to return to duty/sport, knee ROM, isokinetic strength testing, and quantitative ultrasound assessments of synovitis and capsular thickening. Data will be collected at 4 time points: preoperative, after completing the 30-day course of study medication, and 6 months and 12 months after surgery. The investigators will test the following specific aims:
Aim 1: Determine if a 30-day postoperative course of losartan improves the ability to return to duty or sports and patient-reported outcomes when compared to placebo following MLKI.
Aim 2: Assess whether losartan results in more symmetric knee range of motion and quadriceps strength following MLKI when compared to placebo.
Aim 3: Compare ultrasound measures of capsular thickening and synovitis between groups treated with losartan versus placebo following surgical treatment of MLKI.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Losartan | Experimental | Drug: losartan 25 mgParticipants randomized to the Losartan arm will be asked to take 25 mg of losartan per day for 30 days. |
| Placebo | Placebo comparator | Other: Placebo capsuleParticipants randomized to the Placebo arm will be asked to take one placebo capsule per day for 30 days. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| losartan 25 mgLosartan 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. | Drug | Losartan |
| Placebo capsuleThe placebo capsule will look identical to the active study drug, but will not have any active ingredient and will be filled with corn starch | Other | Placebo |
Primary outcome
Cincinnati Occupational Rating Scale (CORS)
Time frame: Baseline, 1 month, 6 months, and 12 months
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.
7 secondary outcomes
Medication Adherence
Time frame: 1 month
Time to return to work or sport
Time frame: 6 months, 1 year
International Knee Documentation Committee Subjective Knee Form (IKDC)
Time frame: Baseline, 1 month, 6 months, and 12 months
Pain Visual Analogue Scale (VAS)
Time frame: Baseline, 1 month, 6 months, and 12 months
Knee Range of Motion
Time frame: Baseline, 1 month, 6 months, and 12 months
Quadriceps Strength
Time frame: 6 months, 1 year
Synovitis Grade
Time frame: 1 month, 6 months, and 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2026.
- Derived from this study: PubMed 41981668Kehoe S, Stone A, Yuan X, Conley C, Hawk G, Smith S, Zgoda M, Corey N, Johnson D, Wilson B, Zhou L, Berkson E, Goertz S, Huff L, Hutchinson I, Matzkin E, Richardson L, Lattermann C, Jacobs C. Losartan to Improve Outcomes after multi-ligament kNee injury (LION Trial). Trials. 2026 Apr 14;27(1):388. doi: 10.1186/s13063-026-09714-3.
- Individual participant dataSharing planned: Yes. IPD from this project will be made available to the research community and to the public at large. Data will be shared through the Harvard Dataverse data repository. A rich dataset will be created which will include patient demographic information, patient-reported outcomes, isokinetic strength, range of motion, and ultrasound assessments of knee synovitis. Demographic information will include patient age, sex, race, ethnicity, body mass index, injury history, intraoperative findings, and surgical treatment. Patient-reported outcomes will include the Cincinnati Occupational Rating Scale (CORS) scores, International Knee Documentation Committee (IKDC) scores, and VAS pain scores
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Cale Jacobs, PhD principal investigator
Brigham and Women's Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing losartan 25 mg in people with Multi-ligament Knee Injury, run by Brigham and Women's Hospital at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Cale Jacobs, PhD (508-216-1145, cjacobs@bwh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cincinnati Occupational Rating Scale (CORS) (time frame: Baseline, 1 month, 6 months, and 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06933706, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2026.