Losartan for Knee Injuries

(LION Trial)

Overseen By Molly Zgoda

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Brigham and Women's Hospital

Disqualifiers: Non-English, Pregnancy, Renal, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 4 weeks

90 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have conditions like severe kidney or liver issues, low blood pressure, or high potassium levels, you may be at increased risk for side effects from losartan.

Is Losartan generally safe for humans?

Losartan has been shown to be generally safe in humans, with studies involving thousands of patients for conditions like high blood pressure and kidney issues. Common side effects include dizziness and headache, but serious side effects are rare. It is well-tolerated even in patients with other health conditions like diabetes and kidney problems. ^{1 2 3 4 5}

How does the drug Losartan differ from other treatments for knee injuries?

Losartan is typically used to treat high blood pressure, but its use in knee injuries is novel as it may help reduce inflammation and improve healing, which is different from traditional surgical or physical therapy approaches. ^{6 7 8 9 10}

What is the purpose of this trial?

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.

Eligibility Criteria

This trial is for individuals who have suffered multi-ligament knee injuries, such as those from sports, accidents, or military training. Participants should be undergoing surgery for these injuries and are looking to improve their recovery outcomes.

Inclusion Criteria

Willingness to comply with the study protocol and assessments

I have had surgery to fix or rebuild at least one ligament.

I have severe injuries in two or more knee ligaments.

Exclusion Criteria

I am not pregnant, planning to become pregnant, or if sexually active, I agree to use contraception during the losartan treatment.

Non-English speaking

Allergic to any active or inactive ingredient of losartan

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preoperative

Preoperative assessments including baseline measurements for outcome measures

1 week

1 visit (in-person)

Treatment

Participants receive either 25 mg/day of losartan or placebo for 30 days post-surgery

4 weeks

1 visit (in-person) at the end of treatment

Follow-up

Participants are monitored for safety and effectiveness, including assessments of knee function and strength

12 months

3 visits (in-person) at 6 months and 12 months, biweekly virtual check-ins starting 6 months post-surgery

Treatment Details

Interventions

• Losartan

Trial Overview The study tests if taking Losartan (25 mg) daily for 30 days after knee surgery can help patients return to work or sport faster, increase range of motion and strength, and reduce inflammation compared to a placebo capsule.

Participant Groups

Group I: Losartan Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Walter Reed National Military Medical Center

Collaborator

Trials

149

Recruited

33,800+

University of Kentucky

Collaborator

Trials

198

Recruited

224,000+

Findings from Research

Losartan, an angiotensin receptor antagonist, effectively reduces blood pressure in patients with essential hypertension, with maximum effects seen at doses around 50 mg, and it is safe for once-daily use based on studies involving over 4,000 patients.

The drug has a favorable safety profile, with no significant adverse effects like elevated serum creatinine or potassium levels, and it causes less cough compared to other antihypertensive medications like hydrochlorothiazide or lisinopril.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Losartan: first of a new class of angiotensin antagonists for the management of hypertension. Carr, AA., Prisant, LM.[2019]

Losartan is an effective antihypertensive medication that works by blocking the type 1 angiotensin II receptor, showing similar efficacy to other common blood pressure medications like enalapril, felodipine, and atenolol in clinical trials involving approximately 3700 patients.

The safety profile of losartan is favorable, with a low incidence of adverse effects similar to placebo, and a lower withdrawal rate due to side effects compared to placebo, although dizziness was reported more frequently by patients taking losartan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of losartan. Goldberg, A., Sweet, C.[2013]

Losartan is a safe and effective antihypertensive medication that blocks the angiotensin II type 1 receptor, showing similar overall adverse event rates compared to placebo in a large study of approximately 3800 patients with various conditions, including diabetes and heart failure.

The most common side effects of losartan were headache and dizziness, with dizziness being the only side effect reported more frequently than in the placebo group, indicating that losartan can be a suitable first-line treatment for hypertension, especially for patients who may not tolerate other medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical safety and tolerability of losartan. Weber, M.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Losartan: first of a new class of angiotensin antagonists for the management of hypertension. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of losartan. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

Clinical safety and tolerability of losartan. [2019]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Losartan in diabetic nephropathy. [2018]

5. Germany pubmed.ncbi.nlm.nih.gov

The effect of losartan on range of motion and rates of manipulation in total knee arthroplasty: a retrospective matched cohort study. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Does lateral release change patellofemoral forces and pressures?: a pilot study. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

Medium-term results of 173 ligamentoplasties of the anterior cruciate ligament using the MacIntosh technique reinforced by the Kennedy ligament augmentation device (LAD). [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

[Knee-ligaments--operation and functional postoperative care (author's transl)]. [2006]

9. United States pubmed.ncbi.nlm.nih.gov

Extensor Mechanism Centralization Using Autograft Hamstring for Laterally Dislocating Patella. [2023]

10. Singapore pubmed.ncbi.nlm.nih.gov

Total knee arthroplasty combined with medial patellofemoral ligament augmentation using a Leeds-Keio ligament for 'Windswept deformity' with ipsilateral valgus deformity and permanent patellar dislocation: A case report and a literature review. [2021]