Losartan for Arthrofibrosis

Overseen By Daniel Waren

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: NYU Langone Health

Must be taking: Losartan

Must not be taking: ACE-inhibitors, Angiotensin blockers

Disqualifiers: Revision surgery, Fracture, Infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if losartan, a medication, can reduce scar tissue and improve movement after knee replacement surgery. Researchers seek to find out if taking losartan before and after surgery enhances knee mobility and reduces the need for additional procedures. The trial includes individuals with osteoarthritis or inflammatory arthritis who are scheduled for knee replacement surgery. Participants must have their primary care doctor confirm that they can safely take losartan. As a Phase 4 trial, losartan is already FDA-approved and proven effective, and this research explores how it can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are already taking an ACE-inhibitor or Angiotensin receptor blocker for hypertension, you cannot participate in this study.

What is the safety track record for Losartan?

Research has shown that losartan is usually well-tolerated, with few side effects. Some studies suggest it might be easier to tolerate than similar drugs. For instance, one study found that children with a rare skin disease experienced only mild side effects when taking losartan. This finding is encouraging for its potential use in treating joint stiffness, known as arthrofibrosis, after knee surgery. The FDA has already approved losartan for treating high blood pressure, which further supports its safety. Overall, the evidence appears promising for using losartan to help reduce joint stiffness after surgery. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Losartan is unique because it targets the underlying inflammation and fibrosis involved in arthrofibrosis, potentially offering a new approach compared to standard treatments like physical therapy, corticosteroids, or surgical interventions. This drug, commonly used for hypertension, may reduce scar tissue formation by modulating the renin-angiotensin system, which is not something traditional treatments focus on. Researchers are excited about losartan because it could provide a less invasive and more effective option for patients suffering from this painful joint condition.

What is the effectiveness track record for Losartan in treating arthrofibrosis?

Research has shown that losartan, which participants in this trial may receive, can help reduce arthrofibrosis—a condition where scar tissue limits joint movement after surgery. Studies found that patients taking losartan were less likely to need manipulation under anesthesia, a procedure that loosens stiff joints, compared to those not taking it. Specifically, patients on losartan were 1.15 times less likely to require this procedure. Losartan blocks a chemical in the body that contributes to excessive tissue growth, potentially improving joint movement after surgery. Overall, these findings suggest that losartan could be a promising treatment for preventing stiffness and aiding recovery in joint surgeries. ^{2 3 5 6 7}

Who Is on the Research Team?

Joshua Rozell, MD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

Inclusion Criteria

Patients have been medically cleared and scheduled for surgery

Patients' primary care physician has verified that the patient can safely take the described dose of Losartan for the duration of the study period.

You have been diagnosed with osteoarthritis or inflammatory arthritis and need a knee replacement surgery.

Exclusion Criteria

Bilateral, simultaneous surgery

You recently had surgery for a broken bone, infection, or cancer.

You are currently taking medication for high blood pressure called ACE-inhibitor or Angiotensin receptor blocker.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative Treatment

Participants receive losartan pre-operatively to evaluate its efficacy on range of motion and incidence of manipulation under anesthesia

2 weeks

Post-operative Treatment

Participants continue to receive losartan post-operatively to assess its impact on range of motion and manipulation under anesthesia

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on range of motion and manipulation under anesthesia

90 days

What Are the Treatments Tested in This Trial?

Interventions

• Losartan

How Is the Trial Designed?

Group I: Losartan Group Experimental Treatment 1 Intervention

Group II: Control Group Active Control 1 Intervention

No additional steps in management are required for the control arm of the study.

Losartan is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Cozaar for:

• Hypertension
• Diabetic nephropathy
• Stroke prevention in hypertension and left ventricular hypertrophy

Approved in European Union as Cozaar for:

• Hypertension
• Diabetic nephropathy
• Heart failure

Approved in Canada as Cozaar for:

• Hypertension
• Diabetic nephropathy
• Heart failure

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Published Research Related to This Trial

Losartan potassium, an angiotensin II receptor antagonist, shows significant haemodynamic benefits in patients with heart failure, based on extensive clinical trials.

The drug is well tolerated with a low incidence of adverse effects related to kidney function, making it a safe option for treating hypertension and heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Losartan in heart failure: preclinical experiences and initial clinical outcomes. Sweet, CS., Rucinska, EJ.[2019]

Losartan/hydrochlorothiazide (HCTZ) is an effective fixed-dose combination therapy for hypertension, providing greater blood pressure reduction than either medication alone, and is particularly beneficial for patients with severe hypertension and left ventricular hypertrophy (LVH).

In the LIFE study, losartan-based therapy demonstrated a lower incidence of cardiovascular events and new-onset diabetes compared to atenolol, highlighting its safety and efficacy in reducing stroke risk and improving overall cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Losartan/Hydrochlorothiazide: a review of its use in the treatment of hypertension and for stroke risk reduction in patients with hypertension and left ventricular hypertrophy. Keating, GM.[2021]

Losartan, a medication for hypertension, was well-tolerated in approximately 2000 patients, showing a lower incidence of adverse effects compared to other antihypertensive drugs, particularly ACE inhibitors.

The most common side effects reported with losartan were headache and dizziness, but overall, it had a better safety profile with only 2.3% of patients withdrawing due to adverse effects, and no significant safety concerns were noted across different demographic groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of losartan compared with atenolol, felodipine and angiotensin converting enzyme inhibitors. Goldberg, AI., Dunlay, MC., Sweet, CS.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39778688/

Losartan May Prevent Clinically Significant Postoperative ... Editorial Commentary: Losartan May Prevent Clinically Significant Postoperative Fibrosis, but Large Database Studies May Not Provide an Answer.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06108063

Mitigation of Arthrofibrosis After Total Knee Arthroplasty ... The purpose of this study is to evaluate the efficacy of Losartan use post-operatively for reducing or preventing the development of arthrofibrosis.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1877056824000598

The association between losartan potassium prescription ... Specifically, losartan TKA patients were 1.18 times less likely to be readmitted within 90 days and 1.15 times less likely to undergo MUA compared to non- ...

4. withpower.com withpower.com/trial/phase-4-2022-a1874

Losartan for Arthrofibrosis · Info for Participants In the LIFE study, losartan-based therapy demonstrated a lower incidence of cardiovascular events and new-onset diabetes compared to atenolol, highlighting its ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12414002/

Patients on Losartan Have Similar Rates of Manipulation ... Patients taking losartan had longer lengths of stay compared to patients not taking losartan (1.34 days vs 1.28 days; p < 0.001). There was no ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11558279/

Angiotensin II receptor blockers and their applications in ... Garg et al. demonstrated that losartan administration led to decreased fibrosis in injured rat muscle while also inhibiting tissue regeneration ...

7. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00479-6/fulltext

Safety and tolerability of losartan to treat recessive ... Our results suggest that losartan was well tolerated by children with RDEB, and provide preliminary evidence that it may reduce disease burden. ...