Losartan for Total Knee Replacement Complications

Overseen By Luz Thede

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Steadman Philippon Research Institute

Must not be taking: Losartan, Anticoagulants, Opioids, others

Disqualifiers: Pregnancy, Autoimmune arthritis, Hypotension, others

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

Compensation: Varies

Number of Visits: 16

Duration: 4 weeks

120 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

If you are currently taking Losartan, similar medications, Warfarin, or related anticoagulants, you will need to stop these before joining the study. Also, if you've taken opioid painkillers in the last 8 weeks, you must be willing to stop them during the study, except right after surgery as needed.

Is Losartan safe for humans?

Losartan, also known as Cozaar or Hyzaar, is generally considered safe for humans and is commonly used to treat high blood pressure and protect the kidneys in people with diabetes. It has been studied extensively for these conditions, and while it may have side effects like dizziness or fatigue, serious adverse effects are rare. ^{1 2 3 4 5}

How does the drug Losartan differ from other treatments for complications after total knee replacement?

Losartan is unique because it is primarily used to treat high blood pressure and heart-related conditions, but its use in total knee replacement complications is novel. Unlike typical treatments for knee surgery complications, Losartan may offer benefits due to its effects on blood vessels and inflammation, which are not the focus of standard orthopedic treatments. ^{5 6 7 8 9}

Research Team

Johnny Huard, PhD

Principal Investigator

Steadman Philippon Research Institute

Scott Tashman, PhD

Principal Investigator

Steadman Philippon Research Institute

Eligibility Criteria

This trial is for adults over 18 who are planning to have a knee replacement surgery on one knee and can consent to the study. They should not be hypotensive, pregnant, or planning pregnancy; nor should they have had previous knee replacements or surgeries planned during the study. They must not take opioids recently or certain medications like Losartan.

Inclusion Criteria

I can make my own medical decisions and agree to follow the study's requirements.

I am scheduled for a total knee replacement on one knee.

Exclusion Criteria

You are allergic to any of the ingredients in Losartan.

My knee arthritis is due to an autoimmune disease.

I am not planning any leg surgery other than knee replacement in the study leg.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Losartan or placebo for four weeks post-TKA surgery

4 weeks

Visits on day of surgery, 10-17 days post-op

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Visits at 6 weeks post-op and 3 months post-op

Treatment Details

Interventions

• Losartan

Trial Overview The trial is testing if taking Losartan before and after knee replacement surgery can prevent arthrofibrosis (stiffness) and improve outcomes. Participants will either receive Losartan or a placebo without knowing which one they're getting.

Participant Groups

Group I: Losartan (investigational) Experimental Treatment 1 Intervention

Losartan 12.5 mg, PO, BID, for four weeks post-TKA surgery (on Days 1 through 28, starting the day after surgery).

Group II: Placebo (control) Placebo Group 1 Intervention

Losartan Placebo 12.5 mg, PO, BID, for four weeks post-TKA surgery (on Days 1 through 28, starting the day after surgery).

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?

Steadman Philippon Research Institute

Lead Sponsor

Trials

11

Recruited

700+

Findings from Research

Outpatient revision knee arthroplasty is safe for carefully selected patients, with 88% of the 102 patients discharged the same day without complications, and no major complications reported within the first 48 hours post-surgery.

The presence of medical comorbidities did not increase the risk of complications, suggesting that with proper patient education and medical optimization, outpatient procedures can be effectively managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Feasibility of Outpatient Revision Total Knee Arthroplasty in Selected Case Scenarios. Law, JI., Adams, JB., Berend, KR., et al.[2022]

In a study of 2033 total knee arthroplasty patients, the annual rate of adverse events decreased from 9.2% in 2002 to 5.8% in 2004, indicating improved safety over time.

Patients with congestive heart failure and chronic obstructive pulmonary disease had a significantly higher risk of adverse events during hospitalization, and experiencing an adverse event was linked to increased length of hospital stay and higher 30-day postprocedure mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events after total knee arthroplasty: a national Medicare study. Huddleston, JI., Maloney, WJ., Wang, Y., et al.[2009]

In a study of 812 patients who underwent total knee replacement, the all-polyethylene tibial components (APT) showed a higher survival rate (97.1%) compared to metal-backed components (MBT) (93.2%), although the difference was not statistically significant.

Younger patients experienced significantly better functional outcomes with APT components compared to MBT, suggesting that all-polyethylene components may be a superior choice for this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes and survival comparison between NexGen all-poly and its metal-backed equivalent in total knee arthroplasty. Apostolopoulos, V., Nachtnebl, L., Mahdal, M., et al.[2023]

In a study of 159 rheumatoid arthritis (RA) patients undergoing total knee arthroplasty (TKA), no increase in postoperative adverse events (AEs) was observed compared to 318 patients with osteoarthritis (OA), despite RA patients having worse preoperative function and higher medication use.

The study found no significant differences in rates of infections or other complications between RA and OA patients, suggesting that with experienced surgeons, TKA can be safely performed in RA patients without increased risk of postoperative AEs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rheumatoid Arthritis Does Not Increase Risk of Short-term Adverse Events after Total Knee Arthroplasty: A Retrospective Case-control Study. LoVerde, ZJ., Mandl, LA., Johnson, BK., et al.[2022]

In a review of 162 patients with 224 total knee replacements, early complications included deep vein thrombosis (3%) and motion limitations requiring manipulation (7%).

Late complications were more prevalent, with patellofemoral arthritis (11%) being the most common and disabling issue, followed by heterotopic bone formation (10%) and loosening (7%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications of total knee replacement. Lovelock, JE., Griffiths, HJ., Silverstein, AM., et al.[2016]

Infection remains the leading cause of failure in revision total knee arthroplasty (TKA), accounting for 51% of cases, but there has been a notable increase in revisions due to mechanical loosening (from 19.1% to 31.9%) and instability (from 11.2% to 13.5%) over the past 17 years.

The study indicates a significant decrease in revisions due to polyethylene wear (from 9.0% to 2.9%) and a relative decrease in infection rates in later revisions, suggesting changing trends in the causes of TKA failures that orthopedic surgeons should be aware of.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trend Shift in the Cause of Revision Total Knee Arthroplasty over 17 Years. Na, BR., Kwak, WK., Lee, NH., et al.[2023]

A case report highlights a potential link between the use of angiotensin-converting enzyme (ACE) inhibitors and the development of acute kidney injury after total knee arthroplasty (TKA), suggesting a need for caution in patients taking these medications during joint replacement surgery.

This relationship, previously studied in cardiac and gastric bypass patients, has not been explored in the context of joint replacement, indicating a gap in current research that could impact patient safety and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute kidney injury in the setting of knee arthroplasty: a case report and discussion investigating Angiotensin-converting enzyme inhibitors as the culprit. Rosenbaum, AJ., Luciano, JA., Marburger, R., et al.[2021]

In a study of 2,974 patients who underwent primary total knee arthroplasty, the overall complication rate was 6.8%, with severe complications occurring in 2.5% of cases.

Key risk factors for severe complications included being male, over 75 years old, having arrhythmia, and having a history of cerebrovascular disease, indicating that these patients may require closer monitoring post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible Risk Factors for Severe Complications Occurring after Primary Total Knee Arthroplasty. Ma, LL., Yu, XR., Weng, XS., et al.[2023]

A systematic review of 40 studies found that the rate of amputation following total knee replacement (TKR) ranges from 0.1% to 10%, highlighting the importance of discussing this risk with patients before surgery.

Deep infection was identified as the leading cause of amputation after TKR, with a notable 5.1% amputation rate in cases of infected TKR, emphasizing the need for careful monitoring and management of infections post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amputation as a Complication after Total Knee Replacement, is it a Real Concern to be Discussed?: A Systematic Review. Mousavian, A., Sabzevari, S., Ghiasi, S., et al.[2021]

References

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

The Feasibility of Outpatient Revision Total Knee Arthroplasty in Selected Case Scenarios. [2022]

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

Adverse events after total knee arthroplasty: a national Medicare study. [2009]

3. Germany pubmed.ncbi.nlm.nih.gov

Clinical outcomes and survival comparison between NexGen all-poly and its metal-backed equivalent in total knee arthroplasty. [2023]

4. Canada pubmed.ncbi.nlm.nih.gov

Rheumatoid Arthritis Does Not Increase Risk of Short-term Adverse Events after Total Knee Arthroplasty: A Retrospective Case-control Study. [2022]

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

Complications of total knee replacement. [2016]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

Trend Shift in the Cause of Revision Total Knee Arthroplasty over 17 Years. [2023]

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

Acute kidney injury in the setting of knee arthroplasty: a case report and discussion investigating Angiotensin-converting enzyme inhibitors as the culprit. [2021]

8. China pubmed.ncbi.nlm.nih.gov

Possible Risk Factors for Severe Complications Occurring after Primary Total Knee Arthroplasty. [2023]

9. Iran pubmed.ncbi.nlm.nih.gov

Amputation as a Complication after Total Knee Replacement, is it a Real Concern to be Discussed?: A Systematic Review. [2021]