Tetrasodium EDTA for Catheter Complications

Overseen By Johane Allard

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Must not be taking: Long-term antimicrobials

Disqualifiers: Alcohol, Drug abuse, Pregnancy, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if tetrasodium EDTA, a catheter lock solution, can reduce blood clots and infections in individuals using a central venous catheter for nutrition. These catheters are essential for patients with chronic intestinal failure who require direct vein nutrition. The trial will compare tetrasodium EDTA with other solutions to identify the best option for maintaining catheter clarity and safety. Individuals who have been stable for at least four weeks and use a catheter for nutrition may qualify.

As an unphased trial, this study provides participants the chance to contribute to significant research that could enhance catheter safety and effectiveness.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on long-term antimicrobial therapy like taurolidine, you cannot participate in the trial.

What prior data suggests that tetrasodium EDTA is safe for catheter use?

Research has shown that tetrasodium EDTA is generally safe for keeping catheters clear. One study found that a 4% tetrasodium EDTA solution reduced problems with central venous catheters (CVCs) by 50% compared to other treatments like heparin, suggesting it might lower risks associated with catheter use.

The solution is clear, colorless, and sterile, containing no preservatives or alcohol, which reduces the chance of allergic reactions. However, individuals allergic to edetate (a component of EDTA) should avoid it. It is also not recommended for pregnant or nursing individuals due to insufficient safety information for these groups.

Overall, evidence indicates that tetrasodium EDTA is well-tolerated, with no major safety concerns reported in the reviewed studies. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Tetrasodium EDTA is unique because it offers a novel approach to preventing catheter complications, especially for patients on home parenteral nutrition. Unlike traditional anticoagulants or antimicrobial locks, tetrasodium EDTA acts by chelating calcium, which can disrupt biofilm formation and reduce the risk of infections and blockages in catheters. Researchers are excited about its potential because it combines both antibacterial and clot-preventing properties in one solution, potentially improving catheter safety and longevity while minimizing the need for antibiotics.

What evidence suggests that tetrasodium EDTA is effective for reducing catheter complications?

Research has shown that tetrasodium EDTA can help reduce catheter-related problems. In Canada, a 4% tetrasodium EDTA solution significantly decreased both catheter blockages and bloodstream infections. One study found a 50% reduction in catheter-related issues compared to older treatments like heparin. This trial will evaluate the effectiveness of tetrasodium EDTA catheter lock solution in home parenteral nutrition patients, aiming to keep catheters clear and reduce the need for replacements. This makes it a promising option for those requiring nutrition through a catheter. ^{1 4 6 7 8}

Who Is on the Research Team?

Ennaliza Salazar

Principal Investigator

TPN team

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are stable on home total parenteral nutrition (HTPN) without acute illnesses. It's not for those allergic to tetrasodium EDTA, unable to consent, with substance abuse issues, pregnant or breastfeeding women, or those with certain severe medical conditions.

Inclusion Criteria

My health has been stable for the last 4 weeks without any new serious illnesses.

I am either male or female.

I am over 18 years old.

Exclusion Criteria

I am on a long-term anti-microbial treatment, not for small intestinal issues.

You have a history of alcohol or drug abuse.

Pregnant and lactating women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tetrasodium EDTA catheter lock solution as part of their home parenteral nutrition regimen

24 months

Monthly assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Tetrasodium EDTA

Trial Overview The study tests a catheter lock solution called Tetrasodium EDTA in patients using HTPN. The goal is to see if it reduces complications like blood clots and infections better than other solutions such as heparin.

How Is the Trial Designed?

Group I: Tetrasodium EDTA cathether lock solution Experimental Treatment 1 Intervention

There is only one arm in this study where home parenteral nutrition patients who meet the inclusion criteria will receive tetrasodium EDTA catheter lock solution.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

In a study of 90 patients undergoing total knee arthroplasty, both tranexamic acid (TXA) and Floseal® significantly reduced blood loss compared to a control group, as indicated by lower decreases in hemoglobin and total drain output.

Floseal® was found to be more effective than TXA in minimizing drain output, suggesting it may be a preferable option for reducing bleeding during surgery without increasing complication rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Floseal® and Tranexamic Acid for Bleeding Control after Total Knee Arthroplasty: a Prospective Randomized Study. Helito, CP., Bonadio, MB., Sobrado, MF., et al.[2022]

In a study involving 60 total knee arthroplasties, QuikClot Combat Gauze (QCG) did not significantly reduce intraoperative bleeding compared to standard gauze, with similar bleeding volumes observed in both groups.

Postoperative blood drainage was slightly higher in the QCG group, and there was no significant difference in blood transfusion rates between the two types of gauze, indicating that QCG may not provide a hemostatic advantage in this surgical context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is Intraoperative Use of QuikClot Combat Gauze Effective for Hemostasis after Total Knee Arthroplasty? Noh, JH., Lee, JW., Nam, YJ., et al.[2018]

Cefuroxime and ceftazidime showed limited microbicidal effects in unpreserved aqueous eye drop formulations, indicating that these antibiotics alone are not sufficient for preserving the formulations against microbial contamination.

Cefuroxime was effectively preserved in the artificial tear formulation Sno Tears, which contains benzalkonium chloride, while ceftazidime was less effectively preserved in the same vehicle but performed better than alternatives like phenylmercuric acetate and chlorhexidine acetate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preservative efficacy in cefuroxime and ceftazidime eye drop formulations. Barnes, AR., Nash, S.[2019]

The development of a topical solution for the corticosteroid tipredane involved a nonirritating cosolvent system that effectively dissolved the drug at a concentration of 0.1% w/w, ensuring safety for skin application.

Formulations using tromethamine as a buffering agent were more stable than those using potassium citrate, as the latter led to precipitation issues, highlighting the importance of selecting appropriate excipients for drug stability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization of cosolvent concentration and excipient composition in a topical corticosteroid solution. Varia, SA., Faustino, MM., Thakur, AB., et al.[2019]

The study found that a 30% concentration of ethanol is compatible with 4% trisodium citrate (TSC) for use as a catheter locking solution, while higher concentrations (35% or more) lead to crystallization.

Although the combination of ethanol and TSC did not alter TSC concentration in glass test tubes, a slight increase in TSC concentration was observed in carbothane hemodialysis catheters, indicating potential interactions that require further investigation before clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ethanol/trisodium citrate for hemodialysis catheter lock. Bell, AL., Gu, X., Burczynski, FJ., et al.[2019]

The study identified Tween 60 and ethylene glycol as the most effective surfactant and cosurfactant, respectively, for enhancing the solubility of ketorolac tromethamine (KT) in ocular nanoemulsions, which is crucial for effective drug delivery.

Most surfactants tested were non-irritant to the conjunctiva, while some cosurfactants showed varying levels of irritation, indicating that careful selection of excipients is important for developing safe ocular formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Studies on Surfactants, Cosurfactants, and Oils for Prospective Use in Formulation of Ketorolac Tromethamine Ophthalmic Nanoemulsions. Smail, SS., Ghareeb, MM., Omer, HK., et al.[2021]

Staphylococcus epidermidis is a major cause of postoperative infections in orthopedic surgeries, leading to the use of antibiotics like cefazolin and cefuroxime for prevention, but increasing methicillin-resistant strains have necessitated the use of glycopeptide antibiotics like vancomycin and teicoplanin.

Regional prophylaxis with teicoplanin during total knee replacement surgery has been shown to be safe and effective, providing higher antibiotic concentrations at the surgical site and achieving similar infection rates compared to traditional systemic prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic prophylaxis in orthopedic prosthetic surgery. de Lalla, F.[2022]

The study found that the formulation of ketorolac tromethamine eye drops with preservatives like benzalkonium chloride and disodium edetate significantly enhanced the drug's permeation through corneas, indicating a potential for improved therapeutic effectiveness.

Increasing the viscosity of the eye drop formulation decreased the drug's permeation, suggesting that optimizing viscosity is crucial for maximizing drug delivery in ocular treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of preservative, antioxidant and viscolizing agents on in vitro transcorneal permeation of ketorolac tromethamine. Malhotra, M., Majumdar, DK.[2014]

Postoperative intravenous tranexamic acid (TXA) significantly reduced total blood loss (TBL) and hidden blood loss (HBL) in patients undergoing total knee arthroplasty (TKA) compared to a placebo, with no significant differences between two dosing regimens of TXA.

The use of TXA did not increase the incidence of venous thromboembolism (VTE) or other complications, indicating it is a safe option for managing blood loss in TKA patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Postoperative Intravenous Tranexamic Acid in Total Knee Arthroplasty: A Prospective Randomized Controlled Study. Xue, CX., Yao, YF., Lv, H., et al.[2021]

Patients who underwent a topical prednisolone acetate trial (PAT) before receiving intravitreal triamcinolone acetonide (IVTA) experienced a significantly lower proportional rise in intraocular pressure (IOP) compared to control patients, indicating a potential protective effect of the PAT.

The PAT group also had a reduced risk of severe IOP spikes and were less likely to require glaucoma surgery, suggesting that prior treatment with prednisolone acetate may enhance safety in patients receiving IVTA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A trial of topical prednisolone acetate before intravitreal triamcinolone acetonide decreases intraocular pressure spikes. Hollands, H., Seif, G., Hollands, S., et al.[2016]

In a study involving 182 patients undergoing total knee arthroplasty, both intra-articular and intravenous administration of tranexamic acid (TXA) were found to be equally effective in controlling blood loss, with no significant difference in hemoglobin reduction post-surgery.

Both methods of TXA administration demonstrated similar safety profiles, as no patients required blood transfusions and there were no significant complications reported, indicating that either route can be safely used in this surgical context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intra-articular versus intravenous tranexamic acid in reducing perioperative blood loss in total knee arthroplasty: a prospective randomized double-blind equivalence trial. Subramanyam, KN., Khanchandani, P., Tulajaprasad, PV., et al.[2022]

In a study of catheters removed from hemodialysis patients, tetrasodium EDTA was found to effectively eradicate biofilm bacteria after a 24-hour treatment, indicating its potential as a catheter lock solution.

The study identified 20 biofilm-positive isolates from catheters, with tetrasodium EDTA showing promise in reducing catheter-related infections, which could benefit patients with limited access to vascular sites.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of in vivo-generated biofilms from hemodialysis catheters to test the efficacy of a novel antimicrobial catheter lock for biofilm eradication in vitro. Kite, P., Eastwood, K., Sugden, S., et al.[2018]

Tetrasodium EDTA, an antimicrobial lock solution, was found to effectively eliminate biofilms formed by various bacteria and fungi on central venous access devices (CVADs), suggesting it could help prevent infections and extend the lifespan of these devices.

This solution offers a promising alternative to traditional antibiotics, potentially reducing the risk of antibiotic resistance while targeting the prevention of hospital-acquired bloodstream infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tetrasodium EDTA Is Effective at Eradicating Biofilms Formed by Clinically Relevant Microorganisms from Patients' Central Venous Catheters. Liu, F., Hansra, S., Crockford, G., et al.[2019]

The 4% tetrasodium EDTA infusion protocol was effective in relieving intraluminal obstruction in 68.8% of the 16 SUB devices treated in 14 cats, indicating its potential as a therapeutic option.

However, more than half of the successful cases (54.5%) experienced a recurrence of obstruction within a median of 87 days, highlighting the need for further research on case selection and treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of tetrasodium EDTA acid for the treatment of intraluminal obstruction of subcutaneous ureteral bypass devices. Duval, V., Dunn, M., Vachon, C.[2022]

Chelators like citrate and EDTA are effective alternatives to heparin in catheter lock solutions, offering benefits such as antimicrobial activity and maintaining catheter patency, which is crucial for patients with cancer or on hemodialysis.

The review highlights the safety and low cost of chelators, making them a promising option for preventing catheter-related bloodstream infections and ensuring the proper functioning of central lines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the prevention and management of central-line-associated bloodstream infections: The role of chelator-based catheter locks. Chaftari, AM., Viola, GM., Rosenblatt, J., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT04559334

NCT04559334 | Compassionate-Use of 4% T-EDTA Lock ... Since its first approval in Canada, the use of 4% T-EDTA lock solution has been associated with a significant decrease in both catheter occlusions and CLABSI ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39576326/

Use of 4% tetrasodium EDTA (KiteLock™) to prevent ... CVC locking with 4% tetrasodium EDTA was associated with sustained reductions in CRBSI and CVC replacement procedure incidence.

3. sterilecareinc.com sterilecareinc.com/wp-content/uploads/2024/08/KiteLock-Evidence-Summary-v5.pdf

KiteLock4%™ Sterile Catheter Lock Solution Use of 4% T-EDTA resulted in a 50% reduction in CVC complications compared to baseline rates on heparin/ELT (incidence rate ratio [IRR] 0.50, 95% CI 0.25-1.004.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04559334

Compassionate-Use of 4% T-EDTA Lock Solution for ... Such obstructions can lead to catheter breakage or embolization of the clot into the bloodstream, which can lead to stroke or death. Other complications related ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11216891/

A retrospective cohort study - PMC - PubMed Central We performed a descriptive cohort study including 14 high-risk pediatric intestinal failure patients receiving 4% T-EDTA as a daily catheter lock solution. CVC ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04559334

NCT04559334 | Compassionate-Use of 4% T-EDTA Lock ... KiteLock™ 4% Sterile Catheter Lock Solution is a single use, clear, colorless and sterile solution. It is free of preservatives, alcohol and latex and is non- ...

7. assets.cdn.thewebconsole.com assets.cdn.thewebconsole.com/S3WEB4798/images/62578f927ed03.pdf?m=381b71b8ae1a202cebfc27362eceb748

SUMMARY OF SAFETY PROFILE KiteLock™ 4% Sterile ... KiteLock™ 4% Sterile Catheter Lock Solution becomes ineffective as an antimicrobial agent in vivo as it immediately binds to circulating calcium ...

8. sterilecareinc.com sterilecareinc.com/wp-content/uploads/2023/10/KiteLock-4-eIFU-1.pdf

KiteLock 4% KiteLock™ 4% Sterile Catheter Lock Solution should not be used in patients with documented hypersensitivity to edetate. Do not use in pregnant and nursing ...