Chlorhexidine Gluconate for Neurogenic Bladder

Overseen By Joshua Sterling, MD, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Disqualifiers: Urolithiasis, Vesicoureteral reflux, Renal transplant, 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

70 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to evaluate the feasibility and tolerability of 0.05% Chlorhexidine Gluconate (CGH) bladder instillations in an outpatient setting at the time of suprapubic catheter (SPC) exchange in patients with history of recurrent urinary tract infections (UTI). The main questions are: 1. is instillation of 150mL of CGH for five-minute duration at the time of SPC exchange feasible in an outpatient setting and tolerable for patients. 2. does this protocol decrease the rate of unplanned health care visits and improve patient quality of life. Patients will undergo the treatment protocol during their routine suprapubic catheter exchanges.

Will I have to stop taking my current medications?

If you are currently using other treatments to prevent recurrent urinary tract infections, you will need to stop them while participating in this trial.

Is Chlorhexidine Gluconate safe for use in the bladder?

Chlorhexidine Gluconate can cause severe bladder irritation and allergic reactions in some people, even if they have used it before without problems. It is not recommended for prolonged use in the bladder due to the risk of severe irritation. ^{1 2 3 4 5}

How does the treatment with Chlorhexidine Gluconate for Neurogenic Bladder differ from other treatments?

Chlorhexidine Gluconate is unique because it is used as a bladder instillation, meaning it is directly introduced into the bladder, which is different from many other treatments that might be taken orally or applied externally. However, studies have shown that prolonged contact with the bladder can cause severe irritation, and there is a risk of allergic reactions, making its use potentially problematic compared to other treatments. ^{1 5 6 7 8}

Research Team

Joshua Sterling, MD, MSc

Principal Investigator

Yale University

Eligibility Criteria

This trial is for people who've had a suprapubic catheter for over a year and have had urinary tract infections treated in the last 6 months. It's not for those with certain bladder conditions, kidney issues, or allergies to chlorhexidine. Pregnant or breastfeeding women and patients on other UTI prevention treatments can't join.

Inclusion Criteria

Indwelling suprapubic catheter with insertion date at least 1 year prior to study enrollment date.

I have been treated for a urinary tract infection in the last 6 months.

Exclusion Criteria

I have had a condition where urine flows backward from my bladder to kidneys.

Current radiographic evidence of urolithiasis

I have had a kidney transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Saline Instillation

Participants receive bladder instillations of normal saline for three months during routine SPC exchanges

3 months

Monthly visits for SPC exchange and instillation

Treatment - Chlorhexidine Gluconate Instillation

Participants receive bladder instillations with chlorhexidine gluconate for six months during routine SPC exchanges

6 months

Monthly visits for SPC exchange and instillation

Observation

Participants undergo an observational phase with six months of catheter exchanges without the intervention

6 months

Monthly visits for SPC exchange

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Treatment Details

Interventions

• Bladder instillation with Irrisept

Trial Overview The study tests if rinsing the bladder with Chlorhexidine Gluconate during routine catheter changes is doable in an outpatient setting, tolerable by patients, reduces unplanned healthcare visits, and improves quality of life.

Participant Groups

Group I: Arm I Experimental Treatment 1 Intervention

Participants will get bladder instillations of normal saline for three months and then six months of instillations with chlorohexidine gluconate. After the instillation phase the patients will undergo an observational phase with six months of catheter exchanges without the intervention.

Bladder instillation with Irrisept is already approved in United States, European Union for the following indications:

Approved in United States as Irrisept for:

• Prevention of urinary tract infections in patients with chronic suprapubic catheters

Approved in European Union as Chlorhexidine Gluconate for:

• Antiseptic for skin and wound cleansing
• Preparation for catheterization

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Irrimax Corporation

Industry Sponsor

Trials

11

Recruited

2,100+

Findings from Research

Irrigation of rat bladders with chlorhexidine digluconate solutions (1:5,000 and 1:10,000) for up to 48 hours resulted in severe erosive cystitis in many cases, indicating significant tissue damage.

The study concludes that chlorhexidine should not be used for prolonged bladder irrigation or during intermittent catheterization due to its harmful effects on the bladder mucosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of chlorhexidine irrigation of the bladder in the rat. Harper, WE., Matz, LR.[2019]

In a study involving 22 interstitial cystitis patients, intravesical resiniferatoxin (RTX) was found to be safe at concentrations of 0.05 microM and 0.10 microM, with no serious adverse events reported.

However, the treatment was associated with significant tolerability issues, particularly pain during instillation, which affected 80% of patients in the 0.10 microM group and 87.5% in the 0.05 microM group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective, randomized, double-blind study of safety and tolerability of intravesical resiniferatoxin (RTX) in interstitial cystitis (IC). Chen, TY., Corcos, J., Camel, M., et al.[2018]

In a study of 30 women with interstitial cystitis, intravesical Bacillus Calmette-Guerin (BCG) treatment resulted in a significant improvement in symptoms, with 73% of patients showing over 40% symptom reduction compared to only 20% in the placebo group.

The treatment was found to be safe, with similar adverse events reported in both the BCG and placebo groups, primarily irritative symptoms, and no significant worsening of interstitial cystitis was observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of intravesical Bacillus-Calmette-Guerin in the treatment of female patients with interstitial cystitis: a double-blinded prospective placebo controlled study. Irani, D., Heidari, M., Khezri, AA.[2007]

In a study involving 44 patients with superficial bladder cancer, treatment with interferon (IFN)-alpha 2b showed no local toxicity and was well tolerated, while ethoglucid caused severe chemocystitis in some patients, leading to treatment discontinuation for three individuals.

Efficacy in terms of recurrence rates and time to first recurrence was similar across all treatment groups, indicating that both IFN-alpha 2b and ethoglucid can be effective options, but IFN-alpha 2b may be safer due to the lack of severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective, randomized trial to evaluate high-versus low-dose interferon-alpha 2b versus conventional chemotherapy in prevention of the recurrence of superficial transitional cell carcinoma of the urinary bladder. Hoeltl, W., Hasun, R., Albrecht, W.[2019]

An 84-year-old man experienced anaphylaxis after receiving Instillagel(®) for urethral catheterization, highlighting a serious allergic reaction to chlorhexidine, one of its active ingredients.

This case emphasizes that even patients with prior uneventful exposures to chlorhexidine can develop sensitization, leading to unexpected anaphylactic reactions during subsequent uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anaphylactic reaction to intraurethral chlorhexidine: sensitisation following previous repeated uneventful administration. Dyer, JE., Nafie, S., Mellon, JK., et al.[2021]

A new urinary catheter made from silicone elastomer with chlorhexidine digluconate (CHG) added can effectively release the antibacterial agent over a prolonged period, with higher concentrations (3% and 4%) maintaining release for up to 28 days.

The study found no toxicity associated with the CHG-bearing catheters during in vivo testing, suggesting they are safe for extended use in preventing catheter-associated infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and characterization of an infection inhibiting urinary catheter. Richards, CL., Hoffman, KC., Bernhard, JM., et al.[2014]

Early-life exposure to chlorhexidine gluconate (CHG) in zebrafish resulted in significant defects in oligodendrocyte development and delayed myelination, indicating potential neurodevelopmental toxicity.

The study found structural changes in myelin sheaths and altered locomotor behavior in CHG-exposed zebrafish, highlighting the risks associated with using CHG in neonatal care, especially given its common use despite safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myelin toxicity of chlorhexidine in zebrafish larvae. Choi, EK., Choi, BM., Cho, Y., et al.[2023]

In a study of 141 patients undergoing outpatient flexible cystoscopy, the use of chlorhexidine gluconate in local anesthetic gel did not significantly reduce pain during the procedure compared to a gel without chlorhexidine.

However, patients using the chlorhexidine gel reported significantly higher pain and urgency levels after the procedure, indicating that chlorhexidine may contribute to discomfort following cystoscopy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chlorhexidine in urethral gel: does it cause pain at flexible cystoscopy? Jayathillake, A., Mason, DF., Broome, K., et al.[2013]

References

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

The effect of chlorhexidine irrigation of the bladder in the rat. [2019]

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

Prospective, randomized, double-blind study of safety and tolerability of intravesical resiniferatoxin (RTX) in interstitial cystitis (IC). [2018]

3. Iran pubmed.ncbi.nlm.nih.gov

The efficacy and safety of intravesical Bacillus-Calmette-Guerin in the treatment of female patients with interstitial cystitis: a double-blinded prospective placebo controlled study. [2007]

4. England pubmed.ncbi.nlm.nih.gov

Prospective, randomized trial to evaluate high-versus low-dose interferon-alpha 2b versus conventional chemotherapy in prevention of the recurrence of superficial transitional cell carcinoma of the urinary bladder. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Anaphylactic reaction to intraurethral chlorhexidine: sensitisation following previous repeated uneventful administration. [2021]

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

Development and characterization of an infection inhibiting urinary catheter. [2014]

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

Myelin toxicity of chlorhexidine in zebrafish larvae. [2023]

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

Chlorhexidine in urethral gel: does it cause pain at flexible cystoscopy? [2013]