Solifenacin, Levofloxacin or Lornoxicam, Which Is Ideal for Management of Intravesical Instillation BCG Side Effects?

Study Overview
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Brief Summary
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Compare the different supposed clinical treatment of side effects associated with intravesical BCG by levofloxacin (quinolones) vs solifenacin (selective anti-muscarinic) vs lornoxicam (NSAID)

Detailed Description
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For urothelial carcinoma (UC), which accounts for over 90% of bladder cancers, more than 70% of bladder cancer patients present with non-muscle-invasive disease. Approximately 40-80% of these tumors will recur within the first year, of which 10-25% will progress to muscle-invasive disease. Intravesical treatments with cytotoxic chemotherapy and immunotherapy have become the mainstay following transurethral resection (TUR). Increasing knowledge of BCG use allows for effective management of these once debilitating side effects. The majority of patients will still experience cystitis-like symptoms to some degree, including urinary frequency (71%), cystitis (67%), fever (25%), and hematuria (23%). Oxybutynin increases in fever, flu-like symptoms, dry mouth and constipation. However, in this study oxybutynin started the night before treatment causing an element of incomplete bladder emptying and allowing an increased BCG dwell time. We think that these effect can be reversed by use anticholinergic 6 hours post BCG instillation Anti-inflammatory drugs significantly reduced BCG-induced granulocyte activation and did not impair BCG-induced lymphocyte cytotoxicity against bladder tumor cells in mice. The committee of International Bladder Cancer Group (IBCG) recommend use of anti-inflammatory agents (NSAIDs) for treatment of non-bacterial or chemical cystitis and other systemic BCG side effect. Fluoroquinolone with tuberculostatic properties, has been shown to significantly prolong survival in mice with BCG systemic infection and did not affect the antitumor efficacy of BCG. ofloxacin significantly decreased by 18.5% the incidence of class II or higher moderate and severe adverse events of BCG. Because of sparse published studies on BCG side effect management, the 2016 European Association of Urology (EAU) guidelines management options for side effects associated with intravesical BCG modify the IBCG committee clinical practice without any degree of recommendation. So, in this study the investigators will try to fill the gap in the literature.

Official Title
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Solifenacin vs Levofloxacin vs Lornoxicam for Management of Intravesical Instillation of Bacillus Calmette-Guerin (BCG) Side Effects A Single Blinded Randomised Controlled Study

Conditions
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Non-Muscle-invasive Bladder Cancer (NMIBC), Bacillus Calmette-Guerin (BCG) Cystitis, Intra-vesical Instillation

Intervention / Treatment
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* Drug: sofenacin
* Drug: Tavanic
* Drug: Xefo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Patients classified as intermediate or high risk of the bladder tumour Exclusion Criteria: Patient over 80 years (natural decline in immune system function) Refuse to complete study requirements Contraindication to BCG therapy High post-void residual (PVR) above 85 ml American Urological Association (AUA) Symptoms score above 20 Sensitivity to previously mentioned 3 drugs High serum creatinine

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: solifenacin<br>(Sofenacin ''solifenacin 10 m'') [Marcyrl Pharmaceutical Industries - Egypt] | Drug: sofenacin<br>* solifenacin 10 mg, 6 hours after IVI of BCG and continue for another 2 days post instillation<br>* Other names: Solfenacin 10 mg;|
| Active Comparator: levofloxacin<br>(Tavanic ''levofloxacin 500 mg'') [Sanofi-Aventis - Egypt] | Drug: Tavanic<br>* levofloxacin 500 mg, 6 hours after IVI of BCG and continue for another 2 days post instillation.<br>* Other names: levofloxacin 500;|
| Active Comparator: lornoxicam<br>(Xefo ''lornoxicam 8 mg'') [Multi-Apex - Egypt, under license of: NYCOMED, Austria] | Drug: Xefo<br>* lornoxicam 8 mg, 6 hours after IVI of BCG and continue for another 2 days post instillation.<br>* Other names: lornoxicam;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparing the drugs efficacy on decreasing systemic and local side effects of BCG | __ Outcome Measure by Four-class classification grid of BCG adverse events | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparing the drugs effect on decreasing voiding and storage urinary symptoms of BCG | __ Outcome Measure by overactive bladder symptoms scores and American Urological Association Symptom Index | 6 weeks | 
| Prostatic specific antigen (PSA) change | __ Outcome Measure by PSA measure 1 and 3 months post instillation | 1 month and 3 months | 
| recurrence free survival | __ Outcome Measure by Number of patients surviving for one year without tumor recurrence will be counted and compared | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BCG Cystitis, Bladder Cancer, Levofloxacin, Solifenacin, Lornoxicam