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

Phase 4

• Conditions: Non-Muscle-invasive Bladder Cancer (NMIBC); Bacillus Calmette-Guerin (BCG) Cystitis; Intra-vesical Instillation
• Interventions: Drug: sofenacin; Drug: Tavanic; Drug: Xefo

• Registration Number: NCT03038321
• Lead Sponsor: Mansoura University

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2017-01-15
• Study First Submitted QC: 2017-01-28
• Study First Posted: 2017-01-31
• Study Start: 2017-02-01
• Status Verified: 2017-03
• Last Update Submitted: 2017-05-19
• Last Update Posted: 2017-05-23
• Primary Completion: 2017-12
• Study Completion: 2019-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 150

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
solifenacin	sofenacin	(Sofenacin ''solifenacin 10 m'') \[Marcyrl Pharmaceutical Industries - Egypt\]
levofloxacin	Tavanic	(Tavanic ''levofloxacin 500 mg'') \[Sanofi-Aventis - Egypt\]
lornoxicam	Xefo	(Xefo ''lornoxicam 8 mg'') \[Multi-Apex - Egypt, under license of: NYCOMED, Austria\]

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Urology and Nephrology Center; 🇪🇬 Mansoura, Aldakahlia, Egypt