Clinical trial NCT03038321: Solifenacin, Levofloxacin or Lornoxicam, Which Is Ideal for Management of Intravesical Instillation BCG Side Effects?
Official title: Solifenacin vs Levofloxacin vs Lornoxicam for Management of Intravesical Instillation of Bacillus Calmette-Guerin (BCG) Side Effects A Single Blinded Randomised Controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Non-Muscle-invasive Bladder Cancer (NMIBC)
Bacillus Calmette-Guerin (BCG) Cystitis
Intra-vesical Instillation
Keywords: BCG Cystitis
Bladder Cancer
Levofloxacin
Solifenacin
Lornoxicam
Lead sponsor: Mansoura University
Sponsor class: OTHER
First posted: 2017-01-31
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Comparing the drugs efficacy on decreasing systemic and local side effects of BCG
timeFrame: 6 weeks
Secondary outcomes:
measure: Comparing the drugs effect on decreasing voiding and storage urinary symptoms of BCG
timeFrame: 6 weeks
measure: Prostatic specific antigen (PSA) change
timeFrame: 1 month and 3 months
measure: recurrence free survival
timeFrame: 1 year
Other outcomes:
Locations:
city: Mansoura
country: Egypt
facility: Urology and Nephrology Center
state: Aldakahlia
Study officials:
affiliation: Urology and Nephrology Center
name: Hassan Abol-Enein, MD, Phd
role: STUDY_CHAIR
affiliation: Urology and Nephrology Center
name: Ahmed Mosbah, MD
role: STUDY_DIRECTOR
affiliation: Urology and Nephrology Center
name: Ahmed Elhussein, MBBCH
role: PRINCIPAL_INVESTIGATOR
affiliation: Urology and Nephrology Center
name: Ahmed Elkarta, MBBCH
role: PRINCIPAL_INVESTIGATOR
affiliation: Urology and Nephrology Center
name: Mohamed Soltan
role: PRINCIPAL_INVESTIGATOR
References: