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

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

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

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Aldakahlia
    • Mansoura, Aldakahlia, Egypt, 35516
      • Urology and nephrology center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mansoura University
• Investigators: Study Director: Ahmed Mosbah, MD, Urology and nephrology center; Principal Investigator: Ahmed Elhussein, MBBCH, Urology and nephrology center; Principal Investigator: Ahmed Elkarta, MBBCH, Urology and nephrology center; Principal Investigator: Mohamed Soltan, Urology and nephrology center

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2017
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: January 15, 2017
• First Submitted That Met QC Criteria: January 28, 2017
• First Posted (Estimate): January 31, 2017

Study Record Updates

• Last Update Posted (Actual): May 23, 2017
• Last Update Submitted That Met QC Criteria: May 19, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Levofloxacin; Bladder Cancer; Solifenacin; BCG Cystitis; Lornoxicam
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Cystitis; Urinary Bladder Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Anti-Infective Agents, Urinary; Renal Agents; Levofloxacin; Lornoxicam
• Other Study ID Numbers: R/17.01.02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: meta-analyses by contact the Prof. Hassan Abol-Enein, MD, Phd (Study Chair)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No