A Randomized Prospective Trial Comparing Bacillus Calmette-Guerin (BCG) RIVM and Russian Strains in Non-Muscle Invasive Bladder Cancer: Efficacy and Side Effects
Phase: PHASE4
Conditions: Non Muscle Invasive Bladder Cancer
Sponsor: Ankara University

Official Title: A Randomized Prospective Trial Comparing Bacillus Calmette-Guerin 
(BCG) RIVM and Russian Strains in Non-Muscle Invasive Bladder Cancer: Efficacy 
and Side Effects 
NCT Number: [Not Yet Assigned] 
Date of Document: 05.01.2025 
 
Study Protocol and Statistical Analysis Plan 
Principal Investigator: Dr. Khaled Obaid, Urologist 
Background and Rationale 
Bladder cancer remains a significant health burden globally, with non-muscle invasive 
bladder cancer (NMIBC) representing a majority of cases. Intravesical Bacillus 
Calmette-Guerin (BCG) therapy is widely accepted as a standard adjuvant treatment 
for intermediate- and high-risk NMIBC. However, the comparative efficacy and safety 
profiles of different BCG substrains remain unclear. This study aims to address this 
gap by comparing the RIVM and Russian BCG substrains. 
Objectives 
 
Primary Objective: To evaluate the efficacy of BCG RIVM versus BCG 
Russian substrains in terms of recurrence-free survival (RFS) and 
progression-free survival (PFS). 
 
Secondary Objective: To compare the safety and adverse event profiles 
between the two substrains. 
Study Design 
This is a randomized prospective clinical trial conducted at Ankara University Ibni 
Sina Hospital from January 2019 to December 2022. 
Inclusion Criteria 
1. Age ≥18 years. 
2. Histopathologically confirmed NMIBC (Ta, T1, or CIS). 
3. Intermediate-, high-, or very high-risk classification based on EAU guidelines. 
4. No prior BCG therapy within the last year. 
5. No evidence of upper urinary tract carcinoma or distant metastases. 
6. Minimum follow-up period of 12 months. 
Exclusion Criteria 

1. Inadequate BCG therapy (fewer than 5 induction doses or fewer than 2 
maintenance doses). 
2. Follow-up period less than 12 months. 
3. Use of multiple BCG strains. 
4. Previous history of BCG therapy. 
Methods 
Randomization 
Patients were randomly assigned to receive either BCG RIVM (n=61) or BCG 
Russian (n=64). 
Intervention 
Both groups received an induction course of six weekly intravesical BCG instillations, 
followed by maintenance therapy as per risk stratification protocols. 
Outcome Measures 
 
Primary Outcomes: 
o Recurrence-free survival (RFS): Time from randomization to tumor 
recurrence. 
o Progression-free survival (PFS): Time from randomization to disease 
progression. 
 
Secondary Outcomes: 
o Adverse events: Assessed using the National Cancer Institute Common 
Terminology Criteria for Adverse Events (CTCAE). 
Statistical Analysis 
 
Kaplan-Meier survival analysis for RFS and PFS. 
 
Chi-square tests for categorical variables. 
 
Cox proportional hazards model for multivariate analysis. 
 
P-value <0.05 considered statistically significant. 
Results Summary 
 
A total of 125 patients were analyzed: 61 in the BCG RIVM group and 64 in 
the BCG Russian group. 
 
No significant difference in RFS or PFS between the groups. 
 
Adverse event rates were comparable. 

Conclusion 
This trial demonstrates that BCG RIVM and Russian substrains offer similar efficacy 
and safety for the treatment of NMIBC. These findings provide flexibility in substrain 
selection based on availability and institutional preference.