BCG-Induced Cystitis, Urinary Bladder Neoplasms
Conditions
Keywords
Hyaluronic Acid, BCG-induced Cystitis, BCG-related Bladder Pain, Non-Muscle Invasive Bladder Cancer (NMIBC), Interstitial Cystitis
Brief summary
Intravesical Bacillus Calmette-Guérin (BCG) therapy is the standard adjuvant treatment for patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC). However, BCG therapy frequently induces local bladder irritation symptoms including urinary frequency, urgency, dysuria, hematuria, and suprapubic pain, which may reduce quality of life and lead to treatment interruption. Blad-Care™ is an intravesical therapy containing hyaluronic acid and chondroitin sulfate, key components of the urothelial glycosaminoglycan (GAG) layer. Restoration of the GAG layer may protect the bladder mucosa and reduce inflammation-induced bladder irritation symptoms. This prospective randomized study aims to determine whether early administration of intravesical Blad-Care during BCG induction improves BCG-induced bladder toxicity compared with delayed administration after completion of BCG induction therapy.
Detailed description
Non-muscle-invasive bladder cancer (NMIBC) accounts for approximately 70-75% of newly diagnosed bladder cancers. Intravesical BCG therapy after transurethral resection of bladder tumor (TURBT) significantly reduces tumor recurrence and progression in intermediate- and high-risk NMIBC. Despite its proven oncologic benefit, BCG therapy commonly induces local bladder inflammation resulting in urinary frequency, urgency, dysuria, hematuria, and suprapubic pain. These adverse effects may impair patient quality of life and reduce adherence to BCG therapy. Experimental evidence suggests that BCG-induced cystitis is associated with damage to the urothelial glycosaminoglycan (GAG) layer, which normally protects the bladder mucosa from urinary irritants. Disruption of this protective barrier may contribute to bladder irritation symptoms. Blad-Care™ contains hyaluronic acid and chondroitin sulfate, two major components of the GAG layer, and may restore the urothelial protective barrier and reduce bladder inflammation. Previous studies have suggested that GAG restoration therapy may improve symptoms in patients with chemical cystitis; however, evidence regarding its role during BCG therapy remains limited, and the optimal timing of administration has not been established. This multicenter prospective randomized study will compare early versus delayed intravesical administration of Blad-Care during BCG induction in patients with NMIBC to determine the optimal timing for reducing BCG-induced bladder toxicity.
Interventions
DRUGHyaluronic Acid and Chondroitin Sulfate (Blad-Care™)
Intravesical instillation of a sterile solution containing sodium hyaluronate and chondroitin sulfate designed to restore the urothelial glycosaminoglycan (GAG) layer.
Sponsors
BLAD-HYA Group
Eulji University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Masking description
This is an open-label study where both investigators and participants are aware of the assigned administration schedule due to the nature of the sequential vs. concurrent treatment timing.
Intervention model description
This is a multicenter, prospective, randomized, open-label study to determine the optimal intravesical instillation schedule of Blad-Care™ for alleviating BCG-induced local side effects in patients with non-muscle invasive bladder cancer (NMIBC). Participants are randomized 1:1 into two parallel groups: Group A (Early Blad-Care Administration): Participants receive 6 weekly BCG instillations. For the final 3 weeks (Weeks 4-6), Blad-Care™ is administered immediately after each BCG dose. Group B (Delayed Blad-Care Administration): Participants receive 6 weekly BCG instillations alone. Following the BCG course, Blad-Care™ is administered once a week for 3 consecutive weeks (Weeks 7-9). The primary goal is to compare the symptom relief efficacy of these two schedules using the sum of ICSI and ICPI scores. Assessments are conducted at four time points: baseline, after the 3rd BCG, after the 6th BCG, and 2 months post-BCG therapy.
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults aged ≥19 years * Histologically confirmed non-muscle-invasive bladder cancer * Candidates for intravesical BCG therapy * Negative urine culture prior to BCG therapy * Ability to provide written informed consent
Exclusion criteria
* Hypersensitivity to components of Blad-Care * Contraindication to BCG therapy * Neurogenic bladder or significant urinary tract abnormalities * Severe renal dysfunction * Any condition considered unsuitable for study participation by the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in the combined Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI) score | Baseline (Week 0), after 3rd BCG instillation (Week 3), after 6th BCG instillation (Week 6), and 2 months after completion of BCG therapy (Week 14). | The ICSI and ICPI are validated scales to assess bladder symptoms and related problems. The combined score ranges from 0 to 31, where higher scores indicate worse symptoms and greater impact on quality of life. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Visual Analogue Scale (VAS) Score for Suprapubic Pain | Baseline (Week 0), after 3rd BCG instillation (Week 3), after 6th BCG instillation (Week 6), and 2 months after completion of BCG therapy (Week 14). | The Visual Analogue Scale (VAS) is used to measure the intensity of suprapubic pain experienced by the patient. It consists of a 10 cm (or 100 mm) horizontal line, where the left end represents "no pain" (score of 0) and the right end represents "worst imaginable pain" (score of 10). Patients mark a point on the line that corresponds to their pain level. Higher scores indicate greater pain intensity. The study evaluates the reduction in pain levels by comparing the mean change in VAS scores between the two groups (Group A vs. Group B) at each follow-up point compared to the baseline. |
| Incidence and Severity of Hematuria | From the first BCG instillation (Week 1) through 2 months after completion of BCG therapy (Week 14). | Hematuria severity is assessed using a graded scale to evaluate the safety and local side effects of BCG and Blad-Care™ therapy. Hematuria will be graded according to CTCAE version 5.0. |
| Incidence of Treatment-Emergent Adverse Events (TEAEs) | From the first BCG instillation (Week 1) through 2 months after completion of BCG therapy (Week 14). | To evaluate the safety and tolerability of Blad-Care™ when administered concurrently with or sequentially after BCG therapy. Adverse events include, but are not limited to, bladder irritation, urinary tract infection, severe hematuria, and systemic BCG infection. All adverse events will be graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The incidence and severity of these events will be compared between Group A and Group B. |
| BCG Treatment Completion Rate | From the date of the first BCG instillation (Week 1) through the date of the sixth BCG instillation (Week 6). | The BCG completion rate is defined as the percentage of participants who successfully receive all six planned weekly intravesical instillations of BCG therapy. A "completed" treatment is defined as receiving the full dose of BCG without permanent discontinuation due to treatment-related adverse events, disease progression, or patient withdrawal. This measure evaluates the tolerability of the combined treatment (Group A) compared to the sequential treatment (Group B). A higher rate indicates better clinical compliance and tolerability of the assigned regimen. |
| Incidence of Initiation of Additional Medications for Lower Urinary Tract Symptoms (LUTS) | From the first BCG instillation (Week 1) through 2 months after completion of BCG therapy (Week 14). | This measure evaluates the percentage of participants who require the initiation of new or additional medications to manage Lower Urinary Tract Symptoms (LUTS), such as alpha-blockers, anticholinergics, or beta-3 agonists, during the study period. BCG therapy often induces or exacerbates LUTS (urgency, frequency, pain); therefore, the need for rescue or supplemental medication serves as a clinical indicator of symptom severity and the efficacy of Blad-Care™ in replenishing the GAG layer. A lower incidence rate suggests better symptom control provided by the assigned study regimen. |
| Recurrence-Free Rate of Non-Muscle Invasive Bladder Cancer (NMIBC) | From the date of randomization until the study completion (June 2027, approximately 15 months). | This measure evaluates the percentage of participants who remain free of tumor recurrence during the follow-up period. Recurrence is defined as the histopathological confirmation of a new bladder tumor or the presence of a tumor during follow-up cystoscopy. Since the study involves high-risk NMIBC patients undergoing BCG therapy, monitoring the recurrence-free status ensures that the timing of Blad-Care™ administration (concurrent vs. sequential) does not negatively impact the oncological efficacy of the standard BCG treatment. |
Countries
South Korea
Contacts
CONTACTChunwoo Lee, M.D., Ph.D.
CONTACTJinsung Park, M.D., Ph.D.
PRINCIPAL_INVESTIGATORChunwoo Lee
Kyung Hee University Hospital
Outcome results
None listed