Early vs Delayed Intravesical Blad-Care During BCG Therapy (PRO-GAG)

Optimal Timing of Intravesical GAG Restoration Therapy for BCG-Induced Bladder Toxicity in Patients With Non-Muscle-Invasive Bladder Cancer: A Prospective Randomized Study

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.

Study Overview

• Status: Recruiting
• Conditions: Urinary Bladder Neoplasms; BCG-Induced Cystitis
• Intervention / Treatment: Drug: Hyaluronic Acid and Chondroitin Sulfate (Blad-Care™)

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.

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chunwoo Lee, M.D., Ph.D.; Phone Number: +8229588897; Email: lcw200@hanmail.net
• Study Contact Backup: Name: Jinsung Park, M.D., Ph.D.; Phone Number: +8229588896; Email: jspark.uro@gmail.com

Study Locations

• South Korea
  • Dongdaemun-gu
    • Seoul, Dongdaemun-gu, South Korea, 02447
      • Recruiting
      • Kyung Hee University Hospital
      • Contact: Chunwoo Lee, M.D., Ph.D.; Phone Number: 821034133542; Email: lcw200@hanmail.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A (Early Blad-Care Administration); Patients receive intravesical BCG once weekly for six weeks. Beginning with the fourth BCG instillation, intravesical Blad-Care is administered immediately after BCG instillation for three consecutive weeks (weeks 4-6).	Drug: Hyaluronic 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.; Other Names: Sodium Hyaluronate and Chondroitin Sulfate; Blad-Care; HA-CS combination; GAG layer replenisher
Active Comparator: Group B (Delayed Blad-Care Administration); Patients receive intravesical BCG once weekly for six weeks. Blad-Care is administered after completion of the BCG induction course and repeated weekly for three consecutive weeks.	Drug: Hyaluronic 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.; Other Names: Sodium Hyaluronate and Chondroitin Sulfate; Blad-Care; HA-CS combination; GAG layer replenisher

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the combined Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI) score	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.	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).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Visual Analogue Scale (VAS) Score for Suprapubic Pain	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.	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).
Incidence and Severity of Hematuria	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.	From the first BCG instillation (Week 1) through 2 months after completion of BCG therapy (Week 14).
Incidence of Treatment-Emergent Adverse Events (TEAEs)	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.	From the first BCG instillation (Week 1) through 2 months after completion of BCG therapy (Week 14).
BCG Treatment Completion Rate	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.	From the date of the first BCG instillation (Week 1) through the date of the sixth BCG instillation (Week 6).
Incidence of Initiation of Additional Medications for Lower Urinary Tract Symptoms (LUTS)	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.	From the first BCG instillation (Week 1) through 2 months after completion of BCG therapy (Week 14).
Recurrence-Free Rate of Non-Muscle Invasive Bladder Cancer (NMIBC)	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.	From the date of randomization until the study completion (June 2027, approximately 15 months).

Collaborators and Investigators

• Sponsor: BLAD-HYA Group
• Collaborators: Eulji University
• Investigators: Principal Investigator: Chunwoo Lee, Kyung Hee University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: March 13, 2026
• First Submitted That Met QC Criteria: March 21, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 21, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Hyaluronic Acid; Interstitial Cystitis; Non-Muscle Invasive Bladder Cancer (NMIBC); BCG-induced Cystitis; BCG-related Bladder Pain
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Carcinoma; Urinary Bladder Diseases; Cystitis; Non-Muscle Invasive Bladder Neoplasms; Urinary Bladder Neoplasms; Cystitis, Interstitial; Carbohydrates; Glycosaminoglycans; Polysaccharides; Chondroitin; Hyaluronic Acid; Chondroitin Sulfates; chondroitin sulfate, sodium hyaluronate drug combination
• Other Study ID Numbers: EMC-KHMC-URO-2025; KHUH 2025-11-064-002 (Other Identifier: Kyung Hee University Hospital Institutional Review Board)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The individual participant data will not be shared to protect the privacy of the participants and due to institutional data policy.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No