Urinary Bladder NeoplasmsPRO-GAGNCT07495072
Early vs Delayed Intravesical Blad-Care During BCG Therapy
A study testing Hyaluronic Acid and Chondroitin Sulfate (Blad-Care™) in people with Urinary Bladder Neoplasms and BCG-Induced Cystitis, run by BLAD-HYA Group at 1 site in South Korea.
Trial 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… Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Urinary Bladder Neoplasms, BCG-Induced Cystitis
- What is being tested?
- Hyaluronic Acid and Chondroitin Sulfate (Blad-Care™)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteSouth Korea
- Study dates
- 3 Nov 2025to Jun 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
South Korea1 site, 1 recruiting
- Recruiting
Kyung Hee University Hospital
Seoul, Dongdaemun-gu, 02447
Chunwoo Lee, M.D., Ph.D., 821034133542, lcw200@hanmail.net
About this study
Official title: 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.
Read the 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.
- Conditions
- Urinary Bladder Neoplasms, BCG-Induced Cystitis
- Being tested
- Hyaluronic Acid and Chondroitin Sulfate (Blad-Care™)
- Keywords
- Hyaluronic Acid, BCG-induced Cystitis, BCG-related Bladder Pain, Non-Muscle Invasive Bladder Cancer (NMIBC), Interstitial Cystitis
- Medical subject headings
- Urinary Bladder Neoplasms, Non-Muscle Invasive Bladder Neoplasms, Cystitis, Interstitial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyaluronic Acid and Chondroitin Sulfate (Blad-Care™)Drug
Also called Sodium Hyaluronate and Chondroitin Sulfate, Blad-Care, HA-CS combination, GAG layer replenisher
Intravesical instillation of a sterile solution containing sodium hyaluronate and chondroitin sulfate designed to restore the urothelial glycosaminoglycan (GAG) layer.
| Study group | Role | What they receive |
|---|---|---|
| Group A (Early Blad-Care Administration) | Experimental | 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). Receives: Drug: Hyaluronic Acid and Chondroitin Sulfate (Blad-Care™) |
| Group B (Delayed Blad-Care Administration) | Active comparator | 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. Receives: Drug: Hyaluronic Acid and Chondroitin Sulfate (Blad-Care™) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 outcomes (6)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From the date of randomization until the study completion (June 2027, approximately 15 months).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2026
- Study start3 Nov 2025
- Primary completionDec 2026 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Urinary Bladder NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- None (open label)
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- BLAD-HYA Group
- Sponsor type
- University, hospital or other
- Collaborators
- Eulji University
- Responsible party
- Principal investigator, Chunwoo Lee, Kyung Hee University Hospital
- Investigators
- Chunwoo Lee, Principal investigator, Kyung Hee University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07495072
- Sponsor's protocol ID
- EMC-KHMC-URO-2025
- Other IDs
- KHUH 2025-11-064-002
- Acronym
- PRO-GAG
- Status last verified
- Mar 2026
- First submitted
- 13 Mar 2026
- Last updated
- 27 Mar 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The individual participant data will not be shared to protect the privacy of the participants and due to institutional data policy.
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimal Timing of Intravesical GAG Restoration Therapy for BCG-Induced Bladder Toxicity in Patients With Non-Muscle-Invasive Bladder Cancer: A Prospective Randomized Study
- ClinicalTrials.gov ID
- NCT07495072
- Acronym / sponsor ID
- PRO-GAG / EMC-KHMC-URO-2025
- Conditions
- Urinary Bladder Neoplasms, BCG-Induced Cystitis
- Keywords
- Hyaluronic Acid, BCG-induced Cystitis, BCG-related Bladder Pain, Non-Muscle Invasive Bladder Cancer (NMIBC), Interstitial Cystitis
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 56 participants (estimated)
- Lead sponsor
- BLAD-HYA GroupUniversity, hospital or other
- Collaborators
- Eulji University
- Study start
- 3 Nov 2025 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Jun 2027 (estimated)
- First posted
- 27 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Group A (Early Blad-Care Administration) | Experimental | Drug: Hyaluronic Acid and Chondroitin Sulfate (Blad-Care™)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). |
| Group B (Delayed Blad-Care Administration) | Active comparator | Drug: Hyaluronic Acid and Chondroitin Sulfate (Blad-Care™)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. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hyaluronic Acid and Chondroitin Sulfate (Blad-Care™)Also: Sodium Hyaluronate and Chondroitin Sulfate, Blad-Care, HA-CS combination, GAG layer replenisherIntravesical instillation of a sterile solution containing sodium hyaluronate and chondroitin sulfate designed to restore the urothelial glycosaminoglycan (GAG) layer. | Drug | Group A (Early Blad-Care Administration), Group B (Delayed Blad-Care Administration) |
Primary outcome
Change from baseline in the combined Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI) score
Time frame: 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.
6 secondary outcomes
Change from Baseline in Visual Analogue Scale (VAS) Score for Suprapubic Pain
Time frame: 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
Time frame: From the first BCG instillation (Week 1) through 2 months after completion of BCG therapy (Week 14).
Incidence of Treatment-Emergent Adverse Events (TEAEs)
Time frame: From the first BCG instillation (Week 1) through 2 months after completion of BCG therapy (Week 14).
BCG Treatment Completion Rate
Time frame: 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)
Time frame: 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)
Time frame: From the date of randomization until the study completion (June 2027, approximately 15 months).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2026.
- Individual participant dataSharing planned: No. The individual participant data will not be shared to protect the privacy of the participants and due to institutional data policy.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Chunwoo Lee principal investigator
Kyung Hee University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hyaluronic Acid and Chondroitin Sulfate (Blad-Care™) in people with Urinary Bladder Neoplasms and BCG-Induced Cystitis, run by BLAD-HYA Group at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Chunwoo Lee, M.D., Ph.D. (+8229588897, lcw200@hanmail.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in the combined Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI) score (time frame: 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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2026.