Poisoning by BCG VaccinePhase 2NCT02207608
Influence of Hyaluronic Acid on Bacillus Calmette-Guérin Local Side Effects
A Phase 2 study testing Hyaluronic Acid and BCG (Immucist®) in people with Poisoning by BCG Vaccine, run by University of Rome Tor Vergata.
Trial summary
The purpose of this study is to evaluate a possible role of intravesical Hyaluronic Acid in reducing local toxicity of Bacillus Calmette Guerin (BCG) used to treat bladder urothelial cell carcinoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Poisoning by BCG Vaccine
- What is being tested?
- Hyaluronic Acid and BCG (Immucist®)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- Sep 2011to Aug 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically proven non-muscle invasive bladder cancer;
- Indication to intravesical instillation of BCG according to EAU guidelines;
- Age > 18 years;
- Willingness, to participate to the study;
- Written informed consent.
Who cannot join
- Previous or ongoing BCG or different intravesical instillations;
- Urinary tract infections (UTI) or other known pathologies of the lower urinary tract;
- Indication for a radical cystectomy;
- Severe systemic disorders, including neurological pathologies, kidney, liver or heart failure;
- Contraindications to BCG use.
About this study
Official title: Pilot Study of Influence of Hyaluronic Acid (HA) on Bacillus Calmette-Guérin (BCG) Local Side Effects
The purpose of this study is to evaluate a possible role of intravesical Hyaluronic Acid in reducing local toxicity of Bacillus Calmette Guerin (BCG) used to treat bladder urothelial cell carcinoma.
Read the detailed description
Bacillus Calmette-Guérin (BCG) is considered the most effective treatment to increase disease-free interval and reduce progression of non-muscle invasive bladder cancer (NMIBC) [1]. Although considered safe, BCG can produce both local and systemic side effects leading to treatment discontinuation or interruption. The most common local side-effects of BCG intravesical instillations include cystitis, characterized by irritative voiding symptoms and hematuria, which occur in approximately 75% of all patients. More rarely, serious local adverse events as a result of BCG infection, such as symptomatic granulomatous prostatitis and epididymo-orchitis, might occur and require permanent discontinuation of BCG treatment. Systemic side-effects include flu-like symptoms, such as general malaise and fever, occuring in approximately 40% of patients. A high persistent fever might be related to BCG infection or sepsis. Local and systemic side-effects might lead to discontinue intravesical BCG treatment in approximately 20% of patients [2]. Up to 54% of the patients undergoing intravesical therapy with chemotherapeutic agents to treat superficial bladder tumours can be affected by nonbacterial cystitis [3].
Several solutions have been proposed to reduce the occurrence of side effects from BCG with the aim to limit BCG discontinuation and the concomitant discomfort during endovesical treatment. Some Authors have proposed to avoid BCG administration in case of TUR within previous 2 weeks, traumatic catheterization, macroscopic hematuria, urethral stenosis, active tuberculosis, prior Bacillus Calmette-Guérin sepsis, immuno-suppression or urinary tract infection [4]. Other procedures include the prophylactic administration of isoniazid [5] or ofloxacin [6,7] or usually involve BCG dose reductions [8]. In common practice antimicrobials, anticholinergics, anaesthetics and analgesics are often used to relieve patients' symptoms.
Glycosaminoglycan (GAG) substitution therapy is an emerging treatment of Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) and response rates between 30% and 80% have been described with intravesical administration of various GAGs (hyaluronic acid, pentosan polysulfate, heparin, chondroitin sulfate, and dimethyl sulfoxide) [9,10]. Few papers report the results of GAG substitution therapy in the treatment of radiation and chemical cystitis [9,10]. To our knowledge, to date, only two papers have described GAG use in the treatment of BCG local side effects; this papers show very good results, with significant reduction of lower urinary tract symptoms after intravesical administration of HA [11,12].
Aim of the present randomized pilot study was to evaluate if the sequential administration of HA and BCG could be safe in prevention of early recurrence and progression of bladder tumor, and safe in reduction of local side-effects in patients with high risk NMIBC.
- Conditions
- Poisoning by BCG Vaccine
- Being tested
- Hyaluronic Acid, BCG (Immucist®)
- Keywords
- BCG, hyaluronic acid, non-muscle invasive bladder cancer, non bacterial cystitis
- Medical subject headings
- Non-Muscle Invasive Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyaluronic AcidDrug
Also called Cystistat (Mylan, Pittsburgh, PA, U.S.A.)
Add hyaluronic acid to BCG Treatment
BCG (Immucist®)Drug
Also called BCG
Usual BCG treatment
| Study group | Role | What they receive |
|---|---|---|
| BCG alone (Immucist®) | Active comparator | Group A receive BCG (Immucist® 81 mg, Sanofi-Aventis Group) alone Receives: Drug: BCG (Immucist®) |
| Hyaluronic acid | Experimental | Group B receive BCG and HA 40 mg (Cystistat, Mylan, Pittsburgh, PA, U.S.A.). Receives: Drug: Hyaluronic Acid; Drug: BCG (Immucist®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Visual Analogue Scale for Pain
1 to 10 scale (1 minimum pain perceivable; 10 unbearable pain, as perceived by the patient)
Measured: Before and after six weeks of treatment (end of induction course)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2014 (estimated)
- Study startSep 2011
- Primary completionAug 2012
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Poisoning by BCG VaccineStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rome Tor Vergata
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Enrico Finazzi Agro, University of Rome Tor Vergata
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02207608
- Sponsor's protocol ID
- EA-1
- Status last verified
- May 2015
- First submitted
- 31 Jul 2014
- Last updated
- 28 May 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Topazio L, Miano R, Maurelli V, Gaziev G, Gacci M, Iacovelli V, Finazzi-Agro E. Could hyaluronic acid (HA) reduce Bacillus Calmette-Guerin (BCG) local side effects? Results of a pilot study. BMC Urol. 2014 Aug 13;14:64. doi: 10.1186/1471-2490-14-64.
PubMed 25123116
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Influence of Hyaluronic Acid (HA) on Bacillus Calmette-Guérin (BCG) Local Side Effects
- ClinicalTrials.gov ID
- NCT02207608
- Acronym / sponsor ID
- EA-1
- Conditions
- Poisoning by BCG Vaccine
- Keywords
- BCG, hyaluronic acid, non-muscle invasive bladder cancer, non bacterial cystitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of Rome Tor VergataUniversity, hospital or other
- Study start
- Sep 2011
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 4 Aug 2014 (estimated)
- Results
- Posted 28 May 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate a possible role of intravesical Hyaluronic Acid in reducing local toxicity of Bacillus Calmette Guerin (BCG) used to treat bladder urothelial cell carcinoma.
Detailed description
Bacillus Calmette-Guérin (BCG) is considered the most effective treatment to increase disease-free interval and reduce progression of non-muscle invasive bladder cancer (NMIBC) [1]. Although considered safe, BCG can produce both local and systemic side effects leading to treatment discontinuation or interruption. The most common local side-effects of BCG intravesical instillations include cystitis, characterized by irritative voiding symptoms and hematuria, which occur in approximately 75% of all patients. More rarely, serious local adverse events as a result of BCG infection, such as symptomatic granulomatous prostatitis and epididymo-orchitis, might occur and require permanent discontinuation of BCG treatment. Systemic side-effects include flu-like symptoms, such as general malaise and fever, occuring in approximately 40% of patients. A high persistent fever might be related to BCG infection or sepsis. Local and systemic side-effects might lead to discontinue intravesical BCG treatment in approximately 20% of patients [2]. Up to 54% of the patients undergoing intravesical therapy with chemotherapeutic agents to treat superficial bladder tumours can be affected by nonbacterial cystitis [3].
Several solutions have been proposed to reduce the occurrence of side effects from BCG with the aim to limit BCG discontinuation and the concomitant discomfort during endovesical treatment. Some Authors have proposed to avoid BCG administration in case of TUR within previous 2 weeks, traumatic catheterization, macroscopic hematuria, urethral stenosis, active tuberculosis, prior Bacillus Calmette-Guérin sepsis, immuno-suppression or urinary tract infection [4]. Other procedures include the prophylactic administration of isoniazid [5] or ofloxacin [6,7] or usually involve BCG dose reductions [8]. In common practice antimicrobials, anticholinergics, anaesthetics and analgesics are often used to relieve patients' symptoms.
Glycosaminoglycan (GAG) substitution therapy is an emerging treatment of Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) and response rates between 30% and 80% have been described with intravesical administration of various GAGs (hyaluronic acid, pentosan polysulfate, heparin, chondroitin sulfate, and dimethyl sulfoxide) [9,10]. Few papers report the results of GAG substitution therapy in the treatment of radiation and chemical cystitis [9,10]. To our knowledge, to date, only two papers have described GAG use in the treatment of BCG local side effects; this papers show very good results, with significant reduction of lower urinary tract symptoms after intravesical administration of HA [11,12].
Aim of the present randomized pilot study was to evaluate if the sequential administration of HA and BCG could be safe in prevention of early recurrence and progression of bladder tumor, and safe in reduction of local side-effects in patients with high risk NMIBC.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BCG alone (Immucist®) | Active comparator | Drug: BCG (Immucist®)Group A receive BCG (Immucist® 81 mg, Sanofi-Aventis Group) alone |
| Hyaluronic acid | Experimental | Drug: Hyaluronic Acid, Drug: BCG (Immucist®)Group B receive BCG and HA 40 mg (Cystistat, Mylan, Pittsburgh, PA, U.S.A.). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Histologically proven non-muscle invasive bladder cancer;
- Indication to intravesical instillation of BCG according to EAU guidelines;
- Age > 18 years;
- Willingness, to participate to the study;
- Written informed consent.
Key exclusion criteria (5 listed)
- Previous or ongoing BCG or different intravesical instillations;
- Urinary tract infections (UTI) or other known pathologies of the lower urinary tract;
- Indication for a radical cystectomy;
- Severe systemic disorders, including neurological pathologies, kidney, liver or heart failure;
- Contraindications to BCG use.
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 AcidAlso: Cystistat (Mylan, Pittsburgh, PA, U.S.A.)Add hyaluronic acid to BCG Treatment | Drug | Hyaluronic acid |
| BCG (Immucist®)Also: BCGUsual BCG treatment | Drug | BCG alone (Immucist®), Hyaluronic acid |
Primary outcome
Visual Analogue Scale for Pain
Time frame: Before and after six weeks of treatment (end of induction course)
1 to 10 scale (1 minimum pain perceivable; 10 unbearable pain, as perceived by the patient)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25123116Topazio L, Miano R, Maurelli V, Gaziev G, Gacci M, Iacovelli V, Finazzi-Agro E. Could hyaluronic acid (HA) reduce Bacillus Calmette-Guerin (BCG) local side effects? Results of a pilot study. BMC Urol. 2014 Aug 13;14:64. doi: 10.1186/1471-2490-14-64.
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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hyaluronic Acid and BCG (Immucist®) in people with Poisoning by BCG Vaccine, run by University of Rome Tor Vergata.
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: finished, as of the sponsor's last update on 28 May 2015. Status can change between updates, so confirm with the study contact before making plans.
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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Visual Analogue Scale for Pain (time frame: Before and after six weeks of treatment (end of induction course)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02207608, which also lists 1 linked publication.
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 28 May 2015.