Influence of Hyaluronic Acid on Bacillus Calmette-Guérin Local Side Effects

NCT ID: NCT02207608

Last Updated: 2015-05-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2012-08-31

Brief 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BCG alone (Immucist®)

Group A receive BCG (Immucist® 81 mg, Sanofi-Aventis Group) alone

Group Type: ACTIVE_COMPARATOR

BCG (Immucist®)

Intervention Type: DRUG

Usual BCG treatment

Hyaluronic acid

Group B receive BCG and HA 40 mg (Cystistat, Mylan, Pittsburgh, PA, U.S.A.).

Group Type: EXPERIMENTAL

Hyaluronic Acid

Intervention Type: DRUG

Add hyaluronic acid to BCG Treatment

BCG (Immucist®)

Intervention Type: DRUG

Usual BCG treatment

Interventions

Hyaluronic Acid

Add hyaluronic acid to BCG Treatment

Intervention Type: DRUG

BCG (Immucist®)

Usual BCG treatment

Intervention Type: DRUG

Other Intervention Names

Cystistat (Mylan, Pittsburgh, PA, U.S.A.); BCG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Rome Tor Vergata

OTHER

Sponsor Role: lead

Responsible Party

Enrico Finazzi Agro

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

References

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.

Reference Type: DERIVED

PMID: 25123116 (View on PubMed)

Other Identifiers

EA-1

Identifier Type: -

Identifier Source: org_study_id