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

May 26, 2015 updated by: Enrico Finazzi Agro, University of Rome Tor Vergata

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: BCG alone (Immucist®)
Group A receive BCG (Immucist® 81 mg, Sanofi-Aventis Group) alone
Drug: BCG (Immucist®)
Usual BCG treatment
Other Names:
  • BCG
Experimental: Hyaluronic acid
Group B receive BCG and HA 40 mg (Cystistat, Mylan, Pittsburgh, PA, U.S.A.).
Drug: BCG (Immucist®)
Usual BCG treatment
Other Names:
  • BCG
Drug: Hyaluronic Acid
Add hyaluronic acid to BCG Treatment
Other Names:
  • Cystistat (Mylan, Pittsburgh, PA, U.S.A.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
Before and after six weeks of treatment (end of induction course)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Rome Tor Vergata

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2011

Primary Completion (Actual)

August 1, 2012

Study Completion (Actual)

August 1, 2012

Study Registration Dates

First Submitted

July 31, 2014

First Submitted That Met QC Criteria

August 1, 2014

First Posted (Estimate)

August 4, 2014

Study Record Updates

Last Update Posted (Estimate)

May 28, 2015

Last Update Submitted That Met QC Criteria

May 26, 2015

Last Verified

May 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EA-1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Poisoning by BCG Vaccine

Clinical Trials on BCG (Immucist®)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Lithuania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe