Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02207608 |
| Other study ID # |
EA-1 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2
|
| First received |
July 31, 2014 |
| Last updated |
May 26, 2015 |
| Start date |
September 2011 |
| Est. completion date |
August 2012 |
Study information
| Verified date |
May 2015 |
| Source |
University of Rome Tor Vergata |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Italy: National Institute of Health |
| Study type |
Interventional
|
Clinical 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.
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.
