Clinical trial NCT04148677: Protoves M1® Syrup in Controlling Adverse Event During HIVEC® Instillations
Official title: The Role of Protopine Associated With Nuciferine (Protoves M1® Syrup) in Controlling Adverse Event During HIVEC® Instillations
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Bladder Cancer
LUTS
Pain
Lead sponsor: Cardarelli Hospital
Sponsor class: OTHER
First posted: 2019-11-01
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All patients who referred to a general hospital to receive endoscopic treatment for bladder cancer (TURB) and then the endovescical chemioprofilaxis.

Brief summary: 100 patients with bladder cancer whose underwent Hyperthermic Intravesical Chemotherapy (HIVEC®) will be randomized in two groups (Group A: PROTOVES M1 SYRUP, Group B: NO TREATMENT). The aim of this study will be to analyse the role of two alkaloid, Protopine and Nuciferine (Protoves-M1 ®) in the prevention and the treatment of the low and mild grade adverse events related to the use of HIVEC® instillations.

Detailed description: 100 patients with bladder cancer whose underwent Hyperthermic Intravesical Chemotherapy (HIVEC®) will be randomized in two groups (Group A: PROTOVES M1 SYRUP, Group B: NO TREATMENT). The aim of this study will be to analyse the role of two alkaloid, Protopine and Nuciferine (Protoves-M1 ®) in the prevention and the treatment of the low and mild grade adverse events related to the use of HIVEC® instillations.

At the baseline data on demographic and anthropometric features (age, weight, height, BMI), lifestyle characteristics (smoke, alcohol), any comorbidities (hypertension, diabetes mellitus, etc.) will be collected. All patients will be undergone to a clinical evaluation (comprised general, genital and urologic examination). Before starting the treatment, the following measurements will be collected: prostate volume by transrectal ultrasound, PSA, uroflowmetry (Qmax, Volume Voided, Post-Void Residual), IPSS (International Prostatic Symptoms Score) questionnaire, OverActive Bladder questionnaire-short form (OABq-SF) 6 and 13, patient perception of intensity of urgency scale (PPIUS), and visual analogue scale (VAS). PSA and IPSS will be investigated only in male pts. In addition, the patient impression of improvement will be assessed. Improvement will be evaluated with the Patient Global Impression of Improvement questionnaire (PGI-I), a validated tool to estimate the improvement or the deterioration associated to the treatment.

The primary endpoint was the evaluation of the efficacy of the therapy with Protoves-M1 in controlling of the irritative symptoms, including nocturia, urinary frequency, bladder pain, urgency and urge incontinence related to the chemo-hyperthermia treatment. The secondary endpoint evaluated was the influences of the treatment on the uroflowmetric parameters.

After 1 and 6 weeks of therapy all patients will be undergone to a clinical and instrumental evaluation : Uroflow-Qmax (ml/s), Uroflow-Volume voided (ml),Uroflow-RPM (ml), IPSS total, OAB-q SF 6, OAB-q SF 13, PPIUS, PGI-I, VAS scale will be collected.

Eligibility criteria: Inclusion Criteria:

* Intermediate-and high-risk NMIBC (non-muscle invasive bladder cancer) patients.
* Therapeutic program of HIVEC® (Recirculant hyperthermic IntraVEsical chemotherapy).
* Must be able to drink a syrup.

Exclusion Criteria:

* Uncontrolled underlying diseases (ASA III or IV)
* Post void residual urine ≥ 100 ml
* Bleeding tendency
* Drug abuse
* Chronic pelvic pain
* Urinary tract infection
* Neurological disease
* Bladder lithiasis
* Renal or liver failure
* Tachycardia and heart failure.
* Male patients with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH)with abnormal values of uroflowmetry
* Male patients with lower urinary tract symptoms (LUTS) that assume medical treatment for BPH.

Primary outcomes:
measure: IPSS total
timeFrame: 1 and 6 weeks
measure: OAB-q SF 6
timeFrame: 1 and 6 weeks
measure: OAB-q SF 13
timeFrame: 1 and 6 weeks
measure: PPIUS
timeFrame: 1 and 6 weeks
measure: PGI-1
timeFrame: 1 and 6 weeks
measure: VAS scale
timeFrame: 1 and 6 weeks
Secondary outcomes:
measure: Qmax
timeFrame: 1 and 6 weeks
measure: Volume voided
timeFrame: 1 and 6 weeks
measure: RPM
timeFrame: 1 and 6 weeks
Other outcomes:
Locations:
Study officials:
affiliation: AORN A.Cardarelli Urology Department
name: Francesco Chiancone
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sousa A, Pineiro I, Rodriguez S, Aparici V, Monserrat V, Neira P, Carro E, Murias C, Uribarri C. Recirculant hyperthermic IntraVEsical chemotherapy (HIVEC) in intermediate-high-risk non-muscle-invasive bladder cancer. Int J Hyperthermia. 2016 Jun;32(4):374-80. doi: 10.3109/02656736.2016.1142618. Epub 2016 Feb 25.
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citation: Wang MX, Zhao XJ, Chen TY, Liu YL, Jiao RQ, Zhang JH, Ma CH, Liu JH, Pan Y, Kong LD. Nuciferine Alleviates Renal Injury by Inhibiting Inflammatory Responses in Fructose-Fed Rats. J Agric Food Chem. 2016 Oct 26;64(42):7899-7910. doi: 10.1021/acs.jafc.6b03031. Epub 2016 Oct 18.
citation: Dmochowski R. Antimuscarinic therapy in men with lower urinary tract symptoms: what is the evidence? Curr Urol Rep. 2006 Nov;7(6):462-7. doi: 10.1007/s11934-006-0055-4.