Protoves M1® Syrup in Controlling Adverse Event During HIVEC® Instillations

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Role of Protopine Associated With Nuciferine (Protoves M1® Syrup) in Controlling Adverse Event During HIVEC® Instillations

Conditions
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Bladder Cancer, LUTS, Pain

Intervention / Treatment
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* Dietary Supplement: Protoves M1®


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Protoves M1® syrup<br>A combination of two alkaloid, Protopine and Nuciferine | Dietary Supplement: Protoves M1®<br>* A combination of two alkaloid, Protopine and Nuciferine (Protoves-M1 ®)<br>|
| No treatment<br>Patients will not receive a treatment | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IPSS total | The International Prostate Symptom Score (I-PSS) is based on the answers to some questions concerning urinary symptoms and one question concerning quality of life. | 1 and 6 weeks | 
| OAB-q SF 6 | The OAB-q SF 6 is a questionnaire developed to evaluate the overactive bladder symptom and health-related quality of life. | 1 and 6 weeks | 
| OAB-q SF 13 | The OAB-q SF 6 is a questionnaire developed to evaluate the overactive bladder symptom and health-related quality of life. | 1 and 6 weeks | 
| PPIUS | The PPIUS is a questionnaire developed to evaluate the patient perception of intensity of urgency | 1 and 6 weeks | 
| PGI-1 | PGI-I is a validated tool to estimate the improvement or the deterioration associated to the treatment. | 1 and 6 weeks | 
| VAS scale | Visual analogue scales (VAS) are 10-cm lines anchored at the ends by words that define the bounds of various pain dimensions. | 1 and 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Qmax | Qmax (ml/s) is the maximum flow rate at uroflowmetry | 1 and 6 weeks | 
| Volume voided | Volume voided (ml) at uroflowmetry | 1 and 6 weeks | 
| RPM | Post-Void residual (ml) measures the amount of urine left in the bladder after urination. | 1 and 6 weeks |