Sponsor decision

This will be an open-label, prospective, single-centre, randomised, controlled, parallel-group medical device investigation. The investigational plan will include four visits in total at the investigational site. One visit (Visit 2) will consist in the hospitalisation period and will last 3/4 days. Patients will be admitted to hospital in the day preceding the TURBT (Day -1; in case the TURBT is programmed in the morning) or in the day of the TURBT (Day 0; in case the TURBT is programmed in the afternoon) and will stay in the hospital for 3/4 days after the intervention (performed on Day 0). Patients will then be discharged, if considered as appropriate based on Investigator's judgment, following the removal of the catheter and the first clear urination. Patients will be asked to remain in the same geographic area of the investigational site up to the end of study visit.

The following visits/activities will be performed:

• Visit 1: the screening visit will be performed between 60 and 14 days before the TURBT (Day -60/-14);
• Visit 2 (hospitalisation): patients will be admitted to hospital in the day preceding the TURBT or in the day of the TURBT and will be randomised to the assigned treatment group. TURBT will be performed on Day 0. The first treatment with the investigational device will be performed within 6 hours from the end of TURBT. The catheter will be removed at Day 2 ± 1 if considered as appropriate based on Investigator's judgment, following the first clear urination). The second treatment with the investigational device will be performed just before the removal of the catheter and the discharge from hospital.
• Visit 3: a follow-up visit will be performed at Day 5 ± 1 (i.e. 3 days after catheter removal);
• Visit 4: the end of study visit will be performed at Day 25 ± 4.

Inclusion Criteria:

1. Males and females patients aged ≥ 18 years old;

2. Patients with suspected clinical diagnosis of primary or secondary single or multiple, any size, NMIBC scheduled for TURBT;

3. Female patients with child-bearing potential must not be pregnant or lactating, and willing to use adequate contraception for the duration of study. Note: to be considered females of non-child-bearing potential, females must be surgically sterile or postmenopausal as documented in medical history for at least 1 year.

   Highly effective birth control methods include: combined hormonal contraception (containing estrogens and progestogen) associated with inhibition of ovulation (oral, intravaginal, transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomised partner; sexual abstinence.

4. Patients available to remain in the same geographical area of the investigational site from the hospitalisation to the end of the investigation;

5. Patients able to understand and comply with the requirements of the study and voluntarily provide written informed consent.

Exclusion Criteria:

1. Patients with Schistosoma haematobium infestation or neurologenic bladder;
2. Patients having received (in the three months before the screening) previous treatment with neurotoxic drugs (e.g. vanilloids, ovanil, botulinum toxin, etc.) or pelvic irradiation, which could interfere with sensory functions;
3. Patients with indication for early instillation due to new treatment guideline;
4. Patients with any potential interfering factors for LUTS evaluation, such as obstruction, nocturnal polyuria strictures, neurogenic bladder, detrusor over/under capacity;
5. Patients with clinically relevant comorbidities that could potentially interfere with study evaluations, such as diabetes, renal disease and cardiac failure;
6. Patients with presence of other serious gastrointestinal, renal, hepatic, pulmonary, cardiovascular or neurological disease that could adversely affect the safety of the study treatment or the patient's ability to comply with investigation requirements;
7. Patients on treatment or having received (in 30 days before screening) the following anticholinergic drugs: oxybutinin, tolterodine, fesoterodine, darifenacin, trospium and beta-3 adrenoreceptor agonist;
8. Patients with known or suspected allergy, hypersensitivity or intolerance to hyaluronic acid and/or any other component of the investigational device;
9. Patients with hypersensitivity to local anaesthetics or other drugs used for the procedure;
10. Women who are pregnant or breastfeeding or women who could become pregnant and are not using effective contraception;
11. Patients unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the investigation;
12. Patients who have used any investigational drug or device in an investigational protocol in the past 3 months;
13. Patients who have been previously enrolled in this investigation.