Effects of Microcrystalline Titanium Dioxide With Covalently Linked Monovalent Silver Ions on Complications After Total Hysterectomy

Study Overview
=================
Brief Summary
-----------------
Total hysterectomy is one of the most performed surgical procedures in the world and it is associated with post-operative complications. The postoperative morbidity rate is estimated to vary from 3% to 8% with a readmission rate of 5-7%. The most frequent postoperative complications are urinary tract infections, wound infection of the vaginal vault, vault cellulitis, bleeding, suture dehiscence, pelvic abscess. The introduction of routine antibiotic prophylaxis has significantly reduced the risk of infectious complications, which however remains higher than other clean surgery, mainly due to contamination by the vaginal bacterial flora. In this scenario, the introduction of adjuvant factors acting on bacterial flora, can contribute to reduce the risk of post-surgical complications. The cationic silver ions (Ag +) stabilized by covalent link with Titanium dioxide (TiO2), the TIAB, maximizes the properties of silver by optimizing the antibiotic action and disruptive properties of the pathogenic biofilm of bacteria and fungi. Thanks to these properties, TIAB is able to enhance the antibiotic action by reducing the risk of antibiotic resistance and recurrent infections linked to the biofilm. Re-establishing the optimal vaginal microenvironment represents a fundamental step reducing the risk of infections in the surgical site, since the vagina is a non-sterile environment populated by bacterial species that can generate biofilm and potentially infect the site of surgery. In addition to microbicidal and disruptive biofilm activity, TIAB has demonstrated a direct action on tissue regeneration processes by stimulating the production of collagen and its modeling. Different clinical trials have reported a cicatrizing and re-epithelializing action of TIAB administered vaginally in the context of cervical conization for pathology related to HPV. Without showing any notable adverse effects or a negative action on lactobacillary flora with an overall good therapy tolerance by patients. On the basis of the available evidence, we conduct a randomized controlled clinical trial to determine if TIAB treatment in the formulation of vaginal capsules TIAGIN (TIAB (microcrystalline titanium dioxide with covalently linked monovalent silver ions), Sodium Hyaluronate, Aloe Barbadensis Extract) is able to reduce the incidence of infectious complications, that are related to altered healing of post-hysterectomy vaginal suture.

Official Title
-----------------
Randomized Controlled Trial on the Use of Microcrystalline Titanium Dioxide With Covalently Linked Monovalent Silver Ions (TIAB) in the Formulation of Vaginal Capsules in the Prevention of Complications After Total Hysterectomy

Conditions
-----------------
Infection, Bleeding, Complication, Postoperative

Intervention / Treatment
-----------------
* Other: TIAB: microcrystalline titanium dioxide with covalently linked monovalent silver ions
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women underwent laparoscopic total hysterectomy for benign gynecological pathology Exclusion Criteria: Women underwent non-laparoscopic total hysterectomy Women underwent laparoscopic total hysterectomy for malignant pathology Patients with diabetes mellitus in insulin therapy Smoking patients Patients suffering from chronic rheumatic diseases or chronic diseases not in adequate control.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled double-blind trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TIAB treatment<br>From the first postoperative day for ten days, single vaginal capsule per day of TIAB (microcrystalline titanium dioxide with covalently linked monovalent silver ions), Sodium Hyaluronate, and Aloe Barbadensis Extract vaginal capsule. | Other: TIAB: microcrystalline titanium dioxide with covalently linked monovalent silver ions<br>* TIAGIN vaginal capsule, composition: TIAB (microcrystalline titanium dioxide with covalently linked monovalent silver ions), Sodium Hyaluronate, Aloe Barbadensis Extract<br>|
| Placebo Comparator: Placebo<br>From the first postoperative day for ten days, single vaginal capsule per day of sodium Hyaluronate, and Aloe Barbadensis Extract vaginal capsule. | Other: Placebo<br>* Placebo vaginal capsule, composition: Sodium Hyaluronate, Aloe Barbadensis Extract<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaginal bleeding | at least one episode of red vaginal blood loss | Between the 10th post operative day and the 30th post operative day | 
| Vaginal vault infection | at least one episode of inflammation and infection in the vaginal vault suture requiring antibiotic therapy | Between the first post operative day and the 30th post operative day | 
| Urinary tract infection | at least one episode of signs and symptoms requiring empiric antibiotic therapy | Between the 10th post operative day and the 30th post operative day | 
| Dehiscence of vaginal vault suture | Dehiscence of vaginal vault suture requiring repeat surgery | Between the 10th post operative day and the 30th post operative day | 
| Readmission | At least one episode of readmission related to postoperative complications | Between the day of discharge and the 30th post operative day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Adverse events due to the use of vaginal capsule therapy: erythema, vaginal and vulvar pruritus, dermatitis. | Between the first post operative day and the 30th post operative day |