Feasibility and Safety of the Calcium Alginate Hydrogel Sealant for the Treatment of Cryptoglandular Fistula-in-ano: Phase I/IIa Clinical Trial

Study Overview
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Brief Summary
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Background: Complex perianal fistulas pose a challenge to surgeons since the fistulous tract must be eliminated without impairing continence. Biological sealants have emerged as an effective alternative for maintaining the integrity of the anal sphincter. The investigators aimed to assess the feasibility and safety of calcium alginate hydrogel injections into the tract as treatment for complex cryptoglandular fistulas. Methods: A prospective, single-center, case series of this novel technique was conducted in a level 3 hospital, including patients diagnosed with trans-sphincteric perianal fistulas and treated with a calcium alginate hydrogel sealant. A strict follow-up was performed by an independent surgeon at 1, 3, 6, and 12 months. The main outcome measures were feasibility, safety (number of adverse events) and efficacy of the treatment.

Official Title
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Feasibility and Safety of the Calcium Alginate Hydrogel Sealant for the Treatment of Cryptoglandular Fistula-in-ano

Conditions
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Anal Fistula

Intervention / Treatment
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* Procedure: Calcium alginate hydrogel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Informed Consent Form Age ≥18 years Cryptoglandular PAF treated by Seton placement for at least 3 months, with a single External Fistulous Orifice and Internal Fistulous Orifice Exclusion Criteria: Informed Consent Form not signed or withdrawn Not possible to adhere to follow-up routine Another investigational drug in the previous 3 months Allergy to alginate Grade IV in American Society of Anesthesiologists scale Pregnancy History of radiotherapy in the perineal area Diagnosis or suspicion of Intestinal Blow Disease Immunosuppression, active neoplasia at the time of recruitment or in previous year, or positive for human immunodeficiency virus Internal Fistulous Orifice not located during the procedure Simple anal fistula (submucosa or low Intersphincteric Perianal Fistula, except association with Faecal Incontinence Anal stenosis that prevents exploration Undrained collections >2 cm Rectovaginal fistulas Fistulas of non-cryptoglandular origin

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

| Intervention/Treatment |
| --- |
|Procedure: Calcium alginate hydrogel|The external and internal fistulous orifice and fistulous tract were explored without applying any product, including hydrogen peroxide or povidone-iodine. The seton was removed and FT cannulation was performed using a needle for cleaning with a gauze impregnated with saline. Calcium chloride was applied through the EFO until it exits through the IFO, and then the IFO was obturated. Alginate was applied, and the pressure at the IFO was stopped, until the alginate solution partial exits through the IFO. The IFO was closed with a 3/0 braided resorbable suture. The EFO was removed with an electric scalpel and closed with a 3/0 braided resorbable suture.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of patients treated following the protocol during the surgery | Feasibility is measured as the ratio between the number of patients who received the injection following all the steps of the protocol and the total number of individuals included in the study. | During the surgery | 
| Incidence of adverse events at 1 month | Incidence of adverse events, their relationship to the product under investigation, and their intensity (mild, moderate, or severe) | At 1 month | 
| Incidence of adverse events at 3 months | Incidence of adverse events, their relationship to the product under investigation, and their intensity (mild, moderate, or severe) | At 3 months | 
| Incidence of adverse events at 6 months | Incidence of adverse events, their relationship to the product under investigation, and their intensity (mild, moderate, or severe) | At 6 months | 
| Incidence of adverse events at 12 months | Incidence of adverse events, their relationship to the product under investigation, and their intensity (mild, moderate, or severe) | At 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ecographic curation at 12 months | Closure of the external fistulous orifice that prevented the injection of hydrogen peroxide diluted to 50 percent, in addition to the absence of hyperechogenic collections and images suggesting the existence of pus or air in the tract. | At 12 months | 
| Clinical curation at 1 month | Complete cure defined as the absence of suppuration and scarring in the external fistulous orifice; partial cure defined as the absence of suppuration and scarring in the external fistulous orifice without complete re-epithelialization; treatment failure or lack of cure defined as suppuration and/or scarring in the external fistulous orifice | At 1 month | 
| Clinical curation at 3 months | Complete cure defined as the absence of suppuration and scarring in the external fistulous orifice; partial cure defined as the absence of suppuration and scarring in the external fistulous orifice without complete re-epithelialization; treatment failure or lack of cure defined as suppuration and/or scarring in the external fistulous orifice | At 3 months | 
| Clinical curation at 6 months | Complete cure defined as the absence of suppuration and scarring in the external fistulous orifice; partial cure defined as the absence of suppuration and scarring in the external fistulous orifice without complete re-epithelialization; treatment failure or lack of cure defined as suppuration and/or scarring in the external fistulous orifice | At 6 months | 
| Clinical curation at 12 months | Complete cure defined as the absence of suppuration and scarring in the external fistulous orifice; partial cure defined as the absence of suppuration and scarring in the external fistulous orifice without complete re-epithelialization; treatment failure or lack of cure defined as suppuration and/or scarring in the external fistulous orifice | At 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cryptoglandular anal fistula, calcium alginate, sealant