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Treatment of Complex Anal Fistulas Using Centrifuged Adipose Tissue Containing Progenitor Cells (CAT)

Primary Purpose

Anal Fistula

Status
Completed
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Autologous centrifuged adipose tissue (CAT) injection after anal fistulectomy
Sponsored by
University Hospital of Ferrara
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anal Fistula focused on measuring complex fistula-in ano, adipose tissue, stem cell therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Patients aged 18 years or older with complex perianal fistulas

Exclusion Criteria:

Inflammatory bowel diseases, Crohn's Disease (CD) or Ulcerative Colitis (UC) Hepatitis B or C virus Infection with Human immunodeficiency virus Surgery for a malignant tumor during the previous 5 years (excluding in situ carcinoma) Previous pelvic radiotherapy Autoimmune disease Active tuberculosis Symptoms of septicemia Breastfeeding or pregnant women Women unwilling to use contraception during the study Psychiatric disorders Alcoholism Drug dependency Allergy to local anesthetics

Sites / Locations

  • Simona Ascanelli

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

CAT injection group

No CAT injection group

Arm Description

After fistulectomy for complex anal fistula, CAT (harvested from abdominal subcutaneous adipose tissue by Coleman's procedure) was injected into the tissue surrounding the internal opening, and inside the perianal wound obtained after fistulectomy.

Patients of this group were treated with anal fistulectomy without CAT injection.

Outcomes

Primary Outcome Measures

Fistula healing rate within 6 months after surgery
Fistula healing was defined as the absence of any anal symptom, with no discharge from the fistula and a closed external opening confirmed on clinical evaluation. Fistula healing was eventually confirmed by a pelvic MRI at 3 months after surgery

Secondary Outcome Measures

Safety of autologous adipose tissue injection
Safety was evaluated by the overall incidence and severity of Adverse Events (AEs) up to 4 weeks following surgery.

Full Information

First Posted
March 25, 2020
Last Updated
March 27, 2020
Sponsor
University Hospital of Ferrara
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1. Study Identification

Unique Protocol Identification Number
NCT04326907
Brief Title
Treatment of Complex Anal Fistulas Using Centrifuged Adipose Tissue Containing Progenitor Cells
Acronym
CAT
Official Title
Efficacy and Safety of Treatment of Complex Anal Fistulas Not Associated With Crohn's Disease Using Centrifuged Adipose Tissue Containing Progenitor Cells: a Randomized Controlled Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
May 1, 2016 (Actual)
Primary Completion Date
May 1, 2019 (Actual)
Study Completion Date
October 1, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital of Ferrara

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
In the treatment of complex anal fistulas transplant of freshly collected autologous adipose tissue mechanically fragmented or centrifuged adipose tissue (CAT) might be an alternative to in vitro expanded autologous or allogeneic adipose-derived stem cells, showing remarkable efficacy in diverse therapeutic indications. The aim of our study is to evaluate randomly the efficacy and safety of the use of CAT in the healing process of complex anal fistulas, except for Crohn's disease (CD) related fistulas.
Detailed Description
This monocentric randomized controlled study was designed to test the efficacy and safety of injection of CAT for treatment of complex fistula-in ano, not associated with CD . The study was conducted at the Second Surgical Unit of the University Hospital of Ferrara, located in the North East of Italy. All consecutive patients referred to our clinic with complex anal fistula were screened. Patients were enrolled from May 2016 through May 2019. Eligible patients were randomly assigned, according to a 1:1 scheme, to receive treatment with or without CAT (120 patients totally). The primary endpoint was defined as the proportion of patients whose fistula was completely healed within 4 weeks after surgery. Fistula healing was defined as the absence of any anal symptom, with no discharge from the fistula and a closed external opening confirmed on clinical evaluation. Fistula healing was eventually confirmed by a pelvic MRI at 3 months after surgery.Moreover, we analyzed postoperative pain measured by Visual Analogue Scale for 2 weeks after surgery to evaluate whether CAT injection could modulate pain, and recurrence at 6 months to evaluate the long-term efficacy of CAT injection. Faecal continence was assessed before surgery and at 6-months follow-up visit using the Cleveland Clinical Florida Fecal Incontinence (CCF-FI) questionnaire. Adipose tissue from periombelical or lateral abdomen was harvested from these patients by liposuction to prepare CAT using Coleman's technique.Complex anal fistulas were treated by conventional surgery. Once the seton (present in the most of patients) was removed, after identification of internal opening, necrotic and inflamed tissues were excised using a "cone-like" fistulectomy or debrided with a wire brush to remove granulation tissue by the help of fistuloscope (VAAFT modified, without destroying the fistulous track with monopolar electrode). Before CAT injection, the internal opening was treated in two ways: by simply closing it using 2-0 Vicryl stitches on the muscular and mucosal layers or by performing a mucosal advancement rectal flap. CAT was injected into the submucosal layer surrounding the internal opening, and around the fistula tract wall (in case of VAAFT modified) or inside the perianal wound after fistulectomy, using a 1-mL syringe equipped with a 22-gauge and 30-mm length needle, dividing injections at all quadrants of fistula wall, or distributing the CAT inside the perianal wound, at different levels by using multiple passes from the internal to the external openings until there was firm swelling surrounded the fistula tract. The external opening was approximated loosely with a suture to allow drainage of the fistula, but not extrusion of the centrifuged adipose tissue. The amount of product injected may vary depending on the total amount harvested but it should be not less than 10 ml. Patients were assessed for fistula healing, pain (VAS) and AEs at 1 week, 2 weeks, 4 weeks, 8 weeks, three months, and 6 months after treatment. Assessment consisted of clinical examination and AEs and VAS registration. Pelvic MRI was performed at 3 months after surgery. The Cleveland Clinical Florida Fecal Incontinence (CCF-FI) questionnaire was administered before surgery and at 6-months follow-up visit. At the final visit patients were also asked about their overall satisfaction with the procedure, with ratings from very satisfied to very dissatisfied.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anal Fistula
Keywords
complex fistula-in ano, adipose tissue, stem cell therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
This monocentric randomized controlled study was designed to test the efficacy and safety of injection of CAT for treatment of complex fistula-in ano, not associated with CD . Eligible patients were randomly assigned, according to a 1:1 scheme, to receive treatment with or without CAT. In the experimental arm, anal fistulas were treated by conventional surgery, and CAT injection. No experimental treatment (CAT) was administered to the control arm.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CAT injection group
Arm Type
Experimental
Arm Description
After fistulectomy for complex anal fistula, CAT (harvested from abdominal subcutaneous adipose tissue by Coleman's procedure) was injected into the tissue surrounding the internal opening, and inside the perianal wound obtained after fistulectomy.
Arm Title
No CAT injection group
Arm Type
No Intervention
Arm Description
Patients of this group were treated with anal fistulectomy without CAT injection.
Intervention Type
Procedure
Intervention Name(s)
Autologous centrifuged adipose tissue (CAT) injection after anal fistulectomy
Intervention Description
Collection and injection of autologous adipose tissue in complex anal fistulas in one surgical step under locoregional or general anesthesia.
Primary Outcome Measure Information:
Title
Fistula healing rate within 6 months after surgery
Description
Fistula healing was defined as the absence of any anal symptom, with no discharge from the fistula and a closed external opening confirmed on clinical evaluation. Fistula healing was eventually confirmed by a pelvic MRI at 3 months after surgery
Time Frame
up to 6 months
Secondary Outcome Measure Information:
Title
Safety of autologous adipose tissue injection
Description
Safety was evaluated by the overall incidence and severity of Adverse Events (AEs) up to 4 weeks following surgery.
Time Frame
4 weeks
Other Pre-specified Outcome Measures:
Title
postoperative pain
Description
postoperative pain measured by Visual Analogue Scale (0-10) for 2 weeks after surgery to evaluate whether CAT injection could modulate pain
Time Frame
2 weeks
Title
recurrence at 6 months
Description
to evaluate the long-term efficacy of CAT injection
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Patients aged 18 years or older with complex perianal fistulas Exclusion Criteria: Inflammatory bowel diseases, Crohn's Disease (CD) or Ulcerative Colitis (UC) Hepatitis B or C virus Infection with Human immunodeficiency virus Surgery for a malignant tumor during the previous 5 years (excluding in situ carcinoma) Previous pelvic radiotherapy Autoimmune disease Active tuberculosis Symptoms of septicemia Breastfeeding or pregnant women Women unwilling to use contraception during the study Psychiatric disorders Alcoholism Drug dependency Allergy to local anesthetics
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Simona Ascanelli, MD
Organizational Affiliation
University Hospital Ferrara
Official's Role
Principal Investigator
Facility Information:
Facility Name
Simona Ascanelli
City
Ferrara
ZIP/Postal Code
44121
Country
Italy

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified individual participant data for all primary and secondary outcome measures will be made available.
IPD Sharing Time Frame
Data will be available within 12 months of study completion
IPD Sharing Access Criteria
Data access requests will be reviewed by an external indipendent review Panel. Requestores will be required to sign a Data Access Agreement.
Citations:
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Citation
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derived

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Treatment of Complex Anal Fistulas Using Centrifuged Adipose Tissue Containing Progenitor Cells

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