Semiflex assisted vacuum therapy for perianal abscesses/sinuses and fistula: a pilot study

Perianal fistulas are a common, invalidating problem with an estimated
incidence of 1.2-2.8 per 10 000 people in Europe.1 Over 90% of the perianal
fistulas originate from cryptoglandular sepsis, whereas around 26% of patients
with Crohn*s disease will develop one or more perianal fistulas within 20 years
after diagnosis.2,3 Treatment of perianal fistulas depends on the underlying
pathology, presence of perianal abscesses, the involvement of the external
sphincter complex and the fistula characteristics such as the number of
internal openings and fistula tracts. Low perianal fistulas crossing less than
the lower one-third of the external anal sphincter are easily and mostly
successfully treated by fistulotomy. High perianal fistulas are more difficult
to eradicate due to a serious risk of sphincter and perianal tissue
destruction. Treatment of high perianal fistulas in Crohn*s disease is even
more challenging with an increased risk of continence impairment due to the
presence of diarrhoea throughout the patient*s life. Permanent closure of
fistulas in patients with Crohn*s disease requires a multidisciplinary approach
of combining medical therapy with surgery. Not rarely, multiple surgeries are
necessary, especially when septic cavities are present.

In order to prevent recurrent abscess formation treatment of perianal fistulas
usually starts with the insertion of a non-cutting seton.4 After appropriate
drainage, an attempt at clinical closure can be made in selected fistula which
consist mainly of the endorectal advancement flap procedure and the ligation of
the intersphincteric fistula tract (LIFT) procedure. However, surgical attempts
to close the fistula are technically more difficult in case of multiple
internal openings. Overall success rates are reported up to 70% after these
procedures for single fistula tracts, but with recurrences in around 22%.5
Thus, a more effective and widely applicable alternative treatment is necessary.

In addition, several conditions exist where there is a large sinus in the
pelvis, perianal or after proctectomy. These conditions are very difficult to
manage with passive drains and often require major surgery with placement of
vital tissue in the tracts. These sinuses or abscesses might benefit from
vacuum therapy. Vacuum therapy has become one of the main pillars for
management of a wide variety of (chronic) wound healing problems. Vacuum
Assisted Closure (VAC) treatment promotes wound healing by reducing tissue
oedema, increasing blood flow and by accelerating formation of a granulation
tissue, and is therefore widely used for (surgical) wounds.6 After closure of
the internal opening, the fistula tract is treated with vacuum therapy. To
date, only one cohort study by Hermann et al.7 was published on VAC of perianal
fistulas, which showed promising clinical closure rates of 75% using homemade
vacuum catheters. The difficulty with the currently available homemade vacuum
catheters is that they need to be exchanged under anaesthesia.

A 3D designed and Silicone printed vacuum catheter was developed to enable
vacuum therapy in the outpatient setting and exchange of the catheter system
without the need of anaesthesia. The presented pilot study tried to determine
the feasibility and applicability of the Semiflex catheters.

1. Zanotti C, Martinez-Puente C, Pascual I, Pascual M, Herreros D, García-Olmo
D. An assessment of the incidence of fistula-in-ano in four countries of the
European Union. Int J Colorectal Dis. 2007;22(12):1459-62.

2. Parks AG. Pathogenesis and treatment of fistuila-in-ano. Br Med J.
1961;1(5224):463-9.

3. Schwartz DA, Loftus EV, Jr., Tremaine WJ, Panaccione R, Harmsen WS,
Zinsmeister AR, et al. The natural history of fistulizing Crohn's disease in
Olmsted County, Minnesota. Gastroenterology. 2002;122(4):875-80.

4. Magro F, Gionchetti P, Eliakim R, Ardizzone S, Armuzzi A, Barreiro-de Acosta
M, et al. Third European Evidence-based Consensus on Diagnosis and Management
of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal
Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch
Disorders. J Crohns Colitis. 2017;11(6):649-70.

5. Stellingwerf ME, van Praag EM, Tozer PJ, Bemelman WA, Buskens CJ.
Systematic review and meta-analysis of endorectal advancement flap and ligation
of the intersphincteric fistula tract for cryptoglandular and Crohn's high
perianal fistulas. BJS Open. 2019;3(3):231-41.

6. Poteet SJ, Schulz SA, Povoski SP, Chao AH. Negative pressure wound therapy:
device design, indications, and the evidence supporting its use. Expert Rev Med
Devices. 2021;18(2):151-60.

7. Hermann J, Banasiewicz T, Ko*odziejczak B. Role of Vacuum-Assisted Closure
in the Management of Crohn Anal Fistulas. Adv Skin Wound Care.
2019;32(1):35-40.

With this pilot study we aim to determine the feasibility and efficacy of the
novel catheter set, the Semiflex Dome Catheter System, for vacuum therapy of
perianal abscesses/sinuses and fistulas. The pilot study will consist of 2
parts. First, 10 patients in each study group will be included in the study.
After inclusion of these 20 patients, it will be assessed per study group
whether the catheter meets the proof of principle. This assessment will be done
by the DSMB. After a positive result in one or both study groups, the second
part of the study will start. 10 patients in each study group will be included
in five different hospitals. In total 40 patients will be included.

Objectives study part 1: Pilot in the Amsterdam UMC
Primary Objective:
The primary objective of the first part of the pilot study is to determine if
the Semiflex Dome Catheter System meets the proof of principle with respect to:
a. Smoothness of insertion and changing the semiflex catheters
• Is it feasible to insert the catheter?
• How painful is the changing of the catheters based on the Visual Analoge
Score (VAS)? A VAS >5 is considered too painful.
b. Capability of proper fixation of the catheter
• Will the catheter be fixed during the study period?
c. Capability of maintaining vacuum for more than 48 hours
• Will the vacuum be maintained for more than 48 hours?
d. Compliance to the therapy in terms of pain and discomfort
• How uncomfortable/ painful is the catheter for the patient based on the VAS?
A VAS >5 is considered too painful.

The proof of principle will be met when 50% of the participants per study group
meet all the primary objectives, so point A,B,C and D. These points will be
scored individually and only if one individual meets all of the points, the
participant will be scored as successful. If 50% or more of the participants
per study group are successful, the proof of principle in that corresponding
study group is met. This correspondence with a minimum of 5 participants per
study group. When the fistula group and/ or the perianal abscess/sinus group
meets the proof of principle, the second part of the pilot study will start. A
percentage of 50% has been chosen, so the procedure can be optimized at the
Amsterdam UMC, taking a learning curve into account.


Objectives study part 2: Participation other centers
Primary Objective:
The primary objective of the second part of the pilot study is to determine
feasibility of the Semiflex Dome Catheter System with respect to:
a. Smoothness of insertion and changing the semiflex catheters
• Is it feasible to insert the catheter?
• How painful is the changing of the catheters based on the Visual Analoge
Score (VAS)? A VAS >5 is considered too painful.
b. Capability of proper fixation of the catheter
• Will the catheter be fixed during the study period?
c. Capability of maintaining vacuum for more than 48 hours
• Will the vacuum be maintained for more than 48 hours?
d. Compliance to the therapy in terms of pain and discomfort
• How uncomfortable/ painful is the catheter for the patient based on the VAS?
A VAS >5 is considered too painful.

The proposed treatment protocol is considered feasible if at least 70% of the
participants per study group meet all the primary objectives. This means that
point A, B, C, and D of the primary objectives are met in each individual
participant. This correspondence with 7 participants per study group.

Secondary Objectives:
Secondary objectives of this study are:
a. Efficacy of drainage of perianal abscess/sinus (e.g. absence of retention)
b. Efficacy of curing the perianal abscess/sinus in terms of complete collapse
of the sinus and disappearance of induration
c. Efficacy of management of perianal fistula in terms of healing after
successive exchanges (first placement is in combination with closure of the
internal opening)
d. Radiological healing defined as complete fibrosis on magnetic resonance
imaging (MRI)
e. Safety of the Semiflex Dome Catheter System in terms of complications which
may occur during treatment

The design of the pilot study is a feasibility study with insertion of Semiflex
catheters in patients with a perianal abscess/sinus and fistulas. The pilot
study will consist of 2 parts. First, 10 patients in each study group
fulfilling the inclusion criteria without any exclusion criteria will be
included in the study. This first part of the study will be conducted in the
AUMC. After inclusion of these 20 patients, it will be assessed per study group
whether the catheter meets the proof of principle. This assessment will be done
by the DSMB.
After a positive result in one or both study groups, the second part of the
pilot study will start. The second part of the pilot study will be conducted in
the Amsterdam UMC, Pozna* University of Medical Sciences, the San Raffaele
University Hospital, the Maastricht University Medical Center, the
Proctosclinic, and University Hospital Leuven. Patients fulfilling the
inclusion criteria without any exclusion criteria will be included in the
study. In this second part 10 patients per study group will be included. In
total, 40 patients will be included and inclusion is scheduled to take place
within 6 months.
Patients will be seen at the outpatient clinic 2-3 days after insertion of the
semiflex catheter
by the surgeon where it will be replaced by a smaller sized Semiflex dome
catheter. This will be continued until the fistula or perianal abscess/sinus is
closed. The therapy is continued for approximately 4 weeks in patients with a
perianal fistula and approximately 6 weeks in patients with perianal
abscess/sinus, depending on the length of the fistula tract or abscess/sinus.
During these contacts outcome parameters will be assessed. Patients will be
contacted by telephone after ± 2 weeks and 3 months by the study coordinator to
assess complications, additional interventions, re-admissions, duration of
hospital stay and visits to the outpatient clinic. After 3 months a MRI will be
made to assess the healing of the perianal abscess/sinus and clinical closure
of the perianal fistula.
When the results of the study are positive, a conformity study will be
started.

Patients with a perianal abscess/sinus or (Crohn*s) perianal fistula will be
included in the study. This study will evaluate two groups of patients. The
first group will consist of patients presenting with a perianal abscess/sinus
and the other group will consist of patients with the presence of a (Crohn*s)
perianal fistula.

Patients with a perianal abscess/sinus
In patients that present with a perianal abscess/sinus the semiflex dome
catheter is inserted under general anesthesia. A small cut is made to drain and
irrigate the septic sinus, unless an opening is already present. Before
surgery, the size of the perianal abscess/sinus is measured on MRI or CT. If
during surgery appears that this is not the appropriate size, a different size
catheter can be used. 29 sizes of the Semiflex catheters are available. The
Semiflex dome catheter is inserted with its plate fixed on Renasys Adhesive gel
patch (Smith and Nephew). The catheter is connected with a tubing system to a
vacuum pomp with an average vacuum pressure of 80 cm H2O. The tube will be
taped on the patient. The Semiflex stays in place and will be replaced after
every two- three days by a smaller sized Semiflex dome catheter as determined
during the outpatient visit. The exchange is meant to be done in the outpatient
setting after the administration of 50 mg of parenteral morphine if necessary.
The therapy is continued for approximately 6 weeks depending on the length of
the abscess/sinus.

Patients with perianal fistula
All patients that will be treated for their perianal fistula have had a seton
inserted for at least 6 weeks. Under general anesthesia the seton is removed,
the internal opening is excised (de-epithelialized) and the internal opening is
closed with a 2-0 Vicryl cross stitch.
Before surgery, the length of the tract is measured on MRI or CT. A Semiflex
Catheter with the appropriate length and a diameter between 3.0 and 5.1mm is
selected. If during surgery appears that this is not the appropriate size, a
different size catheter can be used. 29 sizes of the Semiflex catheters are
available. The catheter is fixed on a Renasys Adhesive gel patch (Smith and
Nephew). The catheter is connected with a tubing system to a vacuum pomp with
an average vacuum pressure of 80 cm H2O. The tube will be taped on the patient.
After every two - three days the catheter will be exchanged by a 3-6 mm shorter
catheter. The exchange is meant to be done in the outpatient setting after the
administration of 50 mg of parenteral morphine if necessary. The therapy is
continued for approximately 4 weeks depending on the length of the fistula
tract.

The Semiflex Dome Catheter may cause the following side effects, adverse
effects or discomfort:
- Tissue damage during insertion of the catheter or due to a 'foreign body'
reaction against the catheter. However, the chance of this is very low, because
the catheter is made entirely of medical grade silicone that has been used in
surgery for several decades. The ISO 10933 set includes a set of standards for
evaluating medical devices for safe use in humans. One of these ISO standards
that applies to the Semiflex catheter is ISO 10993-11. This ISO standard tests
the systemic toxicity of a medical device. This ISO standard has not yet been
released for the Semiflex Catheter because the production method, namely via
the 3D printer, is a new technique. However, tests have been done on the
Semiflex Catheter which show it to be non-toxic. The lack of ISO 10993-11
certification is therefore not seen as a risk.
- Tissue damage due to too high vacuum. However, the risk of this is very small
if patients adhere to the instructions for use of the vacuum pump. The doctor
will set the desired vacuum height per contact moment.
- Tissue damage due to the catheter being suddenly pulled out or breaking off.
The chance of this is minimized by taping the catheter tube to the patient's
body during treatment. If the catheter breaks off, there is a chance that it
will have to be removed in the operating room under anesthesia. Should the
catheter fall out or break off, patients should immediately contact the
principal investigator. If this is not available, patients should contact the
Amsterdam UMC, location AMC and ask for the surgeon on duty.
- Discomfort of wearing the catheter. The therapy is continued for
approximately 4 weeks in patients with a perianal fistula and approximately 6
weeks in patients with perianal abscess/sinus, depending on the length of the
fistula tract or abscess/sinus. This means that patients are treated with a
catheter connected to a portable vacuum pump during this period. It can be
experienced as a considerable burden to have to carry the vacuum pump with you
all the time. In addition, patients have to come to the outpatient clinic every
2-3 days to replace the catheter, which can be experienced as a considerable
burden.
- The Semiflex Dome Catheter does not work properly and patients develop
another abscess or the fistula continues to drain. Patients should immediately
contact the Principal Investigator if fever and/or suspected new abscess
occurs. If this is not available, patients should contact the Amsterdam UMC,
location AMC and ask for the surgeon on duty.