Perianal FistulaPhase 3PISA-IINCT06441526
Surgical Closure vs Anti-TNF in the Treatment of Perianal Fistulas in Crohn's Disease (PISA-II): a Comprehensive Cohort Design
A Phase 3 study testing anti-tumour necrosis factor α antibodies and Advancement plasty in people with Perianal Fistula and Crohn Disease, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial summary
Currently, the treatment of Crohn's patients with perianal fistulas predominantly exists of anti-TNF medication. However, its efficiency has never been directly compared to surgical closure of the perianal fistula. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Perianal Fistula, Crohn Disease
- What is being tested?
- anti-tumour necrosis factor α antibodies and Advancement plasty
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 94 participants
- Where
- 1 siteNetherlands
- Study dates
- 14 Sep 2013to 7 Jun 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- ≥ 18 years
- (re-)active perianal fistula
- High perianal fistula tract (intersphincteric, transsphincteric, suprasphincteric) located in the upper two-thirds of the external sphincter or puborectal muscle
- Fistula with one internal opening (based on MRI imaging). The number of external fistulas does not have to be taken into account
- Written informed consent
- 4.3 Exclusion criteria
Show all 15Show fewer
- Proctitis (defined as any active mucosal inflammation or ulcer > 5mm in the rectum)
- Anorectal stenosis (defined as the impossibility to introduce a proctoscope)
- Submucosal fistulas \& low intersphincteric fistulas (lower one-third of external sphincter)
- Rectovaginal fistula
- Multiple internal openings
- Use of Anti-TNF medication for more than 3 months
- Previous failure of Anti-TNF treatment for perianal fistula
- Patients with a stoma
- Dementia or altered mental status that would prohibit the understanding and giving of informed consent
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Surgical Closure Versus Anti-TNF in the Treatment of Perianal Fistulas in Crohn's Disease (PISA-II): a Comprehensive Cohort Design
Currently, the treatment of Crohn's patients with perianal fistulas predominantly exists of anti-TNF medication. However, its efficiency has never been directly compared to surgical closure of the perianal fistula. The aim of this study is to compare radiological fistula healing at MRI after 18 months follow-up in Crohn's patients undergoing surgical closure to anti-TNF medication as treatment of perianal Crohn's fistulas.
Study design: In this multicenter comprehensive cohort design (CCD) Crohn's patients with a (re)active high perianal fistula will be allocated to anti-TNF for 1 year or surgical closure after 2 months under a short course of anti-TNF. Patients with a distinct preference will be treated accordingly, whereas only indifferent patients will be randomised in the usual way.
Read more
Main study parameters/endpoints: The primary outcome parameter is the number of patients with radiologically closed fistulas based on an evaluated MRI-score after 18 months. Secondary outcomes are clinical closure, number of patients undergoing surgical re-interventions and number of re-interventions, recurrences and quality of life based on the Perianal Disease Activity Index (PDAI).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: All patients will receive one of the two standard treatment approaches that are currently used for Crohn's fistulas. All effort has been performed to ensure most optimal treatment, according to best available evidence and current guidelines. Since there is no experimental study-arm, there are no additional risks associated with participation. During the study, the medical staff and trial nurses will monitor the necessity of surgical interventions and hospitalizations. At baseline and after 18 months all patients will undergo a MRI to score the fistula. Secondary outcome parameters will be assessed during visits to the outpatient clinic or telephone consultations at baseline and at intervals of 3 months for the duration of the study period. Every 6 months patients were asked to fill out the PDAI questionnaire with their physician. Based on the available literature, radiological closure of fistulas is expected in 40% of patients in the surgical closure group compared to 15% in the anti-TNF group. The increase in closure rate from 15% to 40% is considered clinically relevant. Due to the combination of a preference and randomized cohort, the appropriate sample size to detect this 25% difference is flexible and is adjusted for a skewed distribution. The minimal sample size, in case of a 1:1 treatment allocation, needed to detect this difference with a Chi-square test equals 86 patients (alpha 0.05, power 80%). The maximal allowed skewed distribution is set at 1:4, which will result in a maximal sample size of 116 patients.
- Conditions
- Perianal Fistula, Crohn Disease
- Being tested
- anti-tumour necrosis factor α antibodies, Advancement plasty
- Keywords
- Crohn's disease, Perianal fistula, Anti-TNF, Advancement plasty, LIFT-procedure, Fistula closure, Comprehensive cohort design
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-tumour necrosis factor α antibodiesDrug
Biological drug
Advancement plastyProcedure or surgery
Also called Ligation of the intersphincteric tract (LIFT)
Surgical closure of the internal opening
| Study group | Role | What they receive |
|---|---|---|
| Anti-TNF | Active comparator | Seton placement, followed by anti-TNF medication (infliximab or adalimumab) in combination with a immunomodulator after ± 2 weeks. The seton will be removed after ± 6 weeks. Continuation of anti-TNF medication for at least 1 year, after one year continuation is at the discretion of treating physician. Receives: Drug: anti-tumour necrosis factor α antibodies |
| Surgical closure | Active comparator | Seton placement, followed by anti-TNF medication in combination with a immunomodulator after ± 2 weeks. After 8-10 weeks removal of seton and surgical closure (advancement plasty or ligation of the intersphincteric tract (LIFT) procedure). Anti-TNF in combination with a immunomodulator will be stopped after ± 4 months. Receives: Procedure: Advancement plasty |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fistula closure
The number of patients with radiologically closed (completely fibrotic) fistula tract on MRI
Measured: at 1,5 year
Secondary outcomes (5)
Clinical closure
The number of patients with clinical closure, defined as closure of the external opening without discharge of pus or faeces on palpation
Measured: at 1,5 year
The number of patients undergoing surgical re-intervention
Amount of patients undergoing surgical re-intervention
Measured: at 1,5 year
The number of re-intervention
Amount of re-interventions
Measured: at 1,5 year
The quality of life of a patient
measured by the Perianal Disease Activity Index (PDAI score)
Measured: Every six months from baseline till 18 months
The number of recurrences
Amount of patients with a recurrence, defined as re-opening of the external opening after clinical closure
Measured: at 1,5 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2024
- Study start14 Sep 2013
- Primary completion7 Dec 2019
- Study completion7 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Perianal FistulaStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is an international, multicentre, prospective, comprehensive cohort design trial to identify the most optimal treatment of Crohn's high perianal fistulas. In a comprehensive cohort design patients with a preference will be treated accordingly, whereas only those indifferent to treatment will be randomised in the usual way (combined randomised and preference cohort).
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 94 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Willem A. Bemelman, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- Willem Bemelman, MD PhD, Principal investigator, Amsterdam UMC, location AMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06441526
- Sponsor's protocol ID
- NL66176.018.18
- Acronym
- PISA-II
- Status last verified
- Jun 2024
- First submitted
- 10 Apr 2019
- Last updated
- 4 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Surgical Closure Versus Anti-TNF in the Treatment of Perianal Fistulas in Crohn's Disease (PISA-II): a Comprehensive Cohort Design
- ClinicalTrials.gov ID
- NCT06441526
- Acronym / sponsor ID
- PISA-II / NL66176.018.18
- Conditions
- Perianal Fistula, Crohn Disease
- Keywords
- Crohn's disease, Perianal fistula, Anti-TNF, Advancement plasty, LIFT-procedure, Fistula closure, Comprehensive cohort design
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 94 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Study start
- 14 Sep 2013 (actual)
- Primary completion
- 7 Dec 2019 (actual)
- Study completion
- 7 Jun 2021 (actual)
- First posted
- 4 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Currently, the treatment of Crohn's patients with perianal fistulas predominantly exists of anti-TNF medication. However, its efficiency has never been directly compared to surgical closure of the perianal fistula. The aim of this study is to compare radiological fistula healing at MRI after 18 months follow-up in Crohn's patients undergoing surgical closure to anti-TNF medication as treatment of perianal Crohn's fistulas.
Study design: In this multicenter comprehensive cohort design (CCD) Crohn's patients with a (re)active high perianal fistula will be allocated to anti-TNF for 1 year or surgical closure after 2 months under a short course of anti-TNF. Patients with a distinct preference will be treated accordingly, whereas only indifferent patients will be randomised in the usual way.
Main study parameters/endpoints: The primary outcome parameter is the number of patients with radiologically closed fistulas based on an evaluated MRI-score after 18 months. Secondary outcomes are clinical closure, number of patients undergoing surgical re-interventions and number of re-interventions, recurrences and quality of life based on the Perianal Disease Activity Index (PDAI).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: All patients will receive one of the two standard treatment approaches that are currently used for Crohn's fistulas. All effort has been performed to ensure most optimal treatment, according to best available evidence and current guidelines. Since there is no experimental study-arm, there are no additional risks associated with participation. During the study, the medical staff and trial nurses will monitor the necessity of surgical interventions and hospitalizations. At baseline and after 18 months all patients will undergo a MRI to score the fistula. Secondary outcome parameters will be assessed during visits to the outpatient clinic or telephone consultations at baseline and at intervals of 3 months for the duration of the study period. Every 6 months patients were asked to fill out the PDAI questionnaire with their physician. Based on the available literature, radiological closure of fistulas is expected in 40% of patients in the surgical closure group compared to 15% in the anti-TNF group. The increase in closure rate from 15% to 40% is considered clinically relevant. Due to the combination of a preference and randomized cohort, the appropriate sample size to detect this 25% difference is flexible and is adjusted for a skewed distribution. The minimal sample size, in case of a 1:1 treatment allocation, needed to detect this difference with a Chi-square test equals 86 patients (alpha 0.05, power 80%). The maximal allowed skewed distribution is set at 1:4, which will result in a maximal sample size of 116 patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- This is an international, multicentre, prospective, comprehensive cohort design trial to identify the most optimal treatment of Crohn's high perianal fistulas. In a comprehensive cohort design patients with a preference will be treated accordingly, whereas only those indifferent to treatment will be randomised in the usual way (combined randomised and preference cohort).
| Arm | Type | Receives |
|---|---|---|
| Anti-TNF | Active comparator | Drug: anti-tumour necrosis factor α antibodiesSeton placement, followed by anti-TNF medication (infliximab or adalimumab) in combination with a immunomodulator after ± 2 weeks. The seton will be removed after ± 6 weeks. Continuation of anti-TNF medication for at least 1 year, after one year continuation is at the discretion of treating physician. |
| Surgical closure | Active comparator | Procedure: Advancement plastySeton placement, followed by anti-TNF medication in combination with a immunomodulator after ± 2 weeks. After 8-10 weeks removal of seton and surgical closure (advancement plasty or ligation of the intersphincteric tract (LIFT) procedure). Anti-TNF in combination with a immunomodulator will be stopped after ± 4 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- ≥ 18 years
- (re-)active perianal fistula
- High perianal fistula tract (intersphincteric, transsphincteric, suprasphincteric) located in the upper two-thirds of the external sphincter or puborectal muscle
- Fistula with one internal opening (based on MRI imaging). The number of external fistulas does not have to be taken into account
- Written informed consent
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| anti-tumour necrosis factor α antibodiesBiological drug | Drug | Anti-TNF |
| Advancement plastyAlso: Ligation of the intersphincteric tract (LIFT)Surgical closure of the internal opening | Procedure or surgery | Surgical closure |
Primary outcome
Fistula closure
Time frame: at 1,5 year
The number of patients with radiologically closed (completely fibrotic) fistula tract on MRI
5 secondary outcomes
Clinical closure
Time frame: at 1,5 year
The number of patients undergoing surgical re-intervention
Time frame: at 1,5 year
The number of re-intervention
Time frame: at 1,5 year
The quality of life of a patient
Time frame: Every six months from baseline till 18 months
The number of recurrences
Time frame: at 1,5 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2024.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Willem Bemelman, MD PhD principal investigator
Amsterdam UMC, location AMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing anti-tumour necrosis factor α antibodies and Advancement plasty in people with Perianal Fistula and Crohn Disease, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fistula closure (time frame: at 1,5 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2024.