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Trial registered on ANZCTR


Registration number
ACTRN12616001258448
Ethics application status
Approved
Date submitted
26/07/2016
Date registered
8/09/2016
Date last updated
31/10/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Randomised controlled trial comparing cutting seton vs ligation of intersphincteric fistula tract (LIFT) for complex anal fistula
Scientific title
Randomised control trial comparing clinical outcome of adult patients with anal fistulae treated with cutting seton or LIFT procedure
Secondary ID [1] 286947 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anal fistulae 295385 0
Condition category
Condition code
Surgery 295648 295648 0 0
Surgical techniques
Oral and Gastrointestinal 299756 299756 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention : Cutting seton
Cutting seton will be placed through the fistula track with the aid of Lockhart-Mummery. The anoderm overlying the sphincter complex will be scored with diathermy and the vessel loop secured snugly with suture ties. This duration of this procedure is approximately 45 minutes and will be performed by consultant colorectal surgeon. Patients will be reviewed every 6 weeks, and readmitted for tightening of the seton at a minimum of 6 weekly intervals until completion of treatment.
Completion of treatment is when the seton has cut through the sphincter . This decision is made by the treating Surgeon.
Intervention code [1] 292142 0
Treatment: Surgery
Comparator / control treatment
Comparator treatment: LIFT procedure
An incision is performed in the intersphincteric groove. The primary fistula tract is dissected out and isolated. The track is ligated and where possible, a section excised for histopathology. Where possible, the external track lateral to the sphincter complex is either excised or curetted. The duration of this procedure is approximateley 45 minutes and will be performed by consultant colorectal surgeon.
Control group
Active

Outcomes
Primary outcome [1] 298924 0
Primary healing rate: defined as complete healing of the fistula track and external opening.
Timepoint [1] 298924 0
12 weeks post surgery
Secondary outcome [1] 326517 0
Secondary healing rate: defined as healing after second line therapy.
Timepoint [1] 326517 0
12 months post second line therapy
Secondary outcome [2] 326518 0
Recurrence: defined as any new onset of symptoms and an external fistula opening after documented complete healing identified by consultant colorectal surgeon.
Timepoint [2] 326518 0
6 months and 12 months post therapy
Secondary outcome [3] 326519 0
Continence: this will be assessed using the St Mark’s continence severity score.
Timepoint [3] 326519 0
6weeks, 12weeks, 18weeks, 6 months and 12 months post therapy
Secondary outcome [4] 326520 0
Anorectal physiology measures: anal manometry measured by stationery water perfused catheter. Endoanal ultrasound using B&K 3000 3d rotating anal transducer.
Timepoint [4] 326520 0
pre operatively and 12 weeks post healing
Secondary outcome [5] 326523 0
Time to primary healing: defined as complete healing of the fistula track and external opening.
Timepoint [5] 326523 0
6 weeks, 12 weeks, 18 weeks, 6 months, 12 months post operative
Secondary outcome [6] 326524 0
Pain as measured on a visual analogue scale.
Timepoint [6] 326524 0
6 weeks, 12 weeks, 18 weeks 6 months and 12 months postoperative
Secondary outcome [7] 326526 0
Stoma requirement as a result of treatment failure. This will be assessed by review of medical records.
Timepoint [7] 326526 0
12 months post operative
Secondary outcome [8] 326527 0
Patient satisfaction measured on a visual analogue scale
Timepoint [8] 326527 0
6weeks, 12 weeks, 18weeks, 6 months and 12 months.
Secondary outcome [9] 326529 0
Patient quality of life measured by questionnaire SF -12
Timepoint [9] 326529 0
Preoperatively and 12 months.

Eligibility
Key inclusion criteria
Adult patients aged 18-80 years with complex anal fistula. Complex fistulae are defined as high trans-sphincteric or supra-sphincteric fistulae, anteriorly situated fistulae in women, fistula disease in the presence of impaired continence, and any recurrent fistula.
Current loose seton in situ for drainage of sepsis
Able to give valid consent
Deemed suitable for either LIFT or cutting seton procedure by treating surgeon
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Current active inflammatory bowel disease or known history of inflammatory bowel disease.
Fistulae not of cryptoglandular aetiology (e.g. radiation, foreign body, iatrogenic)
Multiple medical co-morbidities
Deemed unsuitable by the treating surgeon for either cutting seton or LIFT procedure

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
There will be no allocation concealment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation will be computer generated. Entrance into the randomisation will be preceded by stratification according to gender ( male or female) and previous anal fistula (yes or no).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Consecutive patients will be allocated to either LIFT or cutting seton by computer generated randomisation. Prior to randomisation, participants will be stratified according to gender and previous fistula procedures yes or no. Randomisation will be administered by an independent person.
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Primary analysis will be at 3 months and longitudinal analysis will be 6 and 12 months and take into account secondary outcomes and correlated to patients. Repeated measures will be analysed using ANOVA with mixed modeling principles. Effects ( fixed and random) will be specified and estimated to identify which mechanisms and the degree to which they affected outcomes.
Descriptive analysis will be used to calculate mean, median and report 95% confidence intervals. Differences in continuous normally distributed data will be calculated using a t test. Differences in categorical variable will be calculated using Mann Whitney U test and Wilcoxin sign ranks test. Multivariate and univariate analysis will be performed and significance will be set at 0.05.
From current literature, the median rate of primary healing is 71% and 98.5% for LIFT and cutting seton, respectively. Using Pocock’s formula comparing two proportions in a randomised clinical trial with a difference of 20%, significance of 0.05 and rate of 30%, the number of patients in each group is determined to be 93. Allowing for dropouts, the total number to be recruited into the study will be 200 patients.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 6155 0
St George Hospital - Kogarah
Recruitment hospital [2] 6156 0
Prince of Wales Private Hospital - Randwick
Recruitment postcode(s) [1] 13595 0
2217 - Kogarah
Recruitment postcode(s) [2] 13698 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 294259 0
Hospital
Name [1] 294259 0
St George Hospital
Address [1] 294259 0
Gray Street
KOGARAH NSW 2217
Country [1] 294259 0
Australia
Primary sponsor type
Hospital
Name
St George Hospital Colorectal research fund
Address
Pelvic Floor Unit
Gray Street
Kogarah NSW 2217
Country
Australia
Secondary sponsor category [1] 293090 0
None
Name [1] 293090 0
None
Address [1] 293090 0
None
Country [1] 293090 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295463 0
SESLHD Human Research Ethics Committee
Ethics committee address [1] 295463 0
South Eastern Sydney Local Health District
Prince of Wales Hospital
G71 East Wing, Edmund Blacket Building
Cnr High & Avoca Streets
Randwick NSW 2031
Ethics committee country [1] 295463 0
Australia
Date submitted for ethics approval [1] 295463 0
29/09/2015
Approval date [1] 295463 0
26/07/2016
Ethics approval number [1] 295463 0
15/2389HREC/15/POWH/446

Summary
Brief summary
Anal fistula is a common condition. The aims of treatment are fistula healing, prevention of recurrence and maintenance of continence. Treatment options and their associated risks vary according to the fistula track. Simple fistulae (intersphincteric or low trans-sphincteric) may be treated successfully with fistulotomy. Complex fistulae pose a therapeutic challenge and carry a higher risk of treatment failure, altered continence and recurrence. (Joy and Williams 2002) (van okelen, Gosselink et al. 2013) To date, no single intervention simultaneously fulfils all three therapeutic aims.

The cutting seton has been employed for centuries and involves the use of various materials (including suture, vessel loops etc) to slowly divide through the sphincter and induce fibrosis. The literature reports recurrence rates in the 3 – 5 % range (Vial, Pares et al. 2010) . Reported incontinence rates after cutting seton vary widely from 0 - 63 % (Vial, Pares et al. 2010) (Garcia-Aguilar, Belmonte et al. 1998) (Karri-Pekka, Hamalainen et al. 1997) (Charua-Guindic, Mendez-Moran et al. 2007) (Ritchie, Sackier et al. 2008) , which may be partially attributable to incomplete/inadequate scarring behind the seton when tightened rapidly.

The ligation of the intersphincteric track (LIFT) procedure was described in 2007 as a sphincter preserving technique for high fistulae. (Rojanasakul, Pattanaarun et al. 2007) Early reports published fistula cure and continence rates in excess of 90% (ref). Subsequent series have reported success rates ranging from 57% to 82%. (Yassin, Hammond et al. 2013) The procedure involves identification, dissection and then ligation of the fistula track in the intersphincteric space, thereby eliminating the fistula source from its track and avoiding the need for sphincter division.

Multiple interventions to manage fistulae have been described including sphincter preserving techniques such as fibrin plugs and tissue glue. (Ellis and Clark 2006) (Garg 2009) With the prospect of altered continence as a complication, heterogeneity of fistula anatomy, and the interplay with physiology, studies are limited in their ability to generalise findings and recommend treatments in the form of guidelines.

Aim
To prospectively assess the clinical outcomes of patients with complex fistulae treated by cutting seton and compare these to patients treated by LIFT.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 58226 0
Dr Kim Chi Phan Thien
Address 58226 0
Sydney Colorectal Assc
37 Gloucester Rd
Hurstville NSW 2220
Country 58226 0
Australia
Phone 58226 0
+61 2 85661000
Fax 58226 0
+61 2 91133546
Email 58226 0
kimchiphanthien@sydneycolorectal.com.au
Contact person for public queries
Name 58227 0
Mrs Vicki Patton
Address 58227 0
Pelvic Floor Unit
St George Hospital
Gray Street
KOGARAH NSW 2217
Country 58227 0
Australia
Phone 58227 0
+61 2 91132715
Fax 58227 0
+61 2 9113 3546
Email 58227 0
vicki.patton@health.nsw.gov.au
Contact person for scientific queries
Name 58228 0
Dr Kim Chi Phan Thien
Address 58228 0
Sydney Colorectal Assc
37 Gloucester Rd
Hurstville NSW 2220
Country 58228 0
Australia
Phone 58228 0
+61285661000
Fax 58228 0
+61 2 9113 3546
Email 58228 0
kimchiphanthien@sydneycolorectal.com.au

No information has been provided regarding IPD availability
Summary results
No Results