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Trial registered on ANZCTR


Registration number
ACTRN12613000254796
Ethics application status
Approved
Date submitted
28/02/2013
Date registered
4/03/2013
Date last updated
4/03/2013
Type of registration
Retrospectively registered

Titles & IDs
Public title
Botulinum toxin versus botulinum toxin with low dose Glyceryltrinitrite (GTN) cream for healing of chronic anal fissure: prospective, randomised trial
Scientific title
Botulinum toxin versus botulinum toxin with low dose Glyceryltrinitrite (GTN) cream for healing of chronic anal fissure: prospective, randomised trial
Secondary ID [1] 282039 0
nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic anal fissure 288494 0
Condition category
Condition code
Oral and Gastrointestinal 288842 288842 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
Botox-A injection 20 units in total, 10 units intramuscular to each side of internal anal sphincter at 3 and 9 o`clock position and 1cm of 0.2% GTN cream applied topically to anal fissure area for 6 weeks thrice daily.
Intervention code [1] 286629 0
Treatment: Drugs
Comparator / control treatment
Botox-A injection 20 units to Internal anal sphincter
Control group
Active

Outcomes
Primary outcome [1] 288970 0
Healing of anal fissure by direct visualization of fissure area using anal fissure grades.
Timepoint [1] 288970 0
12 weeks
Secondary outcome [1] 301471 0
Head aches with GTN by using numeric pain scale with range from 0-10.
Timepoint [1] 301471 0
6 weeks.

Eligibility
Key inclusion criteria
All patients with chronic anal fissure(CAF) from the Waikato region of New Zealand, with ages ranging from 18-80 years.
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
previous surgical treatment for anal fissure, pregnancy (current or planned) & lactation, inflammatory bowel disease, rectal or anal malignancy, unable to self administer medications, unable to complete necessary trial documentation or unable to attend necessary clinical follow up, any history of unexplained syncope or orthostatic hypotension, history of faecal incontinence, tuberculosis, HIV/AIDS, syphilis, peri-anal sepsis or fistulas, immunosuppressant and use of Viagra or other nitrate preparations for IHD

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)
Patients presenting after referral from GP to Anal fissure clinic in Waikato Hospital were assessed for their suitability for trial and then informed consent was obtained. Patients were allocated to group A (control) to receive 20 units of Botox injection only to internal anal sphincter and group B (exposure) to recieve 20 units of Botox injection and were prescribed with 0.2% GTN cream to apply 1cm of cream with glove to fissure area for 6 weeks.
Randomisation codes were generated by computer with study number from 1-50 before study started and patients were recruited to trial as they come in serial manner. There was no concealment in this study by means of third person.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Logistic regression for headache or not as the outcome and headache scores at baseline and group as explanatory variables.
Generalised linear mixed model to compare fissure pain score in two groups.

Recruitment
Recruitment status
Completed
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 outside Australia
Country [1] 4887 0
New Zealand
State/province [1] 4887 0
Waikato

Funding & Sponsors
Funding source category [1] 286817 0
Self funded/Unfunded
Name [1] 286817 0
Address [1] 286817 0
Country [1] 286817 0
New Zealand
Primary sponsor type
Hospital
Name
Waikato District Health Board
Address
Waikato Hospital, Pembroke street, Hamilton, Waikato 3204.
New Zealand.
Country
New Zealand
Secondary sponsor category [1] 285605 0
None
Name [1] 285605 0
Address [1] 285605 0
Country [1] 285605 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288883 0
Northern-Y Regional Ethics Committee
Ethics committee address [1] 288883 0
3rd Floor BNZ building, 354 Victoria street, Hamilton. 3204
Ethics committee country [1] 288883 0
New Zealand
Date submitted for ethics approval [1] 288883 0
01/09/2009
Approval date [1] 288883 0
27/11/2009
Ethics approval number [1] 288883 0
NTY/09/04/032

Summary
Brief summary
Anal fissure is one of the most common benign anorectal conditions, which may result from high internal anal sphincter (IAS) pressure. The goals of therapy are to break the cycle of sphincter spasm and tearing of anal mucosa, and to promote healing of fissure. Medical therapy is successful in the majority of patients with surgery reserved for refractory cases. Acute anal fissure usually heals spontaneously or with conservative treatment within six weeks, whereas chronic anal fissure is more intractable and is unlikely to heal with conventional conservative management.

Surgery by means of lateral internal sphincterotomy (LIS) carries the risk of permanent faecal incontinence. The risk has varied among reports from as low as 0 to as high as 24 percent. In Vitro and in vivo studies in animals have established that nitric oxide (NO) is probably the most important inhibitory neurotransmitter in IAS. Glyceryl trinitrite cream applied locally to the anus has been shown to cause lowering of IAS pressure in healthy subjects and to promote healing of anal fissures. Another non surgical agent for treatment for anal fissure is botulinum toxin (BT) which decreases the anal pressure by preventing release of acetylcholine from presynaptic nerve terminals. Maria et al reported a 73% healing rate for anal fissure after BT injection alone.

There is only one study previously, by Lysy et al., looking at the synergistic effect of BT and topical nitrates (isosorbide dinitrate) for healing of anal fissure, which showed significantly higher healing, 66%, in the combined treatment group compared to BT alone, 20%. Scholefield et al. conducted a dose finding study with different strengths of GTN for chronic anal fissure and found that 0.1% GTN cream has a higher healing rate compared to 0.2% cream, with a smaller percentage of patients reporting headaches: 18% versus 36% with 0.2% GTN cream.

The aims of the present study were to assess the efficacy, safety and patient compliance related to BT injection and combined treatment with BT injection and lowered dose 0.2% Glycerlytrinitite (GTN) cream for the treatment of CAF. We hypothesised that combined treatment would have a synergistic effect on healing and lowered dose GTN would help with patient compliance as GTN application is associated with severe headaches in some patients.
Trial website
none
Trial related presentations / publications
none
Public notes
none

Contacts
Principal investigator
Name 38214 0
Dr Muhammad Asim
Address 38214 0
Department of colorectal surgery, Waikato Hospital, Pembroke street, Hamilton. 3204
Country 38214 0
New Zealand
Phone 38214 0
+64211448889
Fax 38214 0
Email 38214 0
aasim166@yahoo.com
Contact person for public queries
Name 38215 0
Dr Muhammad Asim
Address 38215 0
Department of colorectal surgery, Waikato Hospital, Pembroke street, Hamilton. 3204
Country 38215 0
New Zealand
Phone 38215 0
+64211448889
Fax 38215 0
Email 38215 0
aasim166@yahoo.com
Contact person for scientific queries
Name 38216 0
Mr Simione Lolohea
Address 38216 0
Colorectal surgeon, Department of Colorectal Surgery, Waikato Hospital, Hamilton. 3204
Country 38216 0
New Zealand
Phone 38216 0
+64274822382
Fax 38216 0
Email 38216 0
similolohea@gmail.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary