Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT03920449 |
| Other study ID # |
R/19.02.418 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 1, 2019 |
| Est. completion date |
January 1, 2021 |
Study information
| Verified date |
May 2020 |
| Source |
Mansoura University |
| Contact |
Mostafa Shalaby |
| Phone |
00201001645917 |
| Email |
mostafashalaby[@]mans.edu.eg |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
We hypothesized that optimization of the dose of the Botulinum toxin injection (BT) and
standardization of the technique of lateral internal sphincterotomy to posterolateral
internal sphincterotomy (PIAS) could, in turn, report a conclusive result which helps to
provide better care to patients with chronic anal fissure. So, we will conduct this trial as
a prospective randomized, controlled, intervention, open-label trial with two parallel
groups, and a primary endpoint of fissure healing during 6 months after the initial
intervention, with the randomization, will be performed by an online software with a 1:1
allocation. Eligible patients will be randomized in equal proportions between BT injection
and PIAS.
Description:
2.1 Trial design This trial will be designed as a prospective randomized, controlled,
intervention, open label trial with two parallel groups, and a primary endpoint of fissure
healing during 6 months after initial intervention, with the randomization will be performed
by an online software with a 1:1 allocation.
2.3 Pre-enrollment After careful history and clinical examination, the diagnosis of chronic
anal fissure will be considered when a wider and deeper ulcer with keratinous edges, presence
of a sentinel tag at the external apex, hypertrophy of the anal papillae, and exposed
internal anal sphincter (IAS) smooth muscle fibers, will be exist. As a routine in Mansoura
colorectal surgery unit, any patient above 50 years old will be scheduled for colonoscopy to
rule out colorectal cancer, as well as, those associated with bleeding per rectum or other
risk factors. Additionally, patients will be evaluated for constipation by preoperative and
6th-months postoperative Wexner Constipation Score and for their continence status by
preoperative and 6th-months postoperative Fecal Incontinence Severity Index (FISI) and
Anorectal Manometry. Preoperative mechanical bowel preparation will not be indicated,
however, single enema in the day of the procedure will be advised in order to facilitate
examination under anesthesia (EUA) which is a mandatory initial step in all begin anorectal
procedures in our unit. Appropriated thromboembolic prophylaxis will be prescribed based on
the patient risk stratification.
2.4 Interventions Eligible patients will be randomized in equal proportions between Botulinum
Toxin (BT) injection and Posterolateral Internal Anal Sphincterotomy (PIAS). All procedures
will be performed under spinal anesthesia with the patient in modified lithotomy position by
senior consultant colorectal surgeons or under their direct supervision. At the time of the
anesthesia induction, 500 mg metronidazole will be administrated. All procedures will be
preceded by gentle anal dilatation, insertion of an anal retractor, and EUA. Subsequently,
the surgeon will proceed to the allocated intervention.
In group I (BT injection), 21 U will be injected in 3 divided doses through the internal anal
sphincter at 3,9, and 12 o'clock. In the Egyptian market two commercial forms are available;
botulinum toxin type A (Botox 100 IU/vial; Coolock, Dublin, Ireland), and abobotulinumtoxin A
(Dysport 500 U/vial; Ipsen Biopharm Ltd, Wrexham, UK). In case of Dysport it should be
remembered that dosing is on a ratio of approximately 1 to 3, meaning that 50 IU of Botox
have the same effect as 150 IU of Dysport.
In group II (PIAS), A 1.5 to 2-cm circumferential skin incision will be placed at 5 o'clock
position outside the anal verge using an electrocautery device. Dissection will be proceeded
through the intersphincteric groove to separate both IAS and external anal sphincter (EAS).
Then, the IAS will be identified by its characteristic white fibers, separated from the anal
mucosa, and assessed under direct vision. Subsequently, about 50 % of the IAS will be divided
at 5 o'clock position and any skin tags or hypertrophied anal papillae will be removed
leaving the skin incision open to allow drainage.
In both groups, the procedure will be followed by application of direct pressure for 5
minutes. The fissure will not be curetted or debrided in any way. All patients will be
discharged on the 1st postoperative day with recommendations to use stool softener, bulking
agents, a high-residue diet, and warm sitz baths for three weeks to reduce pain and avoid
constipation and bleeding. On demand analgesics in form oral ketorolac 10 mg will be
permitted.
2.5 Patient's follow-up For the end-points of the study, all patients will be followed-up in
the outpatients' department for a period of six months. The follow-up schedule will be as
follow, at every week for the first month, then at the end of the 2nd, 3rd, 4th, 5th, and 6th
months. However, patients will be advised to visit the outpatients' department at any other
time point during the trial if they developed any unfavorable event. At each visit, the ulcer
will be inspected visually with the percent of re-epithelization will be measured
subjectively. The resolution of initial symptoms, anal pain and/or bleeding will be
addressed. The pain will be measured at each visit by the Visual Analog Scale (VAS) ranged
from no pain "0" to worst pain "10".
2.7 Sample Size Calculation Based on a power analysis and sample size calculation, the
desired sample size for this study will be 25 for each group of intervention. Given an
expected medium effect size of 0.5 and p <0.05, this will lead to the acceptable power of
0.80. In order to compensate for drop-out and losses to follow-up, 30 patients will be
initially included. The sample size will be calculated using an online software
(http://clincalc.com/stats/samplesize.aspx) with the healing rate using BT injection will be
considered 71.4% according to Sahebally et al (6) and the healing rate for PIAS will be
considered 99% according to Alawady et al (10).
2.8 Randomization; sequence, generation, allocation, and implementation All participants who
will give consent for participation and who will fulfil the inclusion criteria will be
randomly assigned to either BT injection and PIAS with a 1:1 allocation as per an online
software (https://www.graphpad.com/quickcalcs/randomize2/) generated randomization schedule.
Randomization will be requested by a staff member who will not take any part in patients'
care, follow-up, data collection/analysis or accessing outcomes of the study. In return, this
staff member will schedule an answer form with a randomization plan which will be formed of 2
sets; each set will contain unique 30 numbers arranged from the smallest to the largest with
the whole 60 numbers ranging from 1 up to 60. Each set labeled with one of group allocation;
BT injection or PIAS. Then, the staff member will be interpreting this form into 60 sealed
envelopes with the patients' number written upon it and the allocated procedure inside and
send these sealed envelopes the department's senior resident. On the day of the procedure,
the sealed envelope will be opened 2.9 Blinding This study will be open label unblinded
clinical trial in which patients and surgeons will be aware of the nature of the procedure,
however, data collectors, those assessing the outcomes, and data analyzer will all be blinded
to the allocation until the end of the trial.
