| In all anorectal disorders Constipation is the primary cause . Fissure in
Ano (AF) is the most common disease reported in Anorectal Clinics. Anal fissure
(AF) is the longitudinal linear cut in the anoderm, generally located at the posterior
midline. The incidence of AF is 1 in 350 adults whereas prevalence rate of Acute
Fissure is 18% in Anorectal Disorders. Even though, it is a superficial and small
ulcer but a distressing lesion. Severe cutting/ tearing type of pain, local burning
sensation, bleeding per rectum are the common clinical features of Fissure in Ano.
In a study, conducted on impact of AF in Patient’s Quality of life, showed that
patients suffer significantly in vitality, bodily pain, social functioning and mental
health.5 The treatment protocol includes Injection of botulinum toxin, application
of lignocaine, diclofenac suppository for the pain management of Acute Fissure in
Ano. Though they reduce pain and burning sensation transiently, they do not help
in healing of the ulcer but exhibit several adverse effects like temporary anal
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incontinence of flatus by injection of botulinum toxin 4. Although the use of topical
lidocaine and diclofenac suppository is considered relatively safe, instances of
cardiotoxic and neurotoxic adverse events have been reported. The sequence of
events related to the central nervous system after a progressive increase of local
anesthetic agent and Diclofenac is as follows: paresthesia, dizziness or light
headedness, drowsiness, local irritation etc.6 The use of topical nitrates has led to
headache and calcium Channel blockers lead to itching.7 The standard treatment for
AF is Lateral sphincterotomy which is associated with the risk of long-term anal
incontinence. Thus, there is a need of new treatment modalities for Acute Fissure
in Ano with minimal side effects.
Various scientific studies have been carried out to substantiate the
efficacy of Ayurvedic approaches in the management of Acute fissure-in-ano,
which is corelated to the condition called as Parikartika. Acharya Sushruta
considers Parikartika as a poorvaroopa of Arshas 8, Virechana Vyapath 9 and
Basti Vyapath. The Acharya has mentioned one of the treatment of Parikatika as
Yashtimadhu Taila Anuvasana Basti. In Kashyapa Samhita, Acharya has
mentioned oral administration of Yashtimadhu Choorna and madhu for licking
by Pregnant woman in Parikartika. The studies conducted at different academic
and research institutes like Local application of Jatyadi ghrita, Jatyadi
taila,Yashtimadhu taila, Prabhakara ghrita, Kasisadi Taila, Nimbadi taila,
Vranaropana taila, Doorvadi ghrita, Ghrita Manda, Yashtimadhu Ghrita,
Vedanantaka Malahara, different types of Pichu and internal administration of
Abhyarishta, Kutajarista, Triphala Churna have proven an edge over the
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conventional therapies in managing the symptoms viz. pain, bleeding besides
healing of ulcer. Adding to this the achievement of bowel regulation is
significantly observed in all these studies indicating the uniqueness of Ayurvedic
approaches.
A thorough review of scientific study to validate the Ayurvedic
approaches in fissure-in-ano revealed that the management with Guda Varti (anal
suppository) has not been given the emphasis. Anal Suppository being a modality
of drug delivery that certainly enhances the tissue contact time of the drug and
improving the bio availability in comparison to conventional local application of
drugs. In the similar way, suppositories melt and exert local or systemic effects.
They are used to deliver both systemically and locally acting medications. Topical
use of Yashtimadhu Ghrita is indicated in Shastranipataja Vrana, a Sadyovrana,
for the pain management. A clinical study was conducted in our hospital on
Yashtimadhu ghrita Suppository in Post operative pain management of Arshas.
The study has shown good result with p value <0.001. Fissure in Ano is a traumatic
wound (Sadyo Vrana) caused by the passage of hard stools or by increased
frequency of watery stools. So, a pilot study was conducted on the management of
Acute Fissure in Ano with Yashtimadhu ghrita Suppository, which has shown
encouraging result. Hence, here an effort will be made to evaluate the efficacy of
Yashtimadhu ghrita Suppository in Acute fissure in Ano, in comparison with
Yashtimadhu Ghritapoorna .
Objectives of the study: Primary Objectives: 1. To evaluate the efficacy of Yashtimadhu Ghrita Suppository in the management
of Acute fissure in ano. 2.To evaluate the efficacy of Yashtimadhu Ghritapoorna in the management of
Acute fissure in ano. 3. To compare the clinical efficacy of both Suppositories in the management of
Acute fissure in ano
Secondary Objectives: 1. To standardize the Yashtimadhu Ghrita suppositories by conducting
Analytical Study like Stability test
Material and methods i. Source of data The subject irrespective of the gender diagnosed as Acute Fissure in Ano will be
selected from OPD and IPD of JSS Ayurveda Medical College and Hospital,
Mysore. The subjects will be screened, registered and after taking the consent
will be intervened on in-patients and out-patients with the help of case sheet
proforma specially prepared for the study. Literary source: Brihatrayi, Laghutrayi, contemporary literature and literature including the
website about the disease, drug and procedure will be reviewed and documented
for the intended study. Drug source:
Yashtimadhu Ghrita Suppository will be prepared in JSS Ayurveda Pharmacy
and Yashtimadhu Ghritapoorna will be procured from local Pharmacy, Mysore.
18 ii. Method of Collection of data
Sampling Method and Sample size: 300 subjects diagnosed as Acute Fissure
in Ano will be allocated to standard group (Group A) 150and trial group (Group
B) 150 each. Study design: It is a randomized open label comparitive clinical study
Sampling technique: 1.The subjects who fulfil the inclusion criteria and complying with the informed
consent (IC) will be selected using random sampling (lottery method) technique. 2. A special case proforma containing all the necessary details pertaining to the
study will be prepared.
3. The data obtained in all groups will be recorded, tabulated and statistically
analysed. Sample size: Sample size calculated using the formula (1.96)2 pq/d2 where 1.96 is the constant,
p is the prevalence = 0.183, q is (1 - p) = 0.82 and d is the significance level =
0.05. Thus, the sample size required for the study becomes 300 considering the
dropouts of the subjects.
Method of collection of data:
300 subjects who fulfil the inclusive criteria irrespective of gender, religion,
economic status will be selected for the study using random sampling technique
(lottery method). Diagnostic Criteria: Based on the history and per rectal examination findings, sign and symptoms like
Cutting type of pain, Pain during defecation, passage of bright streaks of blood
along with stool or seen in the tissue paper, sphincter spasm will be diagnosed as
Acute Fissure in Ano. Inclusion Criteria: • Subjects exhibiting signs & symptoms of Acute Fissure-in ano <6 weeks23
superficial, having well-demarcated edges and confirmed by anorectal
examination. • Irrespective of gender and aged between 18-60 years. • Subjects who are willing to sign the informed consent form Exclusion Criteria: • Chronic Fissure in Ano with hypertrophied anal papilla at the proximal aspect of
the fissure, a sentinel tag at the distal aspect of the fissure, keratinous edges and/or
exposed internal anal sphincter muscle within the base of the fissure.23 • Acute Fissure in Ano secondary to Crohn’s disease, Ulcerative Colitis, Irritable
Bowel Syndrome, Tuberculosis of the Intestine, Haemorrhoids, Proctitis, Fistula In
Ano and other Ano rectal Disorders. • Subjects with anal or perianal malignancy. • Female Subjects who are pregnant or lactating. • Subjects with Congenital anomalies of rectum and anal canal • Subjects with Autoimmune Disease, Anal Suppuration, Anal Abscesses. • Subjects with any malignancies or any sexually transmitted diseases • Subjects with systemic disease like AIDS, TB, HBV, HCV, Uncontrolled
Diabetes Mellitus, Uncontrolled Hypertension, Chronic Liver Disease, Renal
Failure • Subjects currently participating in another clinical trial for any document or has
participated in any clinical trial in the last 90 days. Operational Definitions / Techniques Employed: METHOD OF PREPRATION OF DRUG: SOURCE: Collection of the Yashtimadhu will be done from the local raw drug
vendor at Mysuru. AUTHENTICATION:
Raw drug authentication will be done in Dept. of Dravyaguna & Yashtimadhu
Ghrita prepared will be Authenticated by the Department of Rasashastra &
Bhaishajya Kalpana, JSS Ayurveda Medical College & Hospital, Mysuru. PREPARATION OF YASHTIMADHU GHRITA SUPPOSITORY:
Sterile base material of Cocoa butter and beewax in the proportion of 1.5: 0.5
respectively will be melted on water bath for avoiding local heating. Later 2 parts
of Yastiamdhu Gritha will be suspended in it. The mass will be poured into
lubricated moulds of 2g18 and freezed for 10-15mins. Gently suppositories will
be removed from moulds under sterile condition and stored in an 5-3 degree celsius
in air tight container under sterile condition. STUDY DESIGN: 300 diagnosed subjects of Acute Fissure-in-Ano will be selected and randomly
assigned into 2 groups, namely Standard and Trial comprising of 150 subjects
each. INTERVENTION: Standard group (Group-A): Poorva Karma - Complete evacuation of bowel • Sukhoshnajala Avagaha Sweda (Sitz Bath) for 20 minutes twice daily. Pradhana Karma - In left lateral position, the subject is advised to insert
Yashtimadhu Ghrita into anal canal 5ml, twice daily for 15 days Paschat Karma- Advised to lie down in supine position for 5 minutes
The subject is advised to maintain the hygiene. Tab Triphala Guggulu 2-0-2 after food for 15 days Trial group (Group-B): Poorva Karma - Complete evacuation of bowel • Sukhoshnajala Avagaha Sweda (Sitz Bath) for 20 minutes twice daily. Pradhana Karma - In left lateral position, the subject is advised to insert two
suppositories of 2g Yashtimadhu Ghrita into anal canal, twice daily for 15 days. Paschat Karma- Advised to lie down in supine position for 5 minutes
The subject is advised to maintain the hygiene. Tab Triphala Guggulu 2-0-2 after food for 15 days ASSESSMENT SCHEDULE: Assessment will be done on Before Treatment (BT) and at the end of every week
for 4 weeks. Intervention: 2 weeks
Follow up: At 3rd week and 4th week Total duration of the study: 4 weeks
2 weeks of intervention or till the complete healing of fissure whichever is earlier
and 2 weeks of follow up at 3rd and 4th week. Total number of assessment-5 Pre-test on zero day Number of mid test -3 at the end of every week (1st,2nd,3rd) Post-test at the end of 4th week. (2nd follow up) ASSESSMENT CRITERIA: The assessment will be done based on the signs &symptoms relief by grading
once at the end of week. The following criteria will be considered for the
assessment of improvement: • Pain – Nature of pain, Impact on quality of life, character of pain, duration of pain • Bleeding per Rectum • Ulceration in anus • Sphincter tone • Number of days taken for the wound healing SUBJECTIVE CRITERIA • Nature of the pain - Defense and Veterans pain rating scale 0 - No pain, 1- Hardly noticeable pain, 2- Noticeable pain, but does not interfere
with activities ,3- Somewhat distracting pain, 4 -Distracting pain but does not affect
normal activities, 5- Pain interrupts some activities, 6- Hard to ignore pain,
avoidance of daily activities, 7- Pain is the main focus of attention, prevents daily
activities, 8-Awful pain, difficult to do anything , 9-Unbearable pain, cannot do
anything,10-As bad as pain can be, nothing else matter. • Disease impact on quality of life - REALISE scoring (Scoring system for anal
fissure)25
How much does Fissure-in-ano impact your quality of life?
1 – No impact, 2 – Slightly, 3 – Moderately, 4 – Considerably, 5 – Severely.
• Character of pain - Mcgill pain index score26
0 – No pain, 1 – Mild pain, 2 – Discomforting pain, 3 – Distressing pain, 4 –
Horrible pain, 5 – Excruciating pain. • Duration of pain - REALISE scoring25
0 – No pain, 1 – Pain less than 1 hour after defecation, 2 – Pain remains 1-2 hours
after defecation, 3 – Pain remains 2-4 hours after defecation, 4 – Pain remains more
than 4 hours. • Bleeding per rectum- REALISE scoring25
How often does bleeding from the anus occur?
1-Never, 2- Rarely (less than 25% of defecations), 3-Sometimes (More than
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25% and less than or equal to 50% of defecations), 4- Often (More than 50%
and less than or equal to 75% of defecations), 5- Always (more than 75% of
defecations) OBJECTIVE CRITERIA • Ulceration in anus
During Digital Rectal Examination (DRE)
0-Absent, 1- Present • Length of the Ulcer
Length of the ulcer will be measured using the glass pipette. • Bleeding per rectum
During DRE
0-Absent, 1- Present • Sphincter tone27
During DRE, As per DRESS Resting Score,
0- No discernable tone at rest, an open or patulous anal canal, 1- Very low tone, 2
Mildly decreased tone, 3-Normal, 4-Elevated tone, snug, 5-Very high tone, a tight anal
canal, difficult to insert a finger. • Number of days taken for the wound healing: in Numericals
LABORATORY INVESTIGATIONS:
1. Blood Investigations - Hb%, RBC Count, Platelet Count, BT, CT, blood urea,
serum creatinine, TC, RBS, ESR, HBsAg (spot method), HIV (spot method), LFT
(Before and After the intervention)
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2. Urine routine
3. TRUS and Colonoscopy if required
DROP OUTS
An attempt shall be made to record the reason for dropouts, if any during the clinical
trial. RECORDING AND REPORTING OF ADVERSE DRUG REATION (ADR): Any adverse event, observed during treatment period or during follow up visits will
be clearly documented using ADR form (attached) and appropriate and timely
management will be done consulting the physician /consultant associated in the
trial. The investigating team will report the same to the Ethics committee at the
earliest. DRUG COMPLIANCE: If there is more than or equal to 80% compliance, the participant would be
continued in the trial. The compliance needs to be assessed at each visit during the
follow up by counting the number of empty container/sachets /bottles returned and
assessing the approximate quantity of medicine consumed by the patient. CONCOMITANT MEDICATION: Details of concurrent illness / medications consumed by the participants registered
under the trial will be recorded in case report form. Registered patients will be
instructed to avoid the use of any other drugs on their own for any ailment and will
be clearly instructed to consult the treating investigating physician for any symptom
or complaints, or if they feel anything unusual. The investigating physician will
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record any medication(s) he/she may prescribe to alleviate their ailments. RESCUE MEDICATION FOR INTERCURRENT ILLNESS: To alleviate any emergency, the use of rescue medication is permitted as per the
wisdom discretion of the principal investigator. However, the same will be
documented in appropriate column in the Case Record Form STATISTICAL TESTS TO BE USED: Data will be collected using case report form (CRF) designed by incorporating all
aspects (Ayurveda & modern medicine) for the study. Such collected data will be
tabulated and analyzed using SPSS (Statistical package for social sciences) version
21 by using appropriate statistical test. Demographic data and other relevant
information will be analyzed with descriptive statistics. Continuous data will be
expressed in mean+/- standard deviation, and nominal and ordinal data will be
expressed in percentage. Nominal & ordinal data will be analyzed using non
parametric tests like Friedman’s test, Wilcoxon’s signed rank test, Mann Whitney
test. The changes (one tailed) with p value<0.05 will be considered as statistically
significant. |