Efficacy of Polyethylene Glycol vs Lactulose With Isabgol in Acute Fissure-in-Ano: PEGASIS Trial

Study Overview
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Brief Summary
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The existing literature stresses the better efficacy of polyethylene glycol (PEG) over other stool softeners like lactulose or isabgol to improve functional constipation. But there is no consensus regarding the efficacy of PEG alone vs lactulose combined with isabgol used as stool softeners, frequently used for relieving acute constipation in an acute fissure in ano. Hence a good quality randomised study to compare both efficacies is the need of the hour.

Detailed Description
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Acute fissure in ano is a very common, painful and distressing benign anorectal disorder. It is a linear tear in the anoderm of the distal anal canal most commonly on the posterior midline. They usually result from trauma caused by the passage of hard stool and less commonly from diarrhoea also. The most common presenting symptom is anal pain, bleeding and secondary constipation. Most of the cases are managed conservatively by increasing oral fluid intake, high fibre diet, sitz bath, stool softeners and topical application of sphincter muscle relaxants. Constipation is one of the most common causes of anal fissure. Patients present to the outpatient department due to acute anal pain resulting from increased internal anal sphincter tone with spasms and hard stool rubbing over the crack. Constipation and pain due to anal fissure are initially managed with lifestyle and dietary modifications like consuming adequate fluids, increased fibre diet and sitz bath. One of the fibre supplements is isabgol husk, a soluble fibre with enormous water-absorbing properties. Its added benefits include properties like non-irritant to the large bowel, non-fermenting, and dichotomous stool normalising agents, making it one of the most preferred bulk-forming agents. Low cost and over the counter availability are other benefits. Lactulose is also the most commonly prescribed laxative used in acute anal fissures to relieve constipation. Polyethylene glycol is a common osmotic laxative used for the relief of constipation in the treatment of anal fissures. There are multiple studies that say polyethylene glycol has better efficacy in terms of frequency of stools, and form of stools compared to lactulose or isabgol husk alone. However, there are no studies conducted to compare the efficacy of polyethylene glycol vs combined use of isabgol husk and lactulose in relief of constipation in an acute fissure in ano. However, studies prove that laxatives may reduce/delay the absorption of certain medications, hence medications are advised to be taken 1 hour before or 2-3 hours after taking laxatives. Patients in both arms will be advised to use local lidocaine with nifedipine cream (Anobliss cream from Samarth Life Sciences Pvt. Ltd., India). One arm will be given polyethylene glycol syrup for 2 weeks maximum and in the other arm, isabgol husk plus lactulose will be given for 2 weeks. Patients will be assessed at the end of a week, and 1 month and evaluated for primary and secondary outcomes.

Official Title
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Efficacy of Polyethylene Glycol vs Lactulose With Isabgol in Acute Fissure-in-Ano: A Randomized Control Trial (PEGASIS Trial)

Conditions
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Anal Fissure, Constipation

Intervention / Treatment
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* Drug: Polyethylene Glycol
* Drug: Isabgol + Lactulose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients presenting with acute fissure in ano between the age group of 18 to 75 years. Exclusion Criteria: Pregnancy / lactation Patients not giving consent Patients not able to understand the nature of the study Diabetes mellitus and chronic kidney disease Known intolerance to PEG/Lactulose or Isabgol Prior enrolment in other study. Patient undergoing surgery for Fissure in Ano

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Study group 1(Polyethylene Glycol)<br>Polyethylene glycol syrup will be used at a dose of 15-30 ml per day for 2 weeks maximum. | Drug: Polyethylene Glycol<br>* Patients will be advised Anobliss (lidocaine with nifedipine) ointment for local application in the anal canal for one month for relief of pain and anal sphincter spasm. Polyethylene glycol syrup at a dose of 15-30 ml will be used for 2 weeks for relief of acute constipation. Patients will be assessed at 1 week and 1 month and evaluated for primary and secondary outcomes.<br>* Other names: Freego PEG oral solution from Alembic Pharmaceuticals Ltd.;|
| Active Comparator: Study group 2 (Isabgol and Lactulose)<br>Isabgol 2 teaspoons in 200ml of warm water to consume immediately after soaking before bedtime and syrup Lactulose 30 ml at bedtime for 2 weeks. | Drug: Isabgol + Lactulose<br>* Patients will be advised Anobliss (lidocaine with nifedipine) ointment for local application in the anal canal for one month for relief of pain and anal sphincter spasm. Isabgol husk at a dose of 2 teaspoons in 200 ml of warm water before bedtime and 30 ml of syrup lactulose at bedtime will be used for 2 weeks for relief of acute constipation. Patients will be assessed at 1 week and 1 month and evaluated for primary and secondary outcomes.<br>* Other names: Duphalac oral solution from Abbott;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time taken for the resolution of acute pain following fissure in ano. | Pain will be measured by improvement in visual analog scale (VAS) pain score. Scores will be recorded by making a handwritten mark on a 10-cm line that represents a continuum between no pain (score of 0) and worst pain (score of 10). | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in constipation will be assessed by a change in the Bristol stool form scale. | Acute constipation is the cause and result of acute fissure-in-ano. Stool softeners help in alleviating the pain by improving the stool forms assessed by Bristol stool scale. Type 1-2 indicates constipation that exacerbates the pain in an acute fissure in ano. Type 3-4 are ideal stools and easier to pass and Type 5-7 are soft to liquid stools that will be much helpful in alleviating the pain in an acute fissure in ano. | 1 week, 1 month | 
| Adverse effects any of PEG or lactulose with isabgol. | Long term use of PEG or lactulose can result in electrolyte imbalance, diarrhoea, or stomach cramps. Incidence of adverse effects if any will be recorded and reported. | 1 month | 
| Patient compliance with the medications | The compliance with the drugs will be recorded at the end of one month through personal interviews based on TSQM version 1.4 questionnaire. | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute fissure in ano, Constipation, Lactulose, Isabgol, Polyethylene Glycol