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

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

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.

Study Overview

• Status: Completed
• Conditions: Constipation; Anal Fissure
• Intervention / Treatment: Drug: Polyethylene Glycol; Drug: Isabgol + Lactulose

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 144
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• India
  • Odisha
    • Bhubaneswar, Odisha, India, 751019
      • All India Institute of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Study group 1(Polyethylene Glycol); Polyethylene glycol syrup will be used at a dose of 15-30 ml per day for 2 weeks maximum.	Drug: Polyethylene Glycol; 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.; Other Names: Freego PEG oral solution from Alembic Pharmaceuticals Ltd.
Active Comparator: Study group 2 (Isabgol and Lactulose); 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; 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.; Other Names: Duphalac oral solution from Abbott

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: All India Institute of Medical Sciences, Bhubaneswar
• Investigators: Principal Investigator: Prakash Kumar Sasmal, MBBS, MS, Department of General Surgery, All India Institute of Medical Sciences, Bhubaneswar, Odisha, INDIA

Publications and helpful links

General Publications

• Nelson RL, Thomas K, Morgan J, Jones A. Non surgical therapy for anal fissure. Cochrane Database Syst Rev. 2012 Feb 15;2012(2):CD003431. doi: 10.1002/14651858.CD003431.pub3.
• Lee-Robichaud H, Thomas K, Morgan J, Nelson RL. Lactulose versus Polyethylene Glycol for Chronic Constipation. Cochrane Database Syst Rev. 2010 Jul 7;(7):CD007570. doi: 10.1002/14651858.CD007570.pub2.
• Wang HJ, Liang XM, Yu ZL, Zhou LY, Lin SR, Geraint M. A Randomised, Controlled Comparison of Low-Dose Polyethylene Glycol 3350 plus Electrolytes with Ispaghula Husk in the Treatment of Adults with Chronic Functional Constipation. Clin Drug Investig. 2004;24(10):569-76. doi: 10.2165/00044011-200424100-00002.
• Tomatsu S, Dieter T, Schwartz IV, Sarmient P, Giugliani R, Barrera LA, Guelbert N, Kremer R, Repetto GM, Gutierrez MA, Nishioka T, Serrato OP, Montano AM, Yamaguchi S, Noguchi A. Identification of a common mutation in mucopolysaccharidosis IVA: correlation among genotype, phenotype, and keratan sulfate. J Hum Genet. 2004;49(9):490-494. doi: 10.1007/s10038-004-0178-8. Epub 2004 Aug 11.
• Belsey JD, Geraint M, Dixon TA. Systematic review and meta analysis: polyethylene glycol in adults with non-organic constipation. Int J Clin Pract. 2010 Jun;64(7):944-55. doi: 10.1111/j.1742-1241.2010.02397.x.

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2022
• Primary Completion (Actual): July 20, 2023
• Study Completion (Actual): July 22, 2023

Study Registration Dates

• First Submitted: April 10, 2022
• First Submitted That Met QC Criteria: April 16, 2022
• First Posted (Actual): April 22, 2022

Study Record Updates

• Last Update Posted (Actual): July 25, 2023
• Last Update Submitted That Met QC Criteria: July 21, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Constipation; Polyethylene Glycol; Lactulose; Acute fissure in ano; Isabgol
• Additional Relevant MeSH Terms: Digestive System Diseases; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Anus Diseases; Constipation; Fissure in Ano; Gastrointestinal Agents; Lactulose; Pharmaceutical Solutions
• Other Study ID Numbers: IEC/AIIMS BBSR/PG Thesis/

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No