Clinical trial NCT05341180: Efficacy of Polyethylene Glycol vs Lactulose With Isabgol in Acute Fissure-in-Ano: PEGASIS Trial
Official title: Efficacy of Polyethylene Glycol vs Lactulose With Isabgol in Acute Fissure-in-Ano: A Randomized Control Trial (PEGASIS Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Anal Fissure
Constipation
Keywords: Acute fissure in ano
Constipation
Lactulose
Isabgol
Polyethylene Glycol
Lead sponsor: All India Institute of Medical Sciences, Bhubaneswar
Sponsor class: OTHER
First posted: 2022-04-22
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Time taken for the resolution of acute pain following fissure in ano.
timeFrame: 30 days
Secondary outcomes:
measure: Improvement in constipation will be assessed by a change in the Bristol stool form scale.
timeFrame: 1 week, 1 month
measure: Adverse effects any of PEG or lactulose with isabgol.
timeFrame: 1 month
measure: Patient compliance with the medications
timeFrame: 1 month
Other outcomes:
Locations:
city: Bhubaneswar
country: India
facility: All India Institute of Medical Sciences
state: Odisha
Study officials:
affiliation: Department of General Surgery, All India Institute of Medical Sciences, Bhubaneswar, Odisha, INDIA
name: Prakash Kumar Sasmal, MBBS, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.