Efficacy of Polyethylene Glycol vs Lactulose With Isabgol in Acute Fissure-in-Ano: A Randomized Control Trial (PEGASIS Trial)
Phase: PHASE2
Conditions: Anal Fissure, Constipation
Sponsor: All India Institute of Medical Sciences, Bhubaneswar

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 PROTOCOL OF THESIS FOR THE PARTIAL FULFILLMENT OF  
MS DEGREE IN GENERAL SURGERY 
 
 
 
 
 
 
 
 
 
“Efficacy of Polyethelene Glycol vs Lactulose with Isabgol in Acute fissure-in-Ano:  
A Randomized Control Trial. (PEGASIS trial)” 
 
 
 
 
All India Institute of Medical Sciences 
Bhubaneswar – 751019 
 
 
 
 
 

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                                                                  Candidate: 
                                                    Dr. Aitha Saikrishna 
Academic Junior Resident. 
Department of General Surgery. 
                                                     saisurya.aitha@gmail.com 
8919330687 
 
  Chief guide: 
                                             Dr. Prakash Kumar Sasmal 
Additional Professor 
Department of General Surgery 
drpksasmal@gmail.com 
9438884255 
 
                                                           Co-guide: 
                                                    Dr. Pankaj Kumar 
                                                Associate Professor 
                                            Department of General Surgery 
                                                        9711090814 
                                                   
                                               

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Consent of Guide, Co-guide and Head of Department 
 
Title of thesis:  
“Efficacy of Poly Ethelene Glycol vs Lactulose with Isabgol in Acute fissure-in-Ano:  
A Randomized Control Trial. (PEGASIS trial)" 
 
Signature of the Candidate                                                                     
 
 
Signature of Guide                                                                        
 
 
Signature of Co-Guide  
 
                                                                  
 
 
Signature of HOD 
 

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Table of content 
 
 
Sl. No. 
Content 
Page Number 
1. 
IEC Format 
05 
2. 
Introduction 
14 
3. 
Study Objectives 
16 
4. 
Review of Literature 
17 
5. 
Materials and Methods 
18 
6. 
Ethical Issues 
22 
7. 
Timeline 
23 
8. 
References 
24 
9. 
Annexures 
25 
 
 
 
 
 
 
 
 
 
 
 

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IEC FORMAT FOR POSTGRADUATE THESIS PROTOCOL 
 
1. Full Title of Study: 
Efficacy of Polyethelene Glycol vs Lactulose with Isabgol 
in Acute Fissure-in-Ano: A Randomized Control Trial. 
(PEGASIS trial) 
2.1 Name & signatures of the candidate 
 
 
  
 
2.2 Department 
 
2.3 Degree/course 
 
2.4 Batch of admission to the course 
 
2.5 Month & year of submission of thesis 
     
Dr Aitha Saikrishna 
 
 Signature________________ 
 
 
General Surgery 
 
MS 
       
July 2021 
 
Dec 2023 
3. Name of Faculty & Department     
   (Chief-Guide/Co-guide) 
 
 
 
Signatures (Chief-Guide/Co-Guides) 
 
 
 
 

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a. Dr. Prakash Kumar Sasmal 
Additional Professor  
Department of General Surgery 
 
b. Dr. Pankaj Kumar 
Assosiate professor 
Department of General Surgery 
 
 
 
3.1_____________________________________________ 
 
 
 
3.2 ____________________________________________ 
 
 
 
4. Objectives of the study 
 
 
Primary objective 
• 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). 
 
Secondary objectives 
• Improvement in constipation will be assessed by a 
change in the Bristol stool form scale. Acute 

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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. 
• 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. 
• 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. 
 
5. Why this study is required?  
    Please provide a brief justification.  
• 
The existing literature stresses upon the better 
efficacy of PEG over other stool softeners like 
lactulose or isabgol for functional constipation.(1,2)  

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• 
And there is no consensus regarding PEG vs lactulose 
combined with isabgol as stool softeners, which we 
frequently use for treating acute fissure in ano. 
• 
Hence a good quality RCT is the need of the hour. 
6. Methodology  
 
 
 
 
6.1. Study Design: Randomized Control Trial 
6.2. Study Setting: Outpatient department, Department of 
General Surgery, All India Institute of Medical Sciences, 
Bhubaneswar. 
 
6.3. Study Groups:  2 Groups 
 
6.4. Sample size: Sample size is a total of 144,  72 in each 
group which is calculated using Kelsey Fleiss corrected 
formula in the openepi.com. 
 
 
6.5. Inclusion criteria 
§ All patients presenting with acute 
fissure in ano between the age group 
of 18 to 75 years. 
6.6 Exclusion criteria 
§ Pregnancy / lactation 
§ Patients not giving consent 

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§ 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 
 
6.7. Details of Control(s) NA 
 
6.8. Details of intervention Administration of Polyethylene 
glycol in one group, isabgol husk and lactulose in the other 
group in the recommended dosage to relieve acute 
constipation. Sphincter relaxants will be also used as local 
application of Nifedipine with Lignocaine (Anobliss 
ointment from Samarth Lifesciences Pvt. Ltd., India) in both 
the groups along with warm water sitz bath. 
6.9. Duration of study: Two years  
6.10. Outcome measures:  
• Pain will be assessed by VAS score 
• Presence or absence of bleeding 

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• Stool consistency measured by Bristol stool form 
scale 
• Rate of ulcer healing at one month 
• Patient compliance to the medications based on 
TSQM version 1.4 questionnaire.                       
 
6.11. Investigation specifically related to Protocols: no 
specific investigation needed 
 
6.12. Permission to use copyrighted 
Questionnaire/proforma: NA 
 
6.13. Others: NA 
7. Permission from Drug Controller    
    General of India (DCGI) 
 
1.        Required          2.        Not required 
3.        Received          4.        Applied when:                 
8. Permission from DGFT, if required 
 
 
1.        Required          2.        Not required 
3.        Received          4.        Applied when:                 
9. a) Safety measures for proposed  
        interventions 
    b) Results of relevant laboratory tests 
    c) Result of studies in human 
a) NA 
 
      b) NA 
      c) NA 

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10.  Plans to withdraw standard therapy  
      in research  
 
 
                     Yes                         No 
 
Remarks:_______________________________________ 
 
11. Plan for the provision of coverage for  
      medical risk  
 
 
No specific provision of coverage for medical risk is 
provided. 
 
 
12. How you will maintain          
      Confidentiality of the subject? 
Confidentiality of the subjects will be ensured and will not be 
shared before, during, and after the study. 
13. Costs Involved (Appx. in Rs.) 
 
13.1 Investigations 
 
13.1.1 List of Investigations required in 
the study which are part of the routine 
workup 
 
13.1.2 List of Investigations required in 
the study which are NOT part of routine 
Rs 37,000/-  for medicines 
Rs 3000/- for printing of charts and questionnaires 
 
 
 
NA 
 
 
 
13.1.2 No specific investigation is required. 
 

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workup and will be done especially for 
this research  
 
13.2 Disposables 
 
 
13.3 Implants  
 
13.4 Drugs / Contrast Media 
 
13.5 Others 
 
 
Who will bear the costs of the 
requirements which are not part of 
routine workup?      (mark  √ ) 
 
 
13.2 NA 
 
 
13.3 NA 
 
13.4 NA 
 
13.5 NA 
 
 
 
 
1.     Chief-guide/co-guides/student    
2.     Other Agencies (Name)________________________     
14. Participant Information Sheet 
      (mark  √  if yes) 
ü Attached English version 
ü Attached Odia version 
ü Certified that Odia version is a true translation of 
English version 
15. Participant Informed Consent Form 
      (mark  √  if yes) 
ü Attached English version 
ü Attached Odia version 

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ü Certified that Odia version is a true translation of 
English version 
16. Whether any work on this Protocol  
      has started or not?        
        (mark √ if yes, X if no)     
(Please enclose a separate certificate to this effect). 
 
17.Attached documents 
     (If any) 
 
17.1   Cover letter, through proper channel. 
17.2   Copy of the detailed Protocol is mandatory (vide Page 
6) 
17.3 Undertaking (vide Page 2) 
17.4 In case of multi-centric study, IEC clearance of other 
          centers must be provided 
17.5 Definite undertaking as to who will bear the 
         expenditure of injury related to the Protocol. 
17.6 In case an insurance cover is intended, Insurance 
         the certificate must be provided (as per ICMR 
guidelines) 
17.7 Permission as mentioned in Sl.No. 6.12, 8, 9 
17.8   In case of Clinical trials, proof of registration of 
          a clinical trial with ICMR needs to be submitted. 
17.9 Other relevant documents 
 
 
 
 
 

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THESIS PROTOCOL (MAIN DOCUMENT) 
 
 
Introduction 
 
 
 
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 (3). 
They usually result from trauma caused by the passage of hard stool and less commonly from 
diarrhoea also. The most common presenting symptom is pain, bleeding and secondary 
constipation. Most of the cases are managed conservatively by increased fluid intake, high fibre 
diet, sitz bath, stool softeners and topical application of sphincter relaxants(4).  
 
                     Constipation is one of the most common causes of anal fissure. Patients present the 
outpatient department with acute anal pain which is because of increased internal anal sphincter 
tone and also hard stool rubbing over the fissure.(3). Acute constipation and pain due to anal 
fissure is initially managed with lifestyle and dietary modifications like consuming adequate 
fluids, fibre diet and sitz bath(4).  
                     One of the fibrous supplements is isabgol husk which is a soluble fiber with 
enormous water absorbing property. Properties like nonirritant to the large bowel, non-

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fermenting and dichotomous stool normalizing agents make it one of the most preferred bulk-
forming agents(5). Low cost and over the counter availability are other plus points. Lactulose is 
also the most commonly prescribed laxative in anal fissures for constipation.  Polyethylene 
glycol is an osmotic laxative used in the treatment of anal fissures to relieve constipation.  
There have been 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. (6) (1)(2). 
However, there are no studies conducted on the efficacy of Polyethylene glycol vs isabgol husk 
and Lactulose in Acute fissure in ano.  However, studies say 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.(6).   
                              Patients in both arms are advised Anobliss (lidocaine with nifedipine) 
ointment for anal canal application to relieve anal spasms and acute pain. Patients in one arm are 
given polyethylene glycol for 2 weeks maximum and in the other arm, isabgol husk plus 
lactulose will be given for 2 weeks to improve the Bristol stool score and relieve from acute 
constipation. Patients will be assessed at 1 week and 1 month and evaluated for primary and 
secondary outcomes. 
 
 
Study objectives 
Primary objective 
• Time taken for the resolution of symptoms  
 
Secondary objectives 

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• Improvement in Bristol stool score 
• Healing of anal fissure at the end of one month 
• Adverse effects of PEG and lactulose with isabgol    
• Patient tolerance and compliance to the medications                        
 
 
 
Review of literature 
 
Keywords: Psyllium husk, PEG, Polyethylene glycol, fissure in ano, functional constipation, 
isabgol, constipation, lactulose Rome IV criteria, Bristol stool scale, laxatives, trials, Anal 
fissure, vas scale, nifedipine, anobliss. 
 
Search goal: To find studies which describe about efficacy of Polyethylene glycol and isobgol 
plus lactulose in acute fissure in ano. 
Strategy: Searches were made in the databases viz. Pubmed, google scholar, Indmed and various 
other journals that included Annals of surgery, World journal of surgery, The anatomical record, 
Surgical clinics of north America, Surgery (United States). The above-mentioned keywords and 
search goal were used. 
 
 
Materials and methods 
Study setting: 

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• 
OPD patients of department of General Surgery, All India Institute of Medical Sciences, 
Bhubaneswar 
Study design: 
• 
Primary purpose – Treatment 
Study type: 
• 
Randomised control study 
 Inclusion criteria: 
1. All those having acute fissure in ano between the age group of 18 to 75 yrs  
Exclusion criteria: 
1. Pregnancy / lactation 
2. Patients not giving consent 
3. Patients not able to understand the nature of the study 
4. Diabetes mellitus and chronic kidney disease 
5. Known intolerance to PEG/Lactulose or Isabgol 
6. Prior involvement in other study.  
7. Patient undergoing surgery for Fissure in Ano                             
Sample size: Sample size is 144, 72 in each group which is calculated using Kelsey, Fleiss 
corrected formula in the openepi.com. Based on a previous study on PEG vs isabgol.(2) 
 
Methods: 
• Recruitment: All patients aged more than 18 years of age presenting to the outpatient 
department of surgery department AIIMS Bhubaneshwar with complaints of acute fissure 
in ano will be assessed for recruitment in the study and will be randomly given 

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Polyethylene glycol (PEG) oral solution 15-30 ml once daily up to 2 weeks maximum, or 
isabgol husk 2 teaspoonfuls in 200 ml of warm water before bedtime plus lactulose syrup 
30 ml at bedtime for 2 weeks and assessed for primary and secondary outcomes. 
• Randomization: Random allocation software 
• Allocation concealment: Sealed envelope technique 
• Blinding: Single blinded study (Assessor) 
• Intervention: PEG and lactulose with isabgol 
• Follow up period: One week, 1 month  
 
 
 
 
 
 
 
 
 
 
Pain based on 
VAS score. 
Bristol stool 
form scale 
Healing of 
fissure 
Recurrence. 
0 visit 
 
 
 
NA 
NA 
1st visit 
 
 
NA 
NA 

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1 week 
 
2nd visit 
1st month 
 
 
 
 
NA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assessed for eligibility (n=144) 
Excluded (n=x) 
¨ Not meeting inclusion criteria (n=  ) 
¨ Declined to participate (n=  ) 
¨ Other reasons (n=  ) 
Lost to follow-up (give reasons) (n= ) 
Discontinued intervention (give reasons) (n= ) 
Allocated to PEG group (n= a/2) 
¨ Received allocated intervention (n=  ) 
¨ Did not receive allocated intervention (give 
reasons) (n=  ) 
Lost to follow-up (give reasons) (n=  ) 
Discontinued intervention (give reasons) (n=  ) 
Allocated to lactulose+isabgol group (n=a/2) 
¨ Received allocated intervention (n=  ) 
¨ Did not receive allocated intervention (give 
reasons) (n=  ) 
Allocation 
Follow-Up 
Randomized (a= 144-x) 
Enrollment 

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Statistical analysis plan:  
 
o Data will be entered in Microsoft excel, and analysis will be done using the latest 
version of IBM SPSS software. 
 
 
 
 
 
 
Ethical issues 
 
• 
Approval shall be taken from the Ethics Committee of the All India Institute of Medical 
Sciences, Bhubaneswar. 
• 
Informed written consent will be obtained from patient/patient attenders in their own 
understandable language. 
• 
A participant information sheet will be provided to the patients. 
• 
Participants will be explained that their identity will remain confidential. 

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Timelines 
 
 
 
ACTIVITY 
DEC’21 JAN’22 
MAR’22 
MAY’ 
22 
AUG’22-
JAN’23 
FEB’23-
JUL’23 
SEPT’ 
23 
OCT’23-
DEC’23 
PROTOCOL 
SUBMISSION 
 
 
 
 
 
 
 
ETHICS 
COMMITTEE 
 
 
 
 
 
 
 
START OF 
STUDY 
 
 
 
 
 
 
 
DATA 
COLLECTION 
 
 
 
 
 
 
 
DATA 
ANALYSIS 
 
 
 
 
 
 
 
PRESENTATION 
OF RESULTS 
 
 
 
 
 
 
 
 
 
 
 
References 
 
1.  
Lee-Robichaud H, Thomas K, Morgan J, Nelson RL. Lactulose versus Polyethylene 
Glycol for Chronic Constipation. The Cochrane database of systematic reviews [Internet]. 
2010 Jul 7 [cited 2021 Dec 31];(7). Available from: 
https://pubmed.ncbi.nlm.nih.gov/20614462/ 
2.  
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. Clinical drug 

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investigation [Internet]. 2004 [cited 2021 Dec 29];24(10):569–76. Available from: 
https://pubmed.ncbi.nlm.nih.gov/17523718/ 
3.  
Beaty JS, Shashidharan M. Anal Fissure. Clinics in Colon and Rectal Surgery [Internet]. 
2016 Mar 1 [cited 2021 Dec 28];29(1):30. Available from: /pmc/articles/PMC4755763/ 
4.  
Nelson RL, Thomas K, Morgan J, Jones A. Non surgical therapy for anal fissure. The 
Cochrane database of systematic reviews [Internet]. 2012 Feb 15 [cited 2021 Dec 
31];2012(2). Available from: https://pubmed.ncbi.nlm.nih.gov/22336789/ 
5.  
Garg MBBS MASCRS PM. PRACTICE APPLICATIONS Letters to the Editor Psyllium 
Husk Should Be Taken at a Higher Dose with Sufficient Water to Maximize Its Efficacy. 
2017 [cited 2021 Dec 24]; Available from: http://ees.elsevier.com/andjrnl 
6.  
Belsey JD, Geraint M, Dixon TA. Systematic review and meta-analysis: polyethylene 
glycol in adults with non-organic constipation. International journal of clinical practice 
[Internet]. 2010 Jun [cited 2021 Dec 31];64(7):944–55. Available from: 
https://pubmed.ncbi.nlm.nih.gov/20584228/ 
7.  
Psyllium and Alcohol/Food Interactions - Drugs.com [Internet]. [cited 2021 Dec 28]. 
Available from: https://www.drugs.com/food-interactions/psyllium.html