Efficacy and Safety of GTN vs. Nifedipine in Acute Anal Fissure: A Clinical Trial

Phase 4

Completed

• Conditions: Acute Anal Fissure; Anal Pain; Anorectal Disorders; Sphincter Spasm
• Interventions: Drug: Glyceryl Trinitrate (GTN) 0.2% Ointment; Drug: Glyceryl Trinitrate (GTN) 0.4% Ointment; Drug: Nifedipine 0.2% Ointment; Drug: Nifedipine 0.5% Ointment

• Registration Number: NCT06859554
• Lead Sponsor: Hafiz Muhammad Hamza

Brief Summary

The goal of this clinical trial is to compare the therapeutic efficacy and safety profile of Glyceryl Trinitrate (GTN) and Nifedipine ointments in the treatment of acute anal fissures in adults. The main questions it aims to answer are:

Which ointment is more effective in promoting fissure healing and symptom relief? What are the adverse effects associated with each treatment? Researchers will compare GTN and Nifedipine ointments to determine which provides better symptom resolution with fewer side effects.

Participants will:

Apply GTN or Nifedipine ointment topically twice daily for four weeks Attend follow-up visits for symptom assessment and adverse effect monitoring

Detailed Description

Background and Rationale:

Anal fissures are painful linear tears in the anoderm, commonly caused by trauma from hard stool passage, leading to increased internal anal sphincter tone and ischemia. Acute fissures typically heal within six to eight weeks, while chronic fissures persist beyond this period. First-line treatment includes non-surgical options such as topical pharmacotherapy to reduce sphincter spasm and improve mucosal blood flow.

Glyceryl Trinitrate (GTN) and Nifedipine are widely used topical agents for anal fissure management. GTN acts as a nitric oxide donor, reducing sphincter tone via smooth muscle relaxation, though it is often associated with headaches. Nifedipine, a calcium channel blocker, lowers sphincter tone by inhibiting calcium influx into smooth muscle cells and has a more favorable side effect profile. Despite their widespread use, their comparative efficacy and safety remain a subject of debate.

This randomized controlled trial (RCT) aims to compare GTN and Nifedipine ointments in acute anal fissure treatment, evaluating symptom resolution, healing rates, and adverse effects to determine the optimal therapeutic choice.

Study Overview:

This double-blind, randomized, parallel-arm clinical trial will compare GTN and Nifedipine in patients with acute anal fissures. Participants will be allocated into:

GTN Group: Receiving either 0.2% or 0.4% GTN ointment, applied twice daily for four weeks.

Nifedipine Group: Receiving either 0.2% or 0.5% Nifedipine ointment, applied twice daily for four weeks.

The primary outcome is healing rate at four weeks, with secondary outcomes including pain reduction, side effects, patient satisfaction, and recurrence rates over six months.

Data Analysis:

Collected data will undergo statistical analysis using Chi-square tests, ANOVA, Kaplan-Meier survival analysis, and logistic regression modeling to identify treatment effectiveness and predictors of success.

Ethical Considerations:

The study is approved by the Federal Government Polyclinic Ethics Review Board, with written informed consent obtained from participants. All procedures comply with Good Clinical Practice (GCP) guidelines, and data confidentiality will be strictly maintained.

Expected Impact:

This study aims to refine treatment protocols for acute anal fissures, offering evidence-based guidance on the most effective and safest medical therapy, potentially reducing the need for surgical intervention.

Study Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-28
• Study First Submitted QC: 2025-02-28
• Study First Posted: 2025-03-05
• Study Start: 2025-03-17
• Primary Completion: 2025-05-10
• Study Completion: 2025-05-10
• Last Update Submitted: 2025-05-11
• Last Update Posted: 2025-05-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 110

Inclusion Criteria

• Participants must meet all of the following criteria to be eligible for the study:
• Age 18 to 65 years (to exclude elderly patients with different treatment responses).
• Diagnosis of acute anal fissure based on clinical examination (symptom duration ≤6 weeks).
• Willingness to participate in the study and provide written informed consent.
• Availability for follow-up visits during the study period.
• No prior use of GTN or Nifedipine for anal fissure within the past one month.
• Presence of at least one of following symptoms: Anal pain, Bleeding during or after defecation and Difficulty in defecation

Exclusion Criteria

• Participants will be excluded if they meet any of the following criteria:
• History of chronic anal fissure (>6 weeks duration) or prior anal fissure treatment within the past month.
• Pregnant or breastfeeding women.
• Known allergy or hypersensitivity to Glyceryl Trinitrate (GTN) or Nifedipine ointments.
• History of cardiovascular diseases or contraindications to GTN or Nifedipine (e.g., hypotension, severe heart disease).
• Presence of severe systemic diseases (e.g., uncontrolled diabetes, renal failure, autoimmune disorders) or conditions that may affect wound healing or medication tolerance.
• Use of other topical treatments for anal fissure within the past month.
• Secondary anal fissures associated with conditions e.g crohn's disease, tuberculosis, syphilis, HIV and other systemic diseases
• Previous anal surgery (including lateral internal sphincterotomy).
• History of recurrent anal fissures (>2 previous episodes in the past year).
• Inability to comply with study requirements or follow-up visits.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1: GTN 0.2%	Glyceryl Trinitrate (GTN) 0.2% Ointment	Participants in this arm will apply 0.2% Glyceryl Trinitrate (GTN) ointment twice daily for four weeks. The primary goal is to assess its efficacy in healing acute anal fissures and symptom relief while monitoring for side effects such as headaches and dizziness.
Arm 2: GTN 0.4%	Glyceryl Trinitrate (GTN) 0.4% Ointment	Participants in this arm will apply 0.4% Glyceryl Trinitrate (GTN) ointment twice daily for four weeks. This higher concentration aims to determine the dose-dependent efficacy and side effect profile compared to 0.2% GTN
Arm 3: Nifedipine 0.2%	Nifedipine 0.2% Ointment	Participants in this arm will apply 0.2% Nifedipine ointment twice daily for four weeks. The study will evaluate its effectiveness in fissure healing, pain relief, and incidence of adverse effects such as local irritation or hypotension.
Arm 4: Nifedipine 0.5%	Nifedipine 0.5% Ointment	Participants in this arm will apply 0.5% Nifedipine ointment twice daily for four weeks. This higher concentration will assess whether increased potency provides superior symptom resolution and healing rates while monitoring potential side effects.

Primary Outcome Measures

Name	Time	Method
Healing Rate at 4 Weeks	4 weeks	The proportion of participants achieving complete epithelialization of the anal fissure on clinical examination at the end of four weeks.

Secondary Outcome Measures

Name	Time	Method
Change in Pain Scores (Visual Analog Scale [VAS])	4 weeks	Reduction in pain scores from baseline to post-treatment, measured using the Visual Analog Scale (VAS), a 10-point scale ranging from 0 (no pain) to 10 (worst possible pain). Higher scores indicate greater pain severity.
Incidence and Severity of Adverse Effects	4 weeks	Assessment of drug-related side effects, including headache, dizziness, local irritation, and hypotension, recorded throughout the study duration.
Patient Satisfaction with Treatment ( Self-validated Patient Satisfaction Score)	4 weeks	Evaluation of patient-reported satisfaction with treatment outcomes, assessed using a structured questionnaire.; Scoring System: Patient satisfaction is assessed using the Self-validated Patient Satisfaction Score, with responses recorded on a 5-point Likert scale. The scoring system is as follows: * Very satisfied = 5; * Somewhat satisfied = 4; * Neutral = 3; * Somewhat dissatisfied = 2; * Very dissatisfied = 1; * Higher scores indicate greater patient satisfaction with treatment outcomes.
Time to Symptom Resolution	4 weeks	Duration until complete resolution of pain and cessation of rectal bleeding.

Trial Locations

Locations (1)

Federal Government Polyclinic (Postgraduate Medical Institute); 🇵🇰 Islamabad, Capital, Pakistan