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

May 11, 2025 updated by: Hafiz Muhammad Hamza

Assessing the Therapeutic Efficacy and Safety Profile of Glyceryl Trinitrate (GTN) and Nifedipine Ointments in Acute Anal Fissure Treatment: A Parallel-arm Clinical Trial

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

110

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Pakistan
    • Capital
      • Islamabad, Capital, Pakistan, 051
        • Federal Government Polyclinic (Postgraduate Medical Institute)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm 1: GTN 0.2%
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.
Drug: Glyceryl Trinitrate (GTN) 0.2% Ointment
Participants will apply 0.2% Glyceryl Trinitrate (GTN) ointment to the anal region twice daily for four weeks. GTN functions as a nitric oxide donor, reducing internal anal sphincter tone to improve blood flow and promote fissure healing. The study aims to assess its effectiveness in symptom relief, fissure healing, and associated side effects such as headaches and dizziness.
Other Names:
  • GTN 0.2%
  • Nitroglycerin 0.2% Ointment
Active Comparator: Arm 2: GTN 0.4%
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
Drug: Glyceryl Trinitrate (GTN) 0.4% Ointment
Participants will apply 0.4% Glyceryl Trinitrate (GTN) ointment twice daily for four weeks. This increased concentration aims to determine dose-dependent efficacy and adverse effects in treating acute anal fissures. GTN acts by relaxing smooth muscle, decreasing sphincter tone, and enhancing mucosal blood flow to promote healing.
Other Names:
  • GTN 0.4%
  • Nitroglycerin 0.4% Ointment
Active Comparator: Arm 3: Nifedipine 0.2%
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.
Drug: Nifedipine 0.2% Ointment
Participants will apply 0.2% Nifedipine ointment twice daily for four weeks. Nifedipine, a calcium channel blocker, reduces sphincter tone by inhibiting calcium influx into smooth muscle cells, leading to improved fissure healing. This arm will assess its effectiveness in symptom relief and healing rates, with a focus on side effects such as local irritation or hypotension.
Other Names:
  • Nifedipine Gel 0.2%
  • Nifedipine 0.2%
Active Comparator: Arm 4: Nifedipine 0.5%
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.
Drug: Nifedipine 0.5% Ointment
Participants will apply 0.5% Nifedipine ointment twice daily for four weeks. This higher concentration is used to evaluate whether increased potency provides superior symptom resolution and healing rates compared to 0.2% Nifedipine. The study will also assess any potential adverse effects, including local irritation, dizziness, and hypotension.
Other Names:
  • Nifedipine Gel 0.5%
  • Nifedipine 0.5%

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Healing Rate at 4 Weeks
Time Frame: 4 weeks
The proportion of participants achieving complete epithelialization of the anal fissure on clinical examination at the end of four weeks.
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and Severity of Adverse Effects
Time Frame: 4 weeks
Assessment of drug-related side effects, including headache, dizziness, local irritation, and hypotension, recorded throughout the study duration.
4 weeks
Time to Symptom Resolution
Time Frame: 4 weeks
Duration until complete resolution of pain and cessation of rectal bleeding.
4 weeks
Change in Pain Scores (Visual Analog Scale [VAS])
Time Frame: 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.
4 weeks
Patient Satisfaction with Treatment ( Self-validated Patient Satisfaction Score)
Time Frame: 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.
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hafiz Muhammad Hamza

Collaborators

Federal Government Polyclinic (Postgraduate Medical Institute)

Investigators

  • Study Chair: Naveed Ullah Khan, Consultant surgery, HOD, Federal Government Polyclinic (Postgraduate Medical Institute)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 17, 2025

Primary Completion (Actual)

May 10, 2025

Study Completion (Actual)

May 10, 2025

Study Registration Dates

First Submitted

February 28, 2025

First Submitted That Met QC Criteria

February 28, 2025

First Posted (Actual)

March 5, 2025

Study Record Updates

Last Update Posted (Actual)

May 14, 2025

Last Update Submitted That Met QC Criteria

May 11, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FGPC.1/12/2024

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

At this stage, no final decision has been made regarding the sharing of individual participant data (IPD). Data sharing will be considered based on future research needs, ethical guidelines, and institutional policies. Any decision to share IPD will be made in compliance with data protection regulations and patient confidentiality standards.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Acute Anal Fissure

Clinical Trials on Glyceryl Trinitrate (GTN) 0.2% Ointment

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Sri Lanka

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe