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

NCT06859554 | Completed Phase 4

• 1 other identifier: FGPC.1/12/2024
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

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

Conditions

Acute Anal Fissure; Anal Pain; Anorectal Disorders; Sphincter Spasm

Keywords

Anal fissure treatment; Glyceryl Trinitrate (GTN); Nifedipine ointment; Randomized controlled trial (RCT); Pain relief in anal fissures

Outcome Measures

Primary Outcomes (1)

• Healing Rate at 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 Outcomes (4)

• Change in Pain Scores (Visual Analog Scale [VAS])

  4 weeks

• Incidence and Severity of Adverse Effects

  4 weeks

• Patient Satisfaction with Treatment ( Self-validated Patient Satisfaction Score)

  4 weeks

• Time to Symptom Resolution

  4 weeks

Study Arms (4)

Arm 1: GTN 0.2%

ACTIVE COMPARATOR

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

Arm 2: GTN 0.4%

ACTIVE COMPARATOR

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

Arm 3: Nifedipine 0.2%

ACTIVE COMPARATOR

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

Arm 4: Nifedipine 0.5%

ACTIVE COMPARATOR

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

Interventions

Glyceryl Trinitrate (GTN) 0.2% Ointment DRUG

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.

Also known as: GTN 0.2%, Nitroglycerin 0.2% Ointment

Arm 1: GTN 0.2%

Glyceryl Trinitrate (GTN) 0.4% Ointment DRUG

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.

Also known as: GTN 0.4%, Nitroglycerin 0.4% Ointment

Arm 2: GTN 0.4%

Nifedipine 0.2% Ointment DRUG

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.

Also known as: Nifedipine Gel 0.2%, Nifedipine 0.2%

Arm 3: Nifedipine 0.2%

Nifedipine 0.5% Ointment DRUG

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.

Also known as: Nifedipine Gel 0.5%, Nifedipine 0.5%

Arm 4: Nifedipine 0.5%

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hafiz Muhammad Hamza: lead
• Federal Government Polyclinic (Postgraduate Medical Institute): collaborator

Study Sites (1)

Federal Government Polyclinic (Postgraduate Medical Institute)

Islamabad, Capital, 051, Pakistan

Location

Related Publications (4)

• Mustafa NA, Cengiz S, Turkyilmaz S, Yucel Y. Comparison of topical glyceryl trinitrate ointment and oral nifedipine in the treatment of chronic anal fissure. Acta Chir Belg. 2006 Jan-Feb;106(1):55-8. doi: 10.1080/00015458.2006.11679834.

  PMID: 16612915 BACKGROUND

• Wang C, Ni J, Xiong Y, Chen J, Li B, Xu L. The efficacy of diltiazem, glyceryl trinitrate, nifedipine, minoxidil, and lidocaine for the medical management of anal fissure: a systematic review and network meta-analysis of randomized controlled trials. Int J Surg. 2025 Apr 1;111(4):3020-3029. doi: 10.1097/JS9.0000000000002263.

  PMID: 39878173 BACKGROUND

• Momayez Sanat Z, Mohammadi Ganjaroudi N, Mansouri M. The Effect of Topical Nifedipine versus Diltiazem on the Acute Anal Fissure: A Randomized Clinical Trial. Middle East J Dig Dis. 2023 Apr;15(2):121-125. doi: 10.34172/mejdd.2023.330. Epub 2023 Apr 30.

  PMID: 37546514 BACKGROUND

• Shrestha SK, Thapa PB, Maharjan DK, Tamang TY. Effectiveness of 0.2% Glyceryl Trinitrate and 0.5% Nifedipine in the Treatment of Chronic Anal Fissure. JNMA J Nepal Med Assoc. 2017 Jan-Mar;56(205):149-152.

  PMID: 28598453 BACKGROUND

Related Links

• Comparative Study of 0.2%GlycerylTrinitrate Ointment versus LateralInternal Sphincterotomy for Chronic Anal Fissure
• FDA Approves GTN for Chronic Anal Fissure Pain
• Nifedipine 0.2% ointment is a topical calcium channel blocker used for anal fissure treatment, including in diabetic patients, by relaxing the anal sphincter and increasing blood flow. It is compounded with white petrolatum and has a USP beyond-use date

MeSH Terms

Conditions

Rectal Diseases

Interventions

Nitroglycerin; Ointments; Nifedipine

Condition Hierarchy (Ancestors)

Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Nitro Compounds; Organic Chemicals; Dosage Forms; Pharmaceutical Preparations; Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Naveed Ullah Khan, Consultant surgery, HOD

  Federal Government Polyclinic (Postgraduate Medical Institute)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants do not know which specific treatment they are receiving, and investigators assessing outcomes are also blinded. However, care providers and data analysts are aware of group assignments.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: House Officer, Foundation University School of Health Sciences

Model Details: This is a randomized, double-blind, parallel-arm clinical trial evaluating the efficacy and safety of GTN (0.2% and 0.4%) versus Nifedipine (0.2% and 0.5%) in the treatment of acute anal fissures.

Study Record Dates

• First Submitted: February 28, 2025
• First Posted: March 5, 2025
• Study Start: March 17, 2025
• Primary Completion: May 10, 2025
• Study Completion: May 10, 2025
• Last Updated: May 14, 2025

Record last verified: 2025-02

Locations

PA (1)