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

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.

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.