Cronic Anal fissure (CAF) The underlying pathogenesis of chronic anal fissure involves initial local trauma (generally caused by hard stools), resulting in a wound, internal anal sphincter spasm and reduced blood flow to the anal mucosa. The last two factors contribute to the appearance of an ulcer that does not heal, given that perfusion is inversely correlated with anal pressure. MedDRA version: 20.0 Level: LLT Classification code 10071195 Term: Chronic anal fissure System Organ Class: 10000
Conditions
Interventions
Trade Name: Anotrit
Product Name: Diltiazem 2% paste
Pharmaceutical Form: Cutaneous paste
INN or Proposed INN: Diltiazem Hydrochloride
CAS Number: 33286-22-5
Other descriptive name: DILTIAZEM HYDROCHL
Sponsors
Tecnimede, Sociedade Técnico-Medicinal, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients aged 18 years old or above; 2. Diagnosis of idiopathic chronic anal fissure unresponsive to previous therapy; 3. Patient able to comply with the study protocol as per investigator criteria; 4. Signed and dated informed consent by the patient or his/her representative/witness (as per applicable law); 5. Absence of any exclusion criterion Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 180 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Patient presenting with any of the clinical conditions mentioned below: a. Anal fissure lacking features for chronicity; b. Cured anal fissure; c. Infected chronic anal fissure; d. Multiple fissures; e. Fissure with irregular margins; f. Fissure at locations other than the midline; g. Fissure unassociated to sphincter spasm; 2. Patients with fecal incontinence, rectocele, rectal prolapse or fibrotic anal stenosis; 3. Patients with prior anal surgery; 4. Patients treated with botulinum toxin less than 6 months prior to enrolment; 5. Patients with chronic anal fissure secondary to other disorders such as chronic inflammatory bowel disease, intestinal tuberculosis, anal or peri-anal cancer, anal fistula, sexually transmitted diseases, anal or peri-anal sepsis; 6. Patients with malignant diseases and a life expectancy of less than 1 year or patients undergoing chemo- or radiotherapy less than 6 months prior to enrolment; 7. Patients with clinically significant cardiovascular disorder, namely New York Heart Association (NYHA) class III and IV heart failure, atrial fibrillation or atrial flutter caused by Wolff-Parkinson-White or Lown-Ganong-Levine syndromes, second and third degree atrioventricular block or sinoatrial node disease (except in the presence of a functioning artificial ventricular pacemaker), myocardial infarction with an ejection fraction below 0.40, ventricular tachycardia, severe bradycardia (lower than or equal to 40 beats per minute) or severe aortic stenosis.; 8. Patients with orthostatic (postural) hypotension or severe hypotension (systolic blood pressure below 90 mmHg); 9. Patients with respiratory insufficiency and need for long term oxygen therapy or home ventilation; 10. Patients with clinically significant renal failure; 11. Patients with known human immunodeficiency virus (HIV) infection; 12. Patients with known neuromuscular disease; 13. Pregnant or lactating patients; 14. Women of childbearing potential who are sexually active and who do not use an effective contraceptive method. 15. Patients with any changes in the previous 12 weeks to oral, sublingual, intravenous or intra-muscular therapy with vasodilators (beta blockers, nitrates, calcium antagonists, phosphodiesterase 4 inhibitors) or muscle relaxants (for example infusion of dantrolene); 16. Use of glyceryl trinitrate (GTN) ointment for 7 days (continuous or not) in the 4 weeks prior to signing the informed consent form (ICF). 17. Previous treatment with diltiazem hydrochloride cutaneous formulations or any other topical calcium channel blockers in the 8 weeks before randomization. 18. Patients who used an analgesic, anesthetic, cicatrizant, other topical vasodilators, corticosteroid, vitamins A or E, or any other active substances that might be active in anal mucosa regeneration, less than 3 days before. 19. History of hypersensitivity or intolerance to any of the investigational medicinal products, or to their active substances or excipients, or to similar drugs; 20. Patients with clotting disorders, unless the patients are taking anticoagulants drugs and the investigator considers that the International Normalized Ratio (INR) is adequate and stable; 21. Any known abnormal clinical or laboratory change that, as per the investigator, might interfere with the safety or efficacy assessment or any study procedure; 22. Patients who have participated in another clinical trial less than one month prior to enrolment or who are still involved in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of this clinical trial is to assess the relative efficacy (cure of chronic anal fissure) of the DTZ 2% cutaneous paste compared to placebo, in the treatment of chronic anal fissure (CAF), for up to 12 weeks (cure defined as complete closing evaluated through physical examination and re-epithelialization of the anal fissure observed in the anoscopy). ;Secondary Objective: Secondary objectives include the comparison between the two treatment arms of: a) cure rate within 8 weeks of treatment; b) cure rate within 4 weeks of treatment; c) improvement of symptoms triggered by defecation*) at 4, 8 and 12 weeks of treatment; d) tolerability within 12 weeks of treatment; e) assessment of CAF relapse rate during a 24-week follow-up period (for cured patients). * Pain triggered by defecation is considered the pain felt during and after defecation.;Primary end point(s): For the treatment part of the trial: - Proportion of patients for which CAF cure (defined as complete closing (anal fissure extension and depth equal to zero (0) mm) evaluated through physical examination and complete re-epithelialization of anal fissure observed in the anoscopy) was observed during the 12 week treatment period. ;Timepoint(s) of evaluation of this end point: For the double blind part of the trial: 12 weeks of treatment (V2, V3, and V4) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Proportion of patients for which cure of the CAF was observed until the 8th week of treatment (cured on visit 2 or 3 - V2 or V3); 2. Proportion of patients for which cure of the CAF was observed until the 4th week of treatment (cured on visit 2 - V2 ); 3. Symptomatic improvement of pain triggered by defecation vs. baseline assessed as variation in millimeters, using a visual analogue scale (VAS) for pain applied on the 12th week of treatment (visit 4 – V4); 4. Symptomatic improvement of pain triggered by defecation assessed as variation in millimeters, using a visual analogue scale (VAS) for pain applied on the 8th week of treatment (visit 3 – V3); 5. Symptomatic improvement of pain triggered by defecation assessed as variation in millimeters, using a visual analogue scale (VAS) for pain applied on the 4th week of treatment (visit 2 – V2); For the follow-up period: -For patients who complete the 24 week follow up phase, proportion of patients with fissure relapse during a 24-week follow up period after treatment withdrawal (final visit VF). Secondary safety endpoints: No. of adverse events (AE) reported for each treatment arm during the treatment phase; No. of serious and/or unexpected adverse reactions reported for each treatment arm during the treatment phase. ;Timepoint(s) of evaluation of this end point: 1 - Visit 2 and 3 - 8th week of treatment. 2- V2 - 4th week of treatment 3 - V4 - 12th week of treatment 4- V3 - 8th week of treatment 5- V2 - 4th week of treatment For follow-up period endpoint - Final visit Safety endpoints: total duration of the study. | — |
Countries
Czech Republic, Portugal, Spain
Contacts
Public ContactMedical Department
Tecnimede, Sociedade Técnico-Medicinal, S.A.
Outcome results
None listed