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The Effect of Intra-anal Nifedipine, Used As Add-on to Conservative Therapy, on Pain in Patients With Anal Fissure

Primary Purpose

Chronic Anal Fissure

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Nifedipine
Sponsored by
RDD Pharma Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Anal Fissure

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

- Subjects meeting the following criteria will be eligible to participate in the trial:

  1. Single anal fissure;
  2. Signed written informed consent;
  3. Male or female subjects 18 to 65 years of age inclusive;
  4. Has chronic anal fissure defined as history of rectal pain at least three days a week for at least 6 weeks - or more AND at least one of the following:

    • Sentinel skin tag
    • Hypertrophied anal papilla
    • Exposure of the underlying internal anal sphincter
    • Anal cicatrisation
  5. Visual analogue scale of average 24 hours rectal pain (VAS) of > 40 mm in screening visit
  6. Capable of using the IVRS and able to adequately communicate comprehension of the IVRS questions to the investigator
  7. If female, is non-lactating, has a negative urine pregnancy test result, and does not plan on becoming pregnant during the study, or not of childbearing potential (hysterectomy or tubal ligation at least 6 months prior to entry to the study or post-menopausal for 1 year); if of childbearing potential (including peri-menopausal women who have had a menstrual period within one year) must practice or be willing to continue to practice acceptable birth control from screening and until 1 week after the study medication has been discontinued.

Acceptable birth control includes :

  • combined (estrogen and progestogen containing) hormonal contraception
  • associated with inhibition of ovulation; oral OR intravaginal OR transdermal.
  • progestogen-only hormonal contraception associated with inhibition of ovulation: oral OR injectable OR implantable.
  • progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action
  • intrauterine device (IUD)
  • intrauterine hormone-releasing system ( IUS)
  • bilateral tubal occlusion
  • vasectomised partner
  • sexual abstinence
  • male or female condom with or without spermicide
  • cap, diaphragm or sponge with spermicide

Exclusion Criteria:

  • Subjects are excluded from participation in the study if any of the following criteria apply:

    1. Known allergy to Nifedipine
    2. Unwilling to stop all other concomitant topical preparations applied in and around the anus from screening through the end of the study
    3. Subfissure injection of botulinum toxin in the 3 months prior to screening.
    4. Fissure resulting from inflammatory bowel disease, venereal disease, perianal psoriasis, immunodeficiency syndrome
    5. Atypical fissure (occurs off the midline) in which secondary causes were not excluded.
    6. Deemed by the investigator as anal fissure for which surgery is indicated
    7. Anal abscess;
    8. Grade 4 hemorrhoids
    9. Fixed anal stenosis
    10. Active or past history of cardiovascular or cerebrovascular disease including but not limited to angina pectoris, myocardial infarction, transient ischemic attacks/stroke, arrhythmia or ecg changes that requires medical treatment or deemed by the investigator as clinically significant, moderate to severe congestive heart failure, or cardiac valve abnormalities;
    11. Type 1 diabetes mellitus
    12. Insulin treated type 2 diabetes mellitus
    13. Renal failure defined as a serum creatinine > 1.5 mg/dL (133 µmol/L) at screening
    14. Liver disease defined as Aspartate aminotransferase (AST) or alanine aminotransferase(ALT) >2 X upper limit of normal at screening
    15. Malignant disease within 3 years of screening
    16. Has uncontrolled hypertension (sitting blood pressure >160/95 mmHg at screening)
    17. Has hypotension (blood pressure lower than 90/60 mm Hg at screening)
    18. History of chronic gastrointestinal disease such as Crohn's disease or ulcerative colitis
    19. History of major rectal surgery
    20. History of HIV, Hepatitis B, Hepatitis C
    21. Has clinical laboratory test values (chemistry, hematology, or urinalysis) judged to be clinically significant by the investigator at screening;
    22. Has used, in the last two weeks, drugs that may affect blood coagulation, such as Aspirin at a dose higher than 500 mg/day, Warfarin, Sintrom, Enoxaparin, Nadroparin, Heparin, Clopidogrel, Ticlopidine Rivaroxaban, Apixaban, Edoxaban
    23. Is treated with drugs that may affect the anal sphincter:

      1. Calcium channel blockers such as Nifedipine, Diltiazem or Verapamil
      2. Nitroglycerin or nitrates
    24. Has, upon physical examination, a rectal deformation or signs of rectal disease such as fistula, infection or space occupying lesion;
    25. Participated in a clinical study in the last 30 days prior to screening.
    26. Is an immediate family member of personnel directly affiliated with the study at the investigative site, or is personally directly affiliated with the study at the investigative site; or is employed or related to the Sponsor, CRO or investigator;

Sites / Locations

  • UMHAT "Sveti Georgi", Internal Consulting Department
  • "Multiprofile Hospital for Active Treatment - Doverie" AD, Clinic of Gastroenterology
  • II MHAT, Internal Clinic, Department of Gastroenterology
  • MC Health BG EOOD
  • Multiprofile Hospital for Active Treatment Lulin
  • MC "New rehabilitation centre'' EOOD
  • "Multiprofile Regional Hospital for Active Treatment - Dr. St. Cherkezov" AD Department of Gastroenterology
  • IMSP Spitalul Clinic Municipal Nr 1
  • IMSP Spitalul Clinic Municipal Nr 3 "Sfanta Treime"
  • IMSP Spitalul Clinic Republican
  • Med-Gastr Centrum Medyczne
  • Ambulatorium Medyczne Medical Hair & Esthetic
  • Centrum Innowacyjnych Terapii Sp. z o.o. Oddział w Piasecznie
  • NZOZ Specjalistyczne Centrum Medyczne Flebo
  • Pelican Impex SRL
  • IRGH
  • Tvm Med Serv Srl
  • Institutul Regional de Gastroenterologie si Hepatologie "Prof. Dr. Octavian Fodor"
  • SC Schnelbach Medical Care SRL
  • Spit. Clinic Judetean de Urgenta "Sf. Apostol Andrei" Constanta
  • Dacmed SRL
  • Centrul Medical de Diagnostic si Tratament Ambulator Neomed SRL
  • Institutul Clinic Fundeni
  • Centrul Medical Sfanta Vineri SRL

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Experimental

Arm Label

Placebo

Nifedipine 12 mg/day

Nifedipine 24 mg/day

Arm Description

Intra-anal placebo administered BID.

Intra-anal Nifedipine 12 mg administered OD.

Intra-anal Nifedipine 12 mg administered BID.

Outcomes

Primary Outcome Measures

Rectal pain and measured by VAS

Secondary Outcome Measures

Healing of anal fissure
Healing is defined by lack of pain AND evidence of epithelization in a physical examination

Full Information

First Posted
August 10, 2015
Last Updated
October 21, 2018
Sponsor
RDD Pharma Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT02527109
Brief Title
The Effect of Intra-anal Nifedipine, Used As Add-on to Conservative Therapy, on Pain in Patients With Anal Fissure
Official Title
The Effect of Intra-anal Nifedipine, Used As Add-on to Conservative Therapy, on Pain in Patients With Anal Fissure
Study Type
Interventional

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
May 2016 (undefined)
Primary Completion Date
June 15, 2018 (Actual)
Study Completion Date
August 22, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
RDD Pharma Ltd

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The objective of the study is to examine the effect of Nifedipine, applied intra-anally through our drug delivery device, on rectal pain severity in anal fissure patients that are being managed with conservative treatment.
Detailed Description
This is a randomized, double-blinded study. All patients in the study will be treated with the conservative standard of care for anal fissure. Study medication will be used as an add-on to conservative therapy, and will consist of 3 groups: Treatment Group 1- 12 mg of Nifedipine to be self-administered twice daily. Treatment Group 2- 12 mg of Nifedipine to be self-administered once daily in the morning hours and placebo to be self-administered in the evening. Placebo Group - Placebo to be self-administered twice daily. Approximately 330 subjects will participate in this study. A screening visit will be used to determine subject suitability for inclusion in the trial. Within one week of the screening visit, subjects who meet all inclusion criteria and none of the exclusion criteria will receive either Nifedipine 12 mg X2 a day (BID) (24 mg/day total) or Nifedipine 12 mg X1/day to be administered in the morning hours and a matching placebo X1/day to be administered in the evening hours (12 mg/day total) or a matching placebo X2 a day (BID) (0 mg/day total) for a period of 8 weeks. During this period, 4 study visits (at 0, 2, 5, and 8 weeks) will take place. Study medication and placebo will be administered BID (in the morning and in the evening). In addition to receiving study medication, subjects will be maintained on a conservative standard treatment for Anal Fissure: sitz baths, high fiber diet, stool softeners and plenty of fluids. Upon completion of the treatment cycle, patients will be contacted by phone (at weeks 10, 13 and 16) and will be questioned about recurrent symptoms e.g. pain or bleeding. Patients that: Were enrolled to one of the investigational groups ,and completed the 8 weeks treatment period or discontinued treatment because the investigator deemed them as healed AND Experience symptoms of recurrence AND ARE Willing to participate in an open label extension will receive Nifedipine 12 mg X2 a day (BID) for a period of 8 weeks. During this period, 4 study visits (at 0, 2, 5, and 8 weeks from the start of retreatment) will take place.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Anal Fissure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
339 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Intra-anal placebo administered BID.
Arm Title
Nifedipine 12 mg/day
Arm Type
Experimental
Arm Description
Intra-anal Nifedipine 12 mg administered OD.
Arm Title
Nifedipine 24 mg/day
Arm Type
Experimental
Arm Description
Intra-anal Nifedipine 12 mg administered BID.
Intervention Type
Drug
Intervention Name(s)
Nifedipine
Primary Outcome Measure Information:
Title
Rectal pain and measured by VAS
Time Frame
measured at day 56
Secondary Outcome Measure Information:
Title
Healing of anal fissure
Description
Healing is defined by lack of pain AND evidence of epithelization in a physical examination
Time Frame
day 56

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: - Subjects meeting the following criteria will be eligible to participate in the trial: Single anal fissure; Signed written informed consent; Male or female subjects 18 to 65 years of age inclusive; Has chronic anal fissure defined as history of rectal pain at least three days a week for at least 6 weeks - or more AND at least one of the following: Sentinel skin tag Hypertrophied anal papilla Exposure of the underlying internal anal sphincter Anal cicatrisation Visual analogue scale of average 24 hours rectal pain (VAS) of > 40 mm in screening visit Capable of using the IVRS and able to adequately communicate comprehension of the IVRS questions to the investigator If female, is non-lactating, has a negative urine pregnancy test result, and does not plan on becoming pregnant during the study, or not of childbearing potential (hysterectomy or tubal ligation at least 6 months prior to entry to the study or post-menopausal for 1 year); if of childbearing potential (including peri-menopausal women who have had a menstrual period within one year) must practice or be willing to continue to practice acceptable birth control from screening and until 1 week after the study medication has been discontinued. Acceptable birth control includes : combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation; oral OR intravaginal OR transdermal. progestogen-only hormonal contraception associated with inhibition of ovulation: oral OR injectable OR implantable. progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action intrauterine device (IUD) intrauterine hormone-releasing system ( IUS) bilateral tubal occlusion vasectomised partner sexual abstinence male or female condom with or without spermicide cap, diaphragm or sponge with spermicide Exclusion Criteria: Subjects are excluded from participation in the study if any of the following criteria apply: Known allergy to Nifedipine Unwilling to stop all other concomitant topical preparations applied in and around the anus from screening through the end of the study Subfissure injection of botulinum toxin in the 3 months prior to screening. Fissure resulting from inflammatory bowel disease, venereal disease, perianal psoriasis, immunodeficiency syndrome Atypical fissure (occurs off the midline) in which secondary causes were not excluded. Deemed by the investigator as anal fissure for which surgery is indicated Anal abscess; Grade 4 hemorrhoids Fixed anal stenosis Active or past history of cardiovascular or cerebrovascular disease including but not limited to angina pectoris, myocardial infarction, transient ischemic attacks/stroke, arrhythmia or ecg changes that requires medical treatment or deemed by the investigator as clinically significant, moderate to severe congestive heart failure, or cardiac valve abnormalities; Type 1 diabetes mellitus Insulin treated type 2 diabetes mellitus Renal failure defined as a serum creatinine > 1.5 mg/dL (133 µmol/L) at screening Liver disease defined as Aspartate aminotransferase (AST) or alanine aminotransferase(ALT) >2 X upper limit of normal at screening Malignant disease within 3 years of screening Has uncontrolled hypertension (sitting blood pressure >160/95 mmHg at screening) Has hypotension (blood pressure lower than 90/60 mm Hg at screening) History of chronic gastrointestinal disease such as Crohn's disease or ulcerative colitis History of major rectal surgery History of HIV, Hepatitis B, Hepatitis C Has clinical laboratory test values (chemistry, hematology, or urinalysis) judged to be clinically significant by the investigator at screening; Has used, in the last two weeks, drugs that may affect blood coagulation, such as Aspirin at a dose higher than 500 mg/day, Warfarin, Sintrom, Enoxaparin, Nadroparin, Heparin, Clopidogrel, Ticlopidine Rivaroxaban, Apixaban, Edoxaban Is treated with drugs that may affect the anal sphincter: Calcium channel blockers such as Nifedipine, Diltiazem or Verapamil Nitroglycerin or nitrates Has, upon physical examination, a rectal deformation or signs of rectal disease such as fistula, infection or space occupying lesion; Participated in a clinical study in the last 30 days prior to screening. Is an immediate family member of personnel directly affiliated with the study at the investigative site, or is personally directly affiliated with the study at the investigative site; or is employed or related to the Sponsor, CRO or investigator;
Facility Information:
Facility Name
UMHAT "Sveti Georgi", Internal Consulting Department
City
Plovdiv
Country
Bulgaria
Facility Name
"Multiprofile Hospital for Active Treatment - Doverie" AD, Clinic of Gastroenterology
City
Sofia
ZIP/Postal Code
1632
Country
Bulgaria
Facility Name
II MHAT, Internal Clinic, Department of Gastroenterology
City
Sofia
Country
Bulgaria
Facility Name
MC Health BG EOOD
City
Sofia
Country
Bulgaria
Facility Name
Multiprofile Hospital for Active Treatment Lulin
City
Sofia
Country
Bulgaria
Facility Name
MC "New rehabilitation centre'' EOOD
City
Stara Zagora
Country
Bulgaria
Facility Name
"Multiprofile Regional Hospital for Active Treatment - Dr. St. Cherkezov" AD Department of Gastroenterology
City
Veliko Tarnovo
ZIP/Postal Code
5002
Country
Bulgaria
Facility Name
IMSP Spitalul Clinic Municipal Nr 1
City
Chisinau
Country
Moldova, Republic of
Facility Name
IMSP Spitalul Clinic Municipal Nr 3 "Sfanta Treime"
City
Chisinau
Country
Moldova, Republic of
Facility Name
IMSP Spitalul Clinic Republican
City
Chisinau
Country
Moldova, Republic of
Facility Name
Med-Gastr Centrum Medyczne
City
Lodz
ZIP/Postal Code
91-034
Country
Poland
Facility Name
Ambulatorium Medyczne Medical Hair & Esthetic
City
Lublin
ZIP/Postal Code
20-844
Country
Poland
Facility Name
Centrum Innowacyjnych Terapii Sp. z o.o. Oddział w Piasecznie
City
Piaseczno
ZIP/Postal Code
05-500
Country
Poland
Facility Name
NZOZ Specjalistyczne Centrum Medyczne Flebo
City
Wolomin
ZIP/Postal Code
05-200
Country
Poland
Facility Name
Pelican Impex SRL
City
Oradea
State/Province
Jud. Bihor
ZIP/Postal Code
410469
Country
Romania
Facility Name
IRGH
City
Cluj Napoca
State/Province
Jud. Cluj
ZIP/Postal Code
400162
Country
Romania
Facility Name
Tvm Med Serv Srl
City
Cluj Napoca
State/Province
Jud. Cluj
Country
Romania
Facility Name
Institutul Regional de Gastroenterologie si Hepatologie "Prof. Dr. Octavian Fodor"
City
Cluj-Napoca
State/Province
Jud. Cluj
ZIP/Postal Code
400162
Country
Romania
Facility Name
SC Schnelbach Medical Care SRL
City
Ploiesti
State/Province
Jud. Prahova
Country
Romania
Facility Name
Spit. Clinic Judetean de Urgenta "Sf. Apostol Andrei" Constanta
City
Constanta
State/Province
Judet Constanta
Country
Romania
Facility Name
Dacmed SRL
City
Ploiesti
State/Province
Judetul Prahova
Country
Romania
Facility Name
Centrul Medical de Diagnostic si Tratament Ambulator Neomed SRL
City
Brasov
ZIP/Postal Code
500283
Country
Romania
Facility Name
Institutul Clinic Fundeni
City
Bucharest
ZIP/Postal Code
022328
Country
Romania
Facility Name
Centrul Medical Sfanta Vineri SRL
City
Bucharest
Country
Romania

12. IPD Sharing Statement

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The Effect of Intra-anal Nifedipine, Used As Add-on to Conservative Therapy, on Pain in Patients With Anal Fissure

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