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

Chronic Anal Fissure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02527109
• Other study ID #: RDD 110
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: May 2016
• Est. completion date: August 22, 2018

Study information

• Verified date: June 2018
• Source: RDD Pharma Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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:

1. Treatment Group 1- 12 mg of Nifedipine to be self-administered twice daily.

2. 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.

3. 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:

1. 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

2. Experience symptoms of recurrence AND ARE

3. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 339
• Est. completion date: August 22, 2018
• Est. primary completion date: June 15, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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;

Related Conditions & MeSH terms

• Chronic Anal Fissure
• Fissure in Ano

Intervention

Drug:
• Nifedipine

Locations

Country	Name	City	State
Bulgaria	UMHAT "Sveti Georgi", Internal Consulting Department	Plovdiv
Bulgaria	"Multiprofile Hospital for Active Treatment - Doverie" AD, Clinic of Gastroenterology	Sofia
Bulgaria	II MHAT, Internal Clinic, Department of Gastroenterology	Sofia
Bulgaria	MC Health BG EOOD	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment Lulin	Sofia
Bulgaria	MC "New rehabilitation centre'' EOOD	Stara Zagora
Bulgaria	"Multiprofile Regional Hospital for Active Treatment - Dr. St. Cherkezov" AD Department of Gastroenterology	Veliko Tarnovo
Moldova, Republic of	IMSP Spitalul Clinic Municipal Nr 1	Chisinau
Moldova, Republic of	IMSP Spitalul Clinic Municipal Nr 3 "Sfanta Treime"	Chisinau
Moldova, Republic of	IMSP Spitalul Clinic Republican	Chisinau
Poland	Med-Gastr Centrum Medyczne	Lodz
Poland	Ambulatorium Medyczne Medical Hair & Esthetic	Lublin
Poland	Centrum Innowacyjnych Terapii Sp. z o.o. Oddzial w Piasecznie	Piaseczno
Poland	NZOZ Specjalistyczne Centrum Medyczne Flebo	Wolomin
Romania	Centrul Medical de Diagnostic si Tratament Ambulator Neomed SRL	Brasov
Romania	Centrul Medical Sfanta Vineri SRL	Bucharest
Romania	Institutul Clinic Fundeni	Bucharest
Romania	IRGH	Cluj Napoca	Jud. Cluj
Romania	Tvm Med Serv Srl	Cluj Napoca	Jud. Cluj
Romania	Institutul Regional de Gastroenterologie si Hepatologie "Prof. Dr. Octavian Fodor"	Cluj-Napoca	Jud. Cluj
Romania	Spit. Clinic Judetean de Urgenta "Sf. Apostol Andrei" Constanta	Constanta	Judet Constanta
Romania	Pelican Impex SRL	Oradea	Jud. Bihor
Romania	Dacmed SRL	Ploiesti	Judetul Prahova
Romania	SC Schnelbach Medical Care SRL	Ploiesti	Jud. Prahova

Sponsors (1)

Lead Sponsor	Collaborator
RDD Pharma Ltd

Countries where clinical trial is conducted

Bulgaria,  Moldova, Republic of,  Poland,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rectal pain and measured by VAS		measured at day 56
Secondary	Healing of anal fissure	Healing is defined by lack of pain AND evidence of epithelization in a physical examination	day 56