Procitits
Conditions
Interventions
Group A receives tacrolimus suppositories 2 mg for 28 days.
Group B receives beclomethason suppositories 3 mg for 28 days.
Sponsors
Erasmus MC, Universitair Medisch Centrum Rotterdam
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Endoscopically or histologically proven ulcerative proctitis at least 3 months before randomization. Proctitis is defined as: disease activity to 20 cm beyond the anal verge. Refractory proctitis defined as a failure to at least the use of 5-asa suppositories of a maximum of 1 gram for at least 21 days and recurrent proctitis is defined as relapse within 3 months after stopping of local adequate 5-asa treatment. Endoscopy may have been performed up to 3 weeks before screening, if the endoscopy was well documented and biopsies were taken. Age: 18-70 years and written informed consent. Permitted concomitant therapy: oral aminosalicylates, azathioprine, 6-mercatopurine and methotrexate at stable dose for 12 weeks.
Exclusion criteria
Exclusion criteria: Use of enemas within 14 days prior to randomization Treatment with tacrolimus prior to randomization Treatment with any investigational drug in another trial within 12 weeks of randomization Treatment with any form of corticosteroids within 4 weeks of randomization Abnormal renal function (eGFR 2 ULN). Other significant medical illness that might interfere with this study: Current malignancy, immunodeficiency syndromes. Any known pre-existing medical condition that could interfere with the patient's participation in and completion of the study such as: - Pre-existing psychiatric condition, especially depression, or a history of severe psychiatric disorder, such as major psychoses, suicidal ideation and/or suicidal attempt are excluded. Severe depression would include the following: (a) subjects who have been hospitalized for depression, (b) subjects who have received electroconvulsive therapy for depression, or (c) subjects whose depression has resulted in a prolonged absence of work and/or significant disruption of daily functions. Subjects with a history of mild depression may be considered for entry into the protocol provided that a pretreatment assessment of the subject*s mental status supports that the subject is clinically stable and that there is ongoing evaluation of the patient*s mental status during the study - CNS trauma or active seizure disorders requiring medication - Significant cardiovascular dysfunction within the past 6 months (e.g. angina, congestive heart failure, recent myocardial infarction, severe hypertension or significant arrhythmia). - Poorly controlled diabetes mellitus - Significant pulmonary dysfunction/chronic disease (e.g. chronic obstructive pulmonary disease) - Renal insufficiency (elevated serum creatinine) - Pregnancy, lactation - Substance abuse, such as alcohol (80 gram/day), I.V. drugs and inhaled drugs. If the subject has a history of substance abuse, to be considered for inclusion into the protocol, the subject must have abstained from using the abused substance for at least 2 years. Subjects receiving methadone within the past 2 years are also excluded - Positive stool culture for enteric pathogens - Any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in and completing the study.
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| -Proportion of patients in clinical and endoscopic remission. Clinical remission is defined as a Mayo score 1, and endoscopic remission is defined as no visible inflammation (i.e. mayo sub-score 0-1). - Proportion of patients with endoscopic response, defined as a decrease in Mayo sub-score of >= 1 and/or a decrease in extent of inflammation of >= 5 cm from baseline. -Safety and tolerability of tacrolimus suppositories and beclomethasone suppositories. -Quality of life (IBDQ). -Changes in histopathology from biopsies taken before and after treatment (grading scale (0 _ structural changes only, 1_ chronic inflammation, 2 _ lamina propria neutrophils, 3_ neutrophils in epithelium, 4 _ crypt destruction, 5 _ erosions or ulcers)). | — |
Primary
| Measure | Time frame |
|---|---|
| -The primary end point will be the proportion of patients with clinical response at day 28 after treatment with tacrolimus suppositories compared to beclomethasone suppositories. Clinical response is defined as an absolute decrease in Mayo score of >=3 from baseline and a relative decrease from baseline of >=30% with accompanying decrease in the rectal bleeding subscore of >=1 point or absolute rectal bleeding subscore of 0 or 1. | — |
Countries
Netherlands
Outcome results
None listed