Clinical trial NCT02910245: Mercaptopurine Therapy in Ulcerative Colitis
Official title: Efficacy of Optimized Thiopurine Therapy in Ulcerative Colitis (OPTIC)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Colitis, Ulcerative
Keywords: Therapeutic Drug Monitoring
Mercaptopurine (6-MP)
Thiopurine
Efficacy
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2016-09-22
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This project is a double-blind, randomized, placebo-controlled, multicenter trial in the Netherlands. The aim of this study is to investigate the therapeutic efficacy of optimized 6-mercaptopurine (6-MP) in ulcerative colitis patients. Therapeutic drug monitoring (TDM) will be performed in order to optimize treatment outcomes and objective endoscopic endpoints will be used.

Detailed description: Subjects will receive treatment with oral prednisone 40 mg/day for 2 weeks, followed by fixed tapering over 6 weeks. Half of the subjects will be randomized to concomitant 6-MP 1-1.5 mg/kg/day and half will receive concomitant placebo treatment. During the entire course of the trial all subjects will receive maintenance treatment with 5-ASA in an oral dose of at least 2 gram per day. Subjects will be subjected to one colonoscopy at baseline and one sigmoidoscopy in week 52 in order to assess endoscopic disease activity.

Data will be collected using electronic case report forms (eCRF) with Castor EDC. Quality and data validation procedures will be applied to ensure the validity and accuracy of the clinical database. Monitoring of the study will be done according to the GCP guidelines and following a monitoring plan. The financier of the study, ZonMw Goed Gebruik Geneesmiddelen, has the right to perform an audit if seen necessary.

Eligibility criteria: Inclusion Criteria:

1. Confirmed diagnosis of UC by endoscopy and histopathology
2. Patients between 18 and 80 years of age
3. Active disease, despite oral treatment with at least 2g/day 5-ASA
4. Treatment with oral corticosteroids is required

Exclusion Criteria:

1. Prior treatment with thiopurines
2. Prior treatment with biologics (e.g. anti-TNF agents and vedolizumab)
3. Current pregnancy (a pregnancy test will be performed if necessary according to the treating physician)
4. Chronic Obstructive Pulmonary Disease (COPD)
5. Acute coronary heart disease
6. (Bacterial) gastroenteritis has to be treated first
7. Coagulation disorders
8. Active malignancy
9. History of colonic dysplasia/cancer
10. Extensive colonic resection, i.e. subtotal colectomy with \<15 cm colon in situ
11. Concomitant therapy with drugs interfering with MP metabolism, like allopurinol, ribavirin or anti-epileptics.
12. Known systemic fungal infections or parasitic infections have to be treated first
13. Known duodenal or ventricular ulcus
14. Substance abuse, such as alcohol (\> 80 gram/day - one standard glass contains 10 gram of alcohol), 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
15. Positive tuberculosis screen (when a screening is performed at the discretion of the treating physician)
16. Active hepatitis B virus or hepatitis C virus infection defined as a positive anti-HCV, HBsAg and/or anti-HBcore screening.
17. Leucopenia (Neutrophil count \< 1,8x10\^9/L)
18. Thrombopenia (Platelets \< 90x10\^9/L)
19. Elevated liver enzymes (\>2x ULN)
20. Abnormal renal function (eGFR\< 30 mL/min)
21. Other conditions which in the opinion of the investigator may interfere with the subject's ability to comply with the study procedure

Primary outcomes:
measure: Clinical and endoscopic remission
timeFrame: After 52 weeks of treatment
Secondary outcomes:
measure: (Serious) Adverse Events
timeFrame: Continue during 52 weeks of treatment
measure: Leukocyte counts
timeFrame: Every 6 weeks during 52 weeks of treatment
measure: Liver function tests
timeFrame: Every 6-12 weeks during 52 weeks of treatment
measure: Occurrence of subjective thiopurine intolerance
timeFrame: Every 6-12 weeks during 52 weeks of treatment
measure: 6-TGN levels
timeFrame: Every 6-12 weeks during 52 weeks of treatment
measure: 6-MMP levels
timeFrame: Every 6-12 weeks during 52 weeks of treatment
measure: Occurrence of treatment failure
timeFrame: Continue during 52 weeks of treatment
measure: Occurrence of upscaling treatment
timeFrame: Continue during 52 weeks of treatment
measure: Treatment costs
timeFrame: Every 3 months during 52 weeks of treatment
Other outcomes:
measure: Disease specific quality of life
timeFrame: Every 3 months during 52 weeks of treatment
Locations:
city: Alkmaar
country: Netherlands
facility: Noordwest Ziekenhuisgroep
city: Almere
country: Netherlands
facility: Flevoziekenhuis
city: Amersfoort
country: Netherlands
facility: Meander MC
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, location VUMC
city: Amsterdam
country: Netherlands
facility: OLVG Oost
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, location AMC
city: Amsterdam
country: Netherlands
facility: Amstelland Hospital
city: Den Haag
country: Netherlands
facility: MC Haaglanden
city: Hilversum
country: Netherlands
facility: Tergooi Hospital
city: Hoorn
country: Netherlands
facility: Westfriesgasthuis
city: Nieuwegein
country: Netherlands
facility: St. Antonius Hospital
city: Rotterdam
country: Netherlands
facility: Sint Franciscus Gasthuis
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Mark Löwenberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: