Mercaptopurine Therapy in Ulcerative Colitis

Colitis, Ulcerative Clinical Trial

— OPTIC  

Official title:

Efficacy of Optimized Thiopurine Therapy in Ulcerative Colitis (OPTIC)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02910245
• Other study ID #: SA652012
• Status: Recruiting
• Phase: Phase 3
• Start date: November 2016
• Est. completion date: April 30, 2022

Study information

• Verified date: January 2020
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: Mark Löwenberg, MD, PhD
• Phone: +31205667621
• Email: m.lowenberg[@]amc.uva.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 136
• Est. completion date: April 30, 2022
• Est. primary completion date: April 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer

Intervention

Drug:
• Mercaptopurine (Purinethol)

• Placebo

• Mesalamine

• Prednisone

Locations

Country	Name	City	State
Netherlands	Noordwest Ziekenhuisgroep	Alkmaar
Netherlands	Flevoziekenhuis	Almere
Netherlands	Meander MC	Amersfoort
Netherlands	Amstelland Hospital	Amsterdam
Netherlands	Amsterdam UMC, location AMC	Amsterdam
Netherlands	Amsterdam UMC, location VUMC	Amsterdam
Netherlands	OLVG Oost	Amsterdam
Netherlands	MC Haaglanden	Den Haag
Netherlands	Tergooi Hospital	Hilversum
Netherlands	Westfriesgasthuis	Hoorn
Netherlands	St. Antonius Hospital	Nieuwegein
Netherlands	Sint Franciscus Gasthuis	Rotterdam

Sponsors (2)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)	ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Disease specific quality of life	Quality of life measured by use of the IBD questionnaire (IBDQ)	Every 3 months during 52 weeks of treatment
Primary	Clinical and endoscopic remission	Defined as a SCCAI-score = 4, a UCEIS-score = 3 and a total Mayo score = 2, with no individual subscore >1.	After 52 weeks of treatment
Secondary	(Serious) Adverse Events	Occurrence of (serious) adverse events ((S)AE)	Continue during 52 weeks of treatment
Secondary	Leukocyte counts		Every 6 weeks during 52 weeks of treatment
Secondary	Liver function tests		Every 6-12 weeks during 52 weeks of treatment
Secondary	Occurrence of subjective thiopurine intolerance		Every 6-12 weeks during 52 weeks of treatment
Secondary	6-TGN levels		Every 6-12 weeks during 52 weeks of treatment
Secondary	6-MMP levels		Every 6-12 weeks during 52 weeks of treatment
Secondary	Occurrence of treatment failure		Continue during 52 weeks of treatment
Secondary	Occurrence of upscaling treatment	Occurrence of upscaling treatment to biologicals (anti-TNF agents or vedolizumab)	Continue during 52 weeks of treatment
Secondary	Treatment costs	Budget-impact analysis and cost-utility analysis	Every 3 months during 52 weeks of treatment