Clincosm LogoSign in Get a demo

OPTIC: Mercaptopurine Therapy in Ulcerative Colitis

Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) (Other)
Overall Status
Unknown status
CT.gov ID
NCT02910245
Collaborator
ZonMw: The Netherlands Organisation for Health Research and Development (Other)
136
Enrollment
12
Locations
2
Arms
65.9
Anticipated Duration (Months)
11.3
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
136 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Efficacy of Optimized Thiopurine Therapy in Ulcerative Colitis (OPTIC)
Actual Study Start Date :
Nov 1, 2016
Anticipated Primary Completion Date :
Apr 30, 2022
Anticipated Study Completion Date :
Apr 30, 2022

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Mercaptopurine (Purinethol)

Mercaptopurine (Purinethol),1-1.5 mg/kg/day oral, 52 weeks & Prednisone, 40 mg/day oral, 2 weeks, followed by fixed tapering over 6 weeks OR budesonide (cortiment) 9 mg/day during 8 weeks & Mesalamine, 2 g/day oral, 52 weeks.

Drug: Mercaptopurine (Purinethol)
Other Names:
  • Purinethol

    • Drug: Mesalamine
    Other Names:
  • Asacol
  • Mezavant
  • Pentasa
  • Salofalk

    • Drug: Prednisone
    Placebo Comparator: Placebo

    Placebo, 1-1.5 mg/kg/day, 52 weeks & Prednisone, 40 mg/day oral, 2 weeks, followed by fixed tapering over 6 weeks OR budesonide (cortiment) 9 mg/day during 8 weeks & Mesalamine, 2 g/day oral, 52 weeks.

    Drug: Placebo

    Drug: Mesalamine
    Other Names:
  • Asacol
  • Mezavant
  • Pentasa
  • Salofalk

    • Drug: Prednisone

    Outcome Measures

    Primary Outcome Measures

    1. Clinical and endoscopic remission [After 52 weeks of treatment]

      Defined as a SCCAI-score ≤ 4, a UCEIS-score ≤ 3 and a total Mayo score ≤ 2, with no individual subscore >1.

    Secondary Outcome Measures

    1. (Serious) Adverse Events [Continue during 52 weeks of treatment]

      Occurrence of (serious) adverse events ((S)AE)

    2. Leukocyte counts [Every 6 weeks during 52 weeks of treatment]

    3. Liver function tests [Every 6-12 weeks during 52 weeks of treatment]

    4. Occurrence of subjective thiopurine intolerance [Every 6-12 weeks during 52 weeks of treatment]

    5. 6-TGN levels [Every 6-12 weeks during 52 weeks of treatment]

    6. 6-MMP levels [Every 6-12 weeks during 52 weeks of treatment]

    7. Occurrence of treatment failure [Continue during 52 weeks of treatment]

    8. Occurrence of upscaling treatment [Continue during 52 weeks of treatment]

      Occurrence of upscaling treatment to biologicals (anti-TNF agents or vedolizumab)

    9. Treatment costs [Every 3 months during 52 weeks of treatment]

      Budget-impact analysis and cost-utility analysis

    Other Outcome Measures

    1. Disease specific quality of life [Every 3 months during 52 weeks of treatment]

      Quality of life measured by use of the IBD questionnaire (IBDQ)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Noordwest Ziekenhuisgroep Alkmaar Netherlands
    2 Flevoziekenhuis Almere Netherlands
    3 Meander MC Amersfoort Netherlands 3813 TZ
    4 Amsterdam UMC, location VUMC Amsterdam Netherlands 1081 HZ
    5 OLVG Oost Amsterdam Netherlands 1090 HM
    6 Amsterdam UMC, location AMC Amsterdam Netherlands 1105AZ
    7 Amstelland Hospital Amsterdam Netherlands
    8 MC Haaglanden Den Haag Netherlands 2512 VA
    9 Tergooi Hospital Hilversum Netherlands 1213 XZ
    10 Westfriesgasthuis Hoorn Netherlands
    11 St. Antonius Hospital Nieuwegein Netherlands 3435 CM
    12 Sint Franciscus Gasthuis Rotterdam Netherlands

    Sponsors and Collaborators

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

    Investigators

    • Principal Investigator: Mark Löwenberg, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    M. Lowenberg, Gastroenterologist, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
    ClinicalTrials.gov Identifier:
    NCT02910245
    Other Study ID Numbers:
    • SA652012
    First Posted:
    Sep 22, 2016
    Last Update Posted:
    Jan 7, 2020
    Last Verified:
    Jan 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by M. Lowenberg, Gastroenterologist, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
    Therapeutic Drug Monitoring
    Mercaptopurine (6-MP)
    Thiopurine
    Efficacy
    Additional relevant MeSH terms:
    Colitis
    Colitis, Ulcerative
    Ulcer
    Prednisone
    Mesalamine
    Mercaptopurine

    Study Results

    No Results Posted as of Jan 7, 2020