Comparison of 2 Immunomodulator Withdrawal Schemes for Infliximab Monotherapy in Active Pediatric Crohn's Disease After Thiopurine Failure (WITHDRAW)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2014 by Wolfson Medical Center
Sponsor:
Information provided by (Responsible Party):
Prof. Arie Levine, Wolfson Medical Center
ClinicalTrials.gov Identifier:
NCT01802593
First received: December 24, 2012
Last updated: December 11, 2014
Last verified: December 2014
  Purpose

The goal of the present study is to evaluate the best regimen for infliximab monotherapy, and to evaluate if limited combination therapy with IFX and an Immunomodulator for the first 6 months of therapy, in prior Immunomodulator failures, is superior to monotherapy with Immunomodulator cessation from the second infusion, in preventing loss of remission to IFX.


Condition Intervention Phase
Crohn's Disease
Drug: AZATHIOPRINE or METHOTREXATE
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 4, Open Label Multicenter Randomized Controlled Trial. Comparison of 2 Immunomodulator Withdrawal Schemes for Infliximab Monotherapy in Active Pediatric Crohn's Disease After Immunomodulator Failure

Resource links provided by NLM:


Further study details as provided by Wolfson Medical Center:

Primary Outcome Measures:
  • Complete or partial LAR (lack of remission) [ Time Frame: 76 weeks ] [ Designated as safety issue: No ]
    • Complete LAR- Patient failing to achieve remission after first 3 scheduled doses , or absence of remission 7 days after an infliximab infusion in a patient who had achieved remission after any previous infusion, and unresponsive to dose escalation or dose interval change, or relapse occurring less than 4 weeks after last infusion
    • Partial LAR- Relapse 4-8 weeks after previous infusion, with requirement for dose escalation or shortening of infliximab schedule, and remission with change in dosing or interval.


Secondary Outcome Measures:
  • Mean trough level [ Time Frame: 14 and 52 weeks ] [ Designated as safety issue: No ]
  • Sustained steroid free remission [ Time Frame: 52 and 76 weeks ] [ Designated as safety issue: No ]
  • Presence of ATI [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Corticosteroid free remission [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
  • Hospitalizations for LOR (loss of response) or failure to obtain remission [ Time Frame: Up to 76 weeks ] [ Designated as safety issue: No ]
  • Medication associated adverse events [ Time Frame: Up to 76 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 90
Study Start Date: February 2013
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Immunomodulator therapy 26 weeks
IFX 5mg/kg for 76 weeks, continuing immunomodulator for 6 months from first infusion
Drug: AZATHIOPRINE or METHOTREXATE
Patients should continue azathioprine or 6 MP or methotrexate at their previous doses for 6 months IMM therapy 26 weeks
Other Name: 6 MERCAPTOPURINE
Experimental: Immunomodulator therapy 2 weeks
IFX 5mg/kg induction for 76 weeks, discontinuing immunomodulator on day of second infusion( after 14 days).
Drug: AZATHIOPRINE or METHOTREXATE

Patients should continue the same dose of azathioprine or 6 MP or methotrexate until the day of the second infusion (week 2)

Thiopurine therapy 2 weeks

Other Name: 6 MERCAPTOPURINE

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   6 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Crohns disease
  2. Age: 6 - 18 years ( inclusive)
  3. Active disease PCDAI >10, or any steroid dependence despite thiopurine use for >10 weeks.
  4. Naïve to biologics
  5. Informed consent
  6. CRP ≥0.6 mg/dl
  7. Neg. TB-Test, negative HBV- S Ag
  8. Use of IMM at present or in past for at least 10 weeks ( for Withdraw only).
  9. Negative stool culture, parasites and clostridium toxin current flare

Inclusion criteria Comments:

  1. Patients receiving corticosteroids may be included if the disease is active and CRP elevated.
  2. All other treatments such as 5ASA , , must be discontinued immediately after the first IFX infusion.
  3. Patients may receive an antihistamine prior to any infusion.Use of corticosteroid pretreatment is allowed only during the first two infusions (single infusion on day of infliximab), or if an infusion reaction has occurred.
  4. Partial enteral nutrition, accounting for less than 50% of daily required calories, may be supplied as needed.
  5. Patients receiving antibiotics must cease use of antibiotics within the 14 days of receiving the first infusion.
  6. ESR >20 can be alternative if the CRP <0.6.
  7. Negative stool culture, parasites and clostridium toxin current flare will examined only if the patient has diarrhea.
  8. Patients may be enrolled directly in to the Predict study , in which case duration of IMM is irrelevant , but patients must have received an IMM until week 2 as in the withdraw

Exclusion Criteria:

  1. Intolerance to thiopurines/methotrexate
  2. Pregnancy
  3. Contraindication for any of the drugs.
  4. Leukopenia <4000 or absolute neutrophil count below 1200 on two consecutive tests during screening.
  5. Hepatocellular Liver disease ( ALT > 60 ) or cirrhosis.
  6. Renal Failure
  7. Prior idiosyncratic side effects with thiopurines ( pancreatitis etc).
  8. Current abscess ( < 14 days of antibiotics) or perforation of the bowel( <14 days antibiotics).
  9. Small bowel obstruction within the last 3 months
  10. Fixed non inflammatory stricture with predilatation with symptoms related to stricture
  11. Complicated or heavily draining perianal fistula ( indolent non draining or scant draining fistula are not exclusion criteria)
  12. Prior treatment with infliximab
  13. Previous malignancy
  14. Toxic Megacolon
  15. Sepsis
  16. Surgery related to Crohn's disease in previous 8 weeks.
  17. Positive Hepatitis B surface antigen or evidence for TB.
  18. Current bacterial infection
  19. IBD unclassified

Exclusion criteria Comments:

1. Prior surgery or post operative recurrence are not exclusion criteria.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01802593

Contacts
Contact: Arie Levine Levine, MD 972-3-5028808 alevine@wolfson.health.gov.il

Locations
Israel
The E. Wolfson.Medical Center Recruiting
Holon, Israel, 58100
Contact: Arie Levine, MD    972-3-5028808    alevine@wolfson.health.gov.il   
Principal Investigator: Arie Levine, MD         
Sponsors and Collaborators
Prof. Arie Levine
Investigators
Study Chair: Arie Levine, MD Pediatric Gastroenterology and Nutrition Unit, The E. Wolfson MC, Tel-Aviv University, Holon, Israel
Study Director: Dan Turner, MD, PhD Pediatric Gastroenterology and Nutrition Unit, The Hebrew University of Jerusalem, Shaare Zedek MC, Jerusalem, Israel
Principal Investigator: Raanan Shamir, MD Schneider Childrens Hospital
Principal Investigator: Michal Kori, MD Kaplan Medical Center
Principal Investigator: Michael Wilshanski, MD Hadassah Medical Center
Principal Investigator: Ron Shaoul, MD Meyer Childrens Hospital Rambam, Haifa, Israel
Principal Investigator: Shlomi Cohen, MD Tel Aviv Medical Center
Principal Investigator: Batia Weiss, MD Sheba Medical Center
Principal Investigator: Sarit Peleg, MD Afula Hospital
Principal Investigator: Baruch Yerushalmi, MD Soroka Medical Center
Principal Investigator: Efrat Broide, MD Asaf Harofe Medical Center
Principal Investigator: Avi On, MD Poriah Hospital
Principal Investigator: Hussein Chemali, MD Nazheret Hospital
Principal Investigator: Aharon Lerner, MD Carmel Hospital
  More Information

No publications provided

Responsible Party: Prof. Arie Levine, Director, Pediatric Gastroenterology and Nutrition unit., Wolfson Medical Center
ClinicalTrials.gov Identifier: NCT01802593     History of Changes
Other Study ID Numbers: 0169-12-WOMC
Study First Received: December 24, 2012
Last Updated: December 11, 2014
Health Authority: Israel: Ministry of Health

Keywords provided by Wolfson Medical Center:
Pediatric
Crohn's disease
Infliximab
Thiopurine

Additional relevant MeSH terms:
Crohn Disease
Digestive System Diseases
Gastroenteritis
Gastrointestinal Diseases
Inflammatory Bowel Diseases
Intestinal Diseases
6-Mercaptopurine
Adjuvants, Immunologic
Azathioprine
Immunologic Factors
Infliximab
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Central Nervous System Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Gastrointestinal Agents
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on August 31, 2015