Working… Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01802593
Recruitment Status : Terminated (lack of budget and failure to reach milestones)
First Posted : March 1, 2013
Last Update Posted : December 22, 2015
Information provided by (Responsible Party):
Prof. Arie Levine, Wolfson Medical Center

Brief Summary:
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 or disease Intervention/treatment Phase
Crohn's Disease Drug: AZATHIOPRINE or METHOTREXATE Phase 4

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : February 2013
Actual Primary Completion Date : December 2015
Actual Study Completion Date : December 2015

Arm Intervention/treatment
Experimental: Immunomodulator therapy 26 weeks
IFX 5mg/kg for 76 weeks, continuing immunomodulator for 6 months from first infusion
Patients should continue azathioprine or 6 MP or methotrexate at their previous doses for 6 months IMM therapy 26 weeks

Experimental: Immunomodulator therapy 2 weeks
IFX 5mg/kg induction for 76 weeks, discontinuing immunomodulator on day of second infusion( after 14 days).

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


Primary Outcome Measures :
  1. Complete or partial LAR (lack of remission) [ Time Frame: 76 weeks ]
    • 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 :
  1. Mean trough level [ Time Frame: 14 and 52 weeks ]
  2. Sustained steroid free remission [ Time Frame: 52 and 76 weeks ]
  3. Presence of ATI [ Time Frame: 52 weeks ]
  4. Corticosteroid free remission [ Time Frame: 14 weeks ]
  5. Hospitalizations for LOR (loss of response) or failure to obtain remission [ Time Frame: Up to 76 weeks ]
  6. Medication associated adverse events [ Time Frame: Up to 76 weeks ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   6 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01802593

Layout table for location information
The E. Wolfson.Medical Center
Holon, Israel, 58100
Sponsors and Collaborators
Prof. Arie Levine
Layout table for investigator information
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 University 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
Layout table for additonal information
Responsible Party: Prof. Arie Levine, Director, Pediatric Gastroenterology and Nutrition unit., Wolfson Medical Center Identifier: NCT01802593    
Other Study ID Numbers: 0169-12-WOMC
First Posted: March 1, 2013    Key Record Dates
Last Update Posted: December 22, 2015
Last Verified: December 2015
Keywords provided by Prof. Arie Levine, Wolfson Medical Center:
Crohn's disease
Additional relevant MeSH terms:
Layout table for MeSH terms
Crohn Disease
Inflammatory Bowel Diseases
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors