Efficacy of Infliximab in the Treatment of Patients Affected by Corticodependent Crohn's Disease (P02732)
Primary Purpose
Crohn's Disease
Status
Terminated
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Infliximab
AZA
Placebo Prednisolone
Prednisolone
AZA
Placebo Infliximab
Sponsored by
About this trial
This is an interventional treatment trial for Crohn's Disease
Eligibility Criteria
Inclusion Criteria:
- Male and Female patients with age between 18 and 65 years.
- Patients suffering from corticodependent Crohn's disease, in reheightening phase, with CDAI value >=220.
- Patients able to participate and to comply with the study.
- Patients with adequate bone marrow stock: GB >=3.5x109/L, PLTs >=100 x 103, Hb >=9 gr/dL.
- Patients able and willing to give written informed consent.
Exclusion Criteria:
- Patients with abscesses or active perianal diseases.
- Clinically symptomatic and/or with retrodilatation intestinal stenosis.
- Patients previously treated with infliximab.
- Patients with history of allergy to murine proteins.
- Treatment with immunosuppressant such as AZA, 6-mercaptopurine, methotrexate and cyclosporine A during the previous 3 months.
- Positive feces exams for intestinal pathogens, parasitic or toxin of clostridium difficilis.
- Tuberculosis (TBC) both active and inactive, evaluated by means of a detailed description (personal history of tuberculosis or possible previous contact with a source of TBC infection), and appropriate screening tests, Thorax Rx, tuberculin test.
- Presence of severe infections such as hepatitis, pneumonia, pyelonephritis within the past 3 months before the enrolment. Less severe infections, such as those in charge of the upper respiratory tract (cold syndrome), are not considered exclusion criteria as well as the uncomplicated urinary tract infections, contracted during the previous 3 months before study inclusion.
- Ongoing infections due to CMV, pneumocystis carinii, atypical mycobacterium. Proved HIV infection, presence of ARC or AIDS.
- Necessity during the study of elective or emergency surgical operation.
- Altered hepatic function: total bilirubin >=1.5 times the upper limit of the normal ranges (UNL), AST (SGOT) >=2 UNL, phosphatase alkaline >=2.5 UNL, or PTT - INR >=1.5 UNL.
- Altered renal function: creatinine >=1.5 mg.
- Presence of serious concomitant illnesses (cardiac, pulmonary, neurological diseases).
- History of pathology in charge of the haemopoietic system and of lymphoproliferative diseases such as lymphoma, lymphadenopathies of unusual localisation (i.e. at the nape, epitochlear or periaortic) or splenomegaly.
- Presence of neoplastic or pre-neoplastic lesions, or history of neoplasm in the past 5 years.
- Presence or history of drug or alcohol abuse.
- Pregnant or lactating women.
- Women of childbearing potential without adequate contraception except in case of surgical menopause. These methods of birth control should also be used during the 6 months after the last infusion.
- Contraindications for AZA (i.e. lymphoproliferative diseases, leukopenia) and prednisolone (i.e. peptic ulcer, systemic fungal infections) as laid out in the summary of product characteristics.
- Hyperamylasemia >=1.5 times the upper limit of the normal ranges.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Group A
Group B
Arm Description
Outcomes
Primary Outcome Measures
To evaluate the therapeutic efficacy of repeated infliximab infusions in order to maintain Crohn's disease remission (Crohn's disease Activity Index [CDAI] <=150) at the end of the study.
Secondary Outcome Measures
Tolerability evaluation (labs parameters, vital signs, adverse events).
Quality of life assessment, by IBDQ questionnaire.
Full Information
NCT ID
NCT00796250
First Posted
November 21, 2008
Last Updated
March 21, 2017
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT00796250
Brief Title
Efficacy of Infliximab in the Treatment of Patients Affected by Corticodependent Crohn's Disease (P02732)
Official Title
Efficacy of Infliximab as "Bridging Therapy" in the Treatment of Patients Affected by Corticodependent Crohn's Disease Under Standard Treatment With Azathioprine
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Terminated
Why Stopped
Due to poor patient recruitment, a decision was made to terminate this trial.
Study Start Date
November 1, 2003 (Actual)
Primary Completion Date
January 1, 2005 (Actual)
Study Completion Date
January 1, 2005 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a double-blind, double-dummy, prednisolone-controlled, multi-center, randomized, parallel-group clinical study to evaluate the therapeutic efficacy of repeated infliximab infusions in order to maintain Crohn's disease remission at the end of the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn's Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group A
Arm Type
Experimental
Arm Title
Group B
Arm Type
Active Comparator
Intervention Type
Biological
Intervention Name(s)
Infliximab
Other Intervention Name(s)
Remicade, SCH 215596
Intervention Description
Patients in this group were treated with azathioprine (AZA), infliximab, and placebo prednisolone. Infliximab was to be administered at a dose of 5 mg/kg at Visit 2 (Week 0), and at Weeks 2, 6, and 14 (total of four infusions). Infliximab infusions were administered by the investigators in the hospital during the patient's visit, usually in the morning.
Intervention Type
Drug
Intervention Name(s)
AZA
Other Intervention Name(s)
Imuran
Intervention Description
Patients in this group were treated with AZA, infliximab, and placebo prednisolone. All patients were treated with AZA, by oral use, with a 2 mgkg dose a day until the end of the study (30 weeks).
Intervention Type
Drug
Intervention Name(s)
Placebo Prednisolone
Other Intervention Name(s)
Placebo
Intervention Description
Patients in this group were treated with AZA, infliximab, and placebo prednisolone. Placebo prednisolone was to be administered by oral use.
Intervention Type
Drug
Intervention Name(s)
Prednisolone
Other Intervention Name(s)
Pediapred
Intervention Description
Patients in this group were treated with AZA, prednisolone, and placebo infliximab. Prednisolone was to be administered by oral use, with the decreasing dose of 40 mg a day, 35 mg a day, 30 mg a day and 25 mg a day every week for each dosage, respectively; 20 mg a day for five weeks; 15 mg a day, 10 mg a day and 5 mg a day for one week for each dosage respectively, until discontinuation.
Intervention Type
Drug
Intervention Name(s)
AZA
Other Intervention Name(s)
Imuran
Intervention Description
Patients in this group were treated with AZA, prednisolone, and placebo infliximab. All patients were treated with AZA, by oral use, with a 2 mgkg dose a day until the end of the study (30 weeks).
Intervention Type
Biological
Intervention Name(s)
Placebo Infliximab
Other Intervention Name(s)
Placebo
Intervention Description
Patients in this group were treated with AZA, prednisolone, and placebo infliximab. Placebo infliximab was to be administered at Visit 2 (Week 0), and at Weeks 2, 6, and 14 (total of four infusions). Infliximab infusions were administered by the investigators in the hospital during the patient's visit, usually in the morning.
Primary Outcome Measure Information:
Title
To evaluate the therapeutic efficacy of repeated infliximab infusions in order to maintain Crohn's disease remission (Crohn's disease Activity Index [CDAI] <=150) at the end of the study.
Time Frame
Week 30
Secondary Outcome Measure Information:
Title
Tolerability evaluation (labs parameters, vital signs, adverse events).
Time Frame
At each visit.
Title
Quality of life assessment, by IBDQ questionnaire.
Time Frame
Baseline, Week 10, and Week 30.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male and Female patients with age between 18 and 65 years.
Patients suffering from corticodependent Crohn's disease, in reheightening phase, with CDAI value >=220.
Patients able to participate and to comply with the study.
Patients with adequate bone marrow stock: GB >=3.5x109/L, PLTs >=100 x 103, Hb >=9 gr/dL.
Patients able and willing to give written informed consent.
Exclusion Criteria:
Patients with abscesses or active perianal diseases.
Clinically symptomatic and/or with retrodilatation intestinal stenosis.
Patients previously treated with infliximab.
Patients with history of allergy to murine proteins.
Treatment with immunosuppressant such as AZA, 6-mercaptopurine, methotrexate and cyclosporine A during the previous 3 months.
Positive feces exams for intestinal pathogens, parasitic or toxin of clostridium difficilis.
Tuberculosis (TBC) both active and inactive, evaluated by means of a detailed description (personal history of tuberculosis or possible previous contact with a source of TBC infection), and appropriate screening tests, Thorax Rx, tuberculin test.
Presence of severe infections such as hepatitis, pneumonia, pyelonephritis within the past 3 months before the enrolment. Less severe infections, such as those in charge of the upper respiratory tract (cold syndrome), are not considered exclusion criteria as well as the uncomplicated urinary tract infections, contracted during the previous 3 months before study inclusion.
Ongoing infections due to CMV, pneumocystis carinii, atypical mycobacterium. Proved HIV infection, presence of ARC or AIDS.
Necessity during the study of elective or emergency surgical operation.
Altered hepatic function: total bilirubin >=1.5 times the upper limit of the normal ranges (UNL), AST (SGOT) >=2 UNL, phosphatase alkaline >=2.5 UNL, or PTT - INR >=1.5 UNL.
Altered renal function: creatinine >=1.5 mg.
Presence of serious concomitant illnesses (cardiac, pulmonary, neurological diseases).
History of pathology in charge of the haemopoietic system and of lymphoproliferative diseases such as lymphoma, lymphadenopathies of unusual localisation (i.e. at the nape, epitochlear or periaortic) or splenomegaly.
Presence of neoplastic or pre-neoplastic lesions, or history of neoplasm in the past 5 years.
Presence or history of drug or alcohol abuse.
Pregnant or lactating women.
Women of childbearing potential without adequate contraception except in case of surgical menopause. These methods of birth control should also be used during the 6 months after the last infusion.
Contraindications for AZA (i.e. lymphoproliferative diseases, leukopenia) and prednisolone (i.e. peptic ulcer, systemic fungal infections) as laid out in the summary of product characteristics.
Hyperamylasemia >=1.5 times the upper limit of the normal ranges.
12. IPD Sharing Statement
Citations:
PubMed Identifier
21688345
Citation
Leombruno JP, Nguyen GC, Grootendorst P, Juurlink D, Einarson T. Hospitalization and surgical rates in patients with Crohn's disease treated with infliximab: a matched analysis. Pharmacoepidemiol Drug Saf. 2011 Aug;20(8):838-48. doi: 10.1002/pds.2132. Epub 2011 Jun 17.
Results Reference
result
Available IPD and Supporting Information:
Available IPD/Information Type
CSR Synopsis
Available IPD/Information URL
http://www.merck.com/clinical-trials/policies-perspectives.html
Learn more about this trial
Efficacy of Infliximab in the Treatment of Patients Affected by Corticodependent Crohn's Disease (P02732)
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