Efficacy Study of Granulocytapheresis Plus Steroids vs Steroids Alone in Active Steroid Dependant Ulcerative Colitis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of the addition of GMA apheresis to steroid conventional treatment for achieving and maintaining remission in Active steroid dependant Ulcerative Colitis patients

Detailed Description
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This is a multicenter randomized controlled trial which will compare the efficacy and safety of Adacolumn GMA apheresis plus oral steroids vs steroids alone in a strictly selected population of moderate to severe active steroid dependant Ulcerative Colitis patients.

Official Title
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An Open Randomized Multicenter Clinical Investigation to Compare the Efficacy and Safety of Prednisone Plus Adacolumn® GMA Apheresis vs Prednisone Alone in the Treatment of Patients With Mild or Moderately Active Steroid Dependent Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Device: Granulocyte Monocyte Apheresis (GMA-Apheresis)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 - 75 years old Active ulcerative colitis with documented clinical symptoms and endoscopic findings Active disease defined as DAI (Mayo score) ≥ 4 and ≤10 with at least 1 point in flexible sigmoidoscopy Steroid dependency as defined by: A. Inability to withdraw corticosteroids within three months of starting treatment, without recurrent active disease B. appearance of relapse within 3 months after withdrawal of corticosteroids Colonic involvement with ulcerative colitis beyond 15cm of the anal verge Stable doses:A. Aminosalicylates for the last 4 weeks B. Prednisolone or equivalent dose ≤ 20 mg/day for the last 2 weeks C. Azathioprine or 6-mercaptopurine at stable dose for the last 12 weeks Signed informed consent form Agree to participate in the required follow-up visits Able to complete the diary Exclusion Criteria: Febrile (> 38ºC) Evidence of toxic megacolon Anticipated need for surgery within 24 weeks Known obstructive diseases of the gastrointestinal system Proctocolectomy, total colectomy, ileostomy, stoma or ileal pouch-anal anastomosis A history of allergic reaction to heparin or heparin-induced thrombocytopenia A history of hypersensitivity reaction associated with an apheresis procedure or intolerance of apheresis procedures Requires a central venous access catheter for the apheresis treatments Known infection with enteric pathogens, pathogenic ova or parasites, C. difficile toxin or CMV Hypotension (systolic blood pressure <80 mmHg and/or diastolic blood pressure <50 mmHg) at screening visit only Uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >120 mmHg) despite medical therapy A history of myocardial infarction or unstable angina within the past 6 months A history of coronary artery bypass grafting surgery or angioplasty within the past 6 months Prosthetic heart valve, pacemaker or other permanent implant Severe cardiovascular or peripheral vascular disease, severe renal disease Liver disease defined as levels of SGOT [AST], SGPT [ALT] or alkaline phosphatase >2.5x the upper limit of the normal range for the laboratory performing test History of cirrhosis Known bleeding disorder (PT or PTT>1.5x the upper limit of the normal range for the laboratory performing the test), or concomitant anticoagulant therapy for purposes other than apheresis treatment Prior history suggestive of a hypercoagulable disorder, including 1 or more episodes of pulmonary embolism or deep vein thrombosis Known infection with Hepatitis B or C, or HIV Abnormal hematology parameters defined as severe anemia with hemoglobin <8.5g/dL, white blood cell count of <3,500/μl and a granulocyte count < 2,000/μl Fibrinogen level >700mg/dL Major surgery within the past 6 months Infection:Active infections less than 4 weeks from successful completion of antibiotic treatment for routine bacterial infectionFebrile viral infection within 4 weeks of entry into the clinical investigationLess than 12 weeks from conclusion of therapy for systemic fungal infections Malignancy within the past 2 years other than surgically cured skin carcinoma or cervical dysplasia (CIN I-II) History of dysplasia or carcinoma of the colon or lack of a complete colonoscopy in the last 12 months in patients with longstanding UC (> 10 años) Current drug or alcohol abuse Pregnant, lactating or planning to become pregnant during the course of the clinical investigation Used within the last 30 days an investigational drug, biologic or device or 5 half-lifes, if known, for any investigational drug or biologic Received cyclosporine or tacrolimus within the last 8 weeks Received infliximab within the last 8 weeks Fulminant ulcerative colitis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Seven apheresis treatments over seven consecutive weeks (1/week) in conjunction with a starting dose of 40mg of oral prednisone per day at Week 00 for two weeks which will be tapered down to zero 5 mg/week within nine weeks | Device: Granulocyte Monocyte Apheresis (GMA-Apheresis)<br>* GMA Apheresis will be performed in a once per week during seven weeks only in experimental arm. Each apheresis will last 60 minutes at a blood flow rate of 30 ml/min.<br>|
| Active Comparator: 2<br>Treatment with starting dose of 40mg of oral prednisone per day at Week 00 for two weeks and tapered down to zero 5 mg/week within nine weeks | Device: Granulocyte Monocyte Apheresis (GMA-Apheresis)<br>* GMA Apheresis will be performed in a once per week during seven weeks only in experimental arm. Each apheresis will last 60 minutes at a blood flow rate of 30 ml/min.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients in steroid free clinical remission defined by Mayo Score less or equal to 2 with no individual subscore >1 at week 24 |  | week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Steroid free remission (assessed by Mayo score) |  | Week 12 | 
| Response at week 12 and 24 (defined by a decrease in Mayo Score > or = to 3 points |  | week 12 and week 24 | 
| Acute Phase reactants change at all lab analysis |  | 24 weeks | 
| Rescue therapy requirements (new courses of steroids, cyclosporine, infliximab, or surgery) during study period |  | 24 weeks | 
| Time to relapse |  | 24 weeks | 
| · Clinical response according to the activity indexes Truelove & Witts, Powell Tuc, Rachmiliewitz (Clinical Activity Index), Lichtiger (Modified Truelove & Witts Severity Index), Walmsley (Simple Clinical Colitis Index |  | 24 weeks | 
| Clinical remission and response at weeks 12 and 24 analysed according to concomitant use of immunosupressants |  | 24 weeks | 
| Adverse events |  | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ulcerative Colitis, Inflammatory Bowel disease, Steroid dependent, Adacolumn, Apheresis, Granulocyte Monocyte apheresis, GMA apheresis, Granulocytapheresis