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

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