Efficacy Study of Granulocytapheresis Plus Steroids vs Steroids Alone in Active Steroid Dependant Ulcerative Colitis
- Conditions
- Ulcerative Colitis
- Interventions
- Device: Granulocyte Monocyte Apheresis (GMA-Apheresis)
- Registration Number
- NCT00702611
- Lead Sponsor
- Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 133
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 2 Granulocyte Monocyte Apheresis (GMA-Apheresis) 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 1 Granulocyte Monocyte Apheresis (GMA-Apheresis) 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
- Primary Outcome Measures
Name Time Method 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
Name Time Method · 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 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 Rescue therapy requirements (new courses of steroids, cyclosporine, infliximab, or surgery) during study period 24 weeks Time to relapse 24 weeks Clinical remission and response at weeks 12 and 24 analysed according to concomitant use of immunosupressants 24 weeks Adverse events 24 weeks Acute Phase reactants change at all lab analysis 24 weeks
Trial Locations
- Locations (48)
Hospital de Sao Bernardo
🇵🇹Setubal, Portugal
Hospital Universitario de Bellvitge
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Policlinico Universitario Tor Vergata
🇮🇹Roma, Italy
Casa Sollievo della Sofferenza, Istituto di Ricovero e Cura a Carattere Scientifico, Opera di San Pio da Pietrelcina
🇮🇹San Giovanni Rotondo, Italy
Ospedale di Belluno
🇮🇹Belluno, Italy
Hospital Son Dureta
🇪🇸Palma de Mallorca, Comunidad Balear, Spain
Hospital de Donostia
🇪🇸San Sebastian, Guipuzcoa, Spain
Clínica Puerta de Hierro
🇪🇸Madrid, Spain
Hospital da Universidade de Coimbra
🇵🇹Coimbra, Portugal
Policlinico di Bari
🇮🇹Bari, Italy
Azienda Ospedaliero-Universitaria di Careggi
🇮🇹Firenze, Italy
Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
Hospital de Leon
🇪🇸Leon, Spain
Hospital General Universitario de Alicante
🇪🇸Alicante, Spain
Hospital Josep Trueta
🇪🇸Girona, Spain
Hospital Geral Santo Antonio
🇵🇹Porto, Portugal
Policlinico di Padova
🇮🇹Padova, Italy
Markus-Krankenhaus
🇩🇪Frankfurt, Germany
Complejo Hospitalario Reina Sofía
🇪🇸Córdoba, Andalucía, Spain
Hospital Mutua de Terrassa
🇪🇸Terrassa, Barcelona, Spain
Hospital Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Katolische Kliniken Ruhrhalbinsel
🇩🇪Essen, Germany
Hospital de Galdakano
🇪🇸Galdakao, Bilbao, Spain
Hospital Puerto de Sagunto
🇪🇸Sagunto, Valencia, Spain
Complejo Universitario de Albacete
🇪🇸Albacete, Spain
Hospital Insular de Las Palmas
🇪🇸Las Palmas de Gran Canaria, Spain
Hospital Virgen de la Arrixaca
🇪🇸Murcia, Spain
Complejo Hospitalario Universitario Juan Canalejo
🇪🇸A Coruña, Galicia, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital Fundación de Alcorcón
🇪🇸Madrid, Spain
Hospital de Manises
🇪🇸Valencia, Spain
Hospital do Meixoeiro
🇪🇸Vigo, Spain
Medical University of Vienna
🇦🇹Vienna, Austria
L'Azienda Unità Sanitaria Locale di Forlì
🇮🇹Forli, Italy
Istituto Policlinico S. Donato
🇮🇹Milan, Italy
Instituto Portuges Oncologia Lisboa Francisco Gentil
🇵🇹Lisboa, Portugal
Hospital General de Elche
🇪🇸Elche, Alicante, Spain
Hospital Clinic i Provincial
🇪🇸Barcelona, Spain
Hospital Universitario Clínico de San Carlos
🇪🇸Madrid, Spain
Hospital Costa del Sol
🇪🇸Málaga, Spain
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
Hospital de Sao Joao
🇵🇹Porto, Portugal
Hospital Sao Teotonio
🇵🇹Viseu, Portugal
Hospital Santa Maria
🇵🇹Lisboa, Portugal
Complejo Hspitalario Universitario Santiago de Compostela
🇪🇸Santiago de Compostela, A Coruña, Spain
Hospital de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Central de Asturias
🇪🇸Oviedo, Asturias, Spain