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

Condition(s) targeted: Ulcerative Colitis

Intervention: Granulocyte Monocyte Apheresis (GMA-Apheresis) (Device)

Phase: Phase 4

Status: Recruiting

Sponsored by: Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa

Official(s) and/or principal investigator(s):
Julian Panes, Ph D, Principal Investigator, Affiliation: Hospital Clinic i Provincial Barcelona
Joaquín Hinojosa, Ph D, Study Chair, Affiliation: Geteccu President
Daniel Ginard, MD, Study Director, Affiliation: Hospital Son Dureta Palma de Mallorca
Eugeni Domenech, Ph D, Principal Investigator, Affiliation: Hospital Germans Trias i Pujol, Badalona
Raul Lafuente, MD, Principal Investigator, Affiliation: Otsuka Pharmaceutical S.A.
Fernando Magro, PhD, Principal Investigator, Affiliation: Hospital San Joao, Oporto
Vito Annesse, Ph D, Principal Investigator, Affiliation: Casa Sollievo de la Sofferenza, Italy

Overall contact:
Daniel Ginard, MD, Phone: +34971175244, Email: geteccu.aticca@gmail.com

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

Official title: 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

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Primary outcome: 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

Secondary outcome:

Steroid free remission (assessed by Mayo score)

Response at week 12 and 24 (defined by a decrease in Mayo Score > or = to 3 points

Acute Phase reactants change at all lab analysis

Rescue therapy requirements (new courses of steroids, cyclosporine, infliximab, or surgery) during study period

Time to relapse

· 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

Clinical remission and response at weeks 12 and 24 analysed according to concomitant use of immunosupressants

Adverse events

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.

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

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

Daniel Ginard, MD, Phone: +34971175244, Email: geteccu.aticca@gmail.com

Casa Sollievo della Sofferenza, Istituto di Ricovero e Cura a Carattere Scientifico, Opera di San Pio da Pietrelcina, San Giovanni Rotondo, Italy; Not yet recruiting
Phone: 0039 0882 4101
Vito Annese, MD, Principal Investigator

Istituto Policlinico S. Donato, Milan, Italy; Not yet recruiting
Maurizio Vecchi, MD PhD, Principal Investigator

Policlinico S.Orsola Malpighi, Bologna, Italy; Not yet recruiting
Massimo Campieri, MD, Principal Investigator

Policlinico Universitario Tor Vergata, Roma, Italy; Not yet recruiting
Francesco Pallone, Principal Investigator

Ospedale Luigi SaccoSacco, Milano, Italy; Not yet recruiting
Bianchi Porro, MD PhD, Principal Investigator

Azienda Ospedaliera Ospedali Riuniti di Ancona, Università Politecnica delle Marche, Ancona, Italy; Not yet recruiting
Antonio Bennedetti, MD, Principal Investigator

Policlinico di Bari, Bari, Italy; Not yet recruiting
Antonio Francavilla, MD, Principal Investigator

Policlinico di Padova, Padova, Italy; Not yet recruiting
Giancarlo Sturniolo, MD, Principal Investigator

Ospedale Belcolle, Viterbo, Italy; Not yet recruiting
Marcello Anti, MD, Principal Investigator

Ospedale di Belluno, Belluno, Italy; Not yet recruiting

Hospital de Sao Joao, Porto 4200-319, Portugal; Not yet recruiting
Fernando Magro, MD PhD, Principal Investigator

Hospital Geral Santo Antonio, Porto 4099-001, Portugal; Not yet recruiting
Paula Lago, MD, Principal Investigator

Hospital da Universidade de Coimbra, Coimbra 3000-075, Portugal; Not yet recruiting
Francisco Portela, MD, Principal Investigator

Hospital Garcia de Horta, Almada, Portugal; Not yet recruiting
Joao Freitas, MD, Principal Investigator

Hospital de Sao Bernardo, Setubal, Portugal; Not yet recruiting
Isabelle Cremers, MD, Principal Investigator

Hospital Fernando Fonseca-Amadora Sintra, Amadora, Portugal; Not yet recruiting
Joao de Deus, MD, Principal Investigator

Hospital Santa Maria, Lisboa, Portugal; Not yet recruiting
Lurdes Tavares, MD, Principal Investigator

Instituto Portuges Oncologia Lisboa Francisco Gentil, Lisboa, Portugal; Not yet recruiting
Marilia Cravo, MD, Principal Investigator

Hospital Sao Teotonio, Viseu, Portugal; Not yet recruiting
Paula Ministro, MD, Principal Investigator

Hospital Morales Messeguer, Murcia, Spain; Recruiting
Emilio Torrella, MD, Principal Investigator

Hospital Virgen de la Arrixaca, Murcia, Spain; Recruiting
Hortensia Salama, MD, Principal Investigator

Hospital Universitario Virgen del Rocío, Sevilla, Spain; Recruiting
José M Herrera, MD, Principal Investigator

Hospital Insular de Las Palmas, Las Palmas de Gran Canaria, Spain; Recruiting
Angel Sierra, MD, Principal Investigator

Hospital Dr. Negrin, Las Palmas de Gran Canaria, Spain; Recruiting
Daniel Ceballos, MD, Principal Investigator

Hospital Costa del Sol, Málaga, Spain; Recruiting
Francisco Fernández, MD, Principal Investigator

Hospital Infanta Cristina, Badajoz, Spain; Not yet recruiting

Hospital Universitario Virgen de las Nieves, Granada 18014, Spain; Not yet recruiting

Hospital General Universitario de Alicante, Alicante, Spain; Recruiting
Ana Gutiérrez, MD, Principal Investigator

Hospital Clinic i Provincial, Barcelona, Spain; Recruiting
Julian Panes, Ph D, Phone: +34932275418, Ext: 2779, Email: jpanes@clinic.ub.es
Julian Panes, MD Ph D, Principal Investigator

Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Recruiting
Esther García-Planella, MD, Principal Investigator

Hospital del Mar, Barcelona, Spain; Recruiting
Montserrat Andreu, MD, Principal Investigator

Hospital Virgen de La Luz, Cuenca, Spain; Active, not recruiting

Hospital de Leon, Leon, Spain; Recruiting
Fernando Muñoz, MD, Principal Investigator

Hospital Universitario Gregorio Marañón, Madrid, Spain; Recruiting
Ignacio Marín, MD, Principal Investigator

Hospital Universitario Ramon y Cajal, Madrid, Spain; Active, not recruiting

Hospital Fundación de Alcorcón, Madrid, Spain; Recruiting
José Pérez-Calle, MD, Principal Investigator

Clínica Puerta de Hierro, Madrid, Spain; Recruiting
Luis Abreu, MD PhD, Principal Investigator

Hospital Universitario Clínico de San Carlos, Madrid, Spain; Recruiting
Carlos Taxonera, MD, Principal Investigator

Hospital De La Princesa, Madrid, Spain; Recruiting
Javier Pérez-Gisbert, MD PhD, Principal Investigator

Hospital 12 de Octubre, Madrid, Spain; Recruiting
Pilar Martínez -Montiel, MD PhD, Principal Investigator

Hospital Universitari La Fe, Valencia, Spain; Active, not recruiting

Hospital Clínico de Valencia, Valencia, Spain; Recruiting
Miguel Mínguez, MD, Principal Investigator

Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain; Recruiting
Fernando Gomollón, MD. PhD, Principal Investigator

Complejo Hspitalario Universitario Santiago de Compostela, Santiago de Compostela, A Coruña, Spain; Active, not recruiting

Hospital General de Elche, Elche, Alicante, Spain; Active, not recruiting

Complejo Hospitalario Reina Sofía, Córdoba, Andalucía, Spain; Recruiting
Federico Gómez-Camacho, MD, Principal Investigator

Hospital Germans Trias i Pujol, Badalona, Barcelona 08916, Spain; Recruiting
Eugeni Domenech, MD, PhD, Phone: 934651200
Eugeni Domenech, MD PhD, Principal Investigator

Hospital Mutua de Terrassa, Terrassa, Barcelona 08221, Spain; Active, not recruiting

Hospital de Galdakano, Galdakao, Bilbao, Spain; Recruiting
Phone: 944007000
Jose Luis Cabriada, MD, Principal Investigator

Hospital General de Castellon, Castellon de la Plana, Castellón, Spain; Recruiting
Vicente Ripollés, MD PhD, Principal Investigator

Hospital Son Dureta, Palma de Mallorca, Comunidad Balear, Spain; Recruiting
Phone: 971175000
Daniel Ginard, MD, Principal Investigator

Complejo Hospitalario Universitario Juan Canalejo, A Coruña, Galicia, Spain; Recruiting
Benito González-Conde, MD, Principal Investigator

Hospital de Cabueñes, Gijon, Gijón, Spain; Recruiting
Phone: 985185000
Cristina Saro, MD,PhD, Principal Investigator

Hospital de Donostia, San Sebastian, Guipuzcoa, Spain; Recruiting
Phone: 943007060
Juan Ignacio Arenas, MD, Ph, Principal Investigator

Hospital de Navarra, Pamplona, Navarra, Spain; Recruiting
Antxon Arín Letamendía, MD PhD, Principal Investigator

Hospital Virgen del Camino, Pamplona, Navarra, Spain; Recruiting
Carlos Jiménez López, MD, Principal Investigator

Hospital Puerto de Sagunto, Sagunto, Valencia, Spain; Recruiting
Phone: 962659414
Joaquín Hinojosa, MD, PhD, Principal Investigator

Official web page of the GETECCU group

Starting date: June 2008
Ending date: March 2011
Last updated: June 19, 2008