Clinical trial NCT00702611: Efficacy Study of Granulocytapheresis Plus Steroids vs Steroids Alone in Active Steroid Dependant Ulcerative Colitis
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Ulcerative Colitis
Keywords: Ulcerative Colitis
Inflammatory Bowel disease
Steroid dependent
Adacolumn
Apheresis
Granulocyte Monocyte apheresis
GMA apheresis
Granulocytapheresis
Lead sponsor: Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa
Sponsor class: OTHER
First posted: 2008-06-20
Enrollment: 133
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: 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
timeFrame: week 24
Secondary outcomes:
measure: Steroid free remission (assessed by Mayo score)
timeFrame: Week 12
measure: Response at week 12 and 24 (defined by a decrease in Mayo Score > or = to 3 points
timeFrame: week 12 and week 24
measure: Acute Phase reactants change at all lab analysis
timeFrame: 24 weeks
measure: Rescue therapy requirements (new courses of steroids, cyclosporine, infliximab, or surgery) during study period
timeFrame: 24 weeks
measure: Time to relapse
timeFrame: 24 weeks
measure: · 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
timeFrame: 24 weeks
measure: Clinical remission and response at weeks 12 and 24 analysed according to concomitant use of immunosupressants
timeFrame: 24 weeks
measure: Adverse events
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Essen
country: Germany
facility: Katolische Kliniken Ruhrhalbinsel
city: Frankfurt
country: Germany
facility: Markus-Krankenhaus
city: Bari
country: Italy
facility: Policlinico di Bari
city: Belluno
country: Italy
facility: Ospedale di Belluno
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria di Careggi
city: Forli
country: Italy
facility: L'Azienda Unità Sanitaria Locale di Forlì
city: Milan
country: Italy
facility: Istituto Policlinico S. Donato
city: Padova
country: Italy
facility: Policlinico di Padova
city: Roma
country: Italy
facility: Policlinico Universitario Tor Vergata
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: San Giovanni Rotondo
country: Italy
facility: Casa Sollievo della Sofferenza, Istituto di Ricovero e Cura a Carattere Scientifico, Opera di San Pio da Pietrelcina
city: Coimbra
country: Portugal
facility: Hospital da Universidade de Coimbra
city: Lisboa
country: Portugal
facility: Hospital Santa Maria
city: Lisboa
country: Portugal
facility: Instituto Portuges Oncologia Lisboa Francisco Gentil
city: Porto
country: Portugal
facility: Hospital Geral Santo Antonio
city: Porto
country: Portugal
facility: Hospital de Sao Joao
city: Setubal
country: Portugal
facility: Hospital de Sao Bernardo
city: Viseu
country: Portugal
facility: Hospital Sao Teotonio
city: Santiago de Compostela
country: Spain
facility: Complejo Hspitalario Universitario Santiago de Compostela
state: A Coruña
city: Elche
country: Spain
facility: Hospital General de Elche
state: Alicante
city: Córdoba
country: Spain
facility: Complejo Hospitalario Reina Sofía
state: Andalucía
city: Oviedo
country: Spain
facility: Hospital Central de Asturias
state: Asturias
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Barcelona
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge
state: Barcelona
city: Terrassa
country: Spain
facility: Hospital Mutua de Terrassa
state: Barcelona
city: Galdakao
country: Spain
facility: Hospital de Galdakano
state: Bilbao
city: Palma de Mallorca
country: Spain
facility: Hospital Son Dureta
state: Comunidad Balear
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario Juan Canalejo
state: Galicia
city: San Sebastian
country: Spain
facility: Hospital de Donostia
state: Guipuzcoa
city: Pamplona
country: Spain
facility: Hospital de Navarra
state: Navarra
city: Sagunto
country: Spain
facility: Hospital Puerto de Sagunto
state: Valencia
city: Albacete
country: Spain
facility: Complejo Universitario de Albacete
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Girona
country: Spain
facility: Hospital Josep Trueta
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Insular de Las Palmas
city: Leon
country: Spain
facility: Hospital de Leon
city: Madrid
country: Spain
facility: Clínica Puerta de Hierro
city: Madrid
country: Spain
facility: Hospital Fundación de Alcorcón
city: Madrid
country: Spain
facility: Hospital Universitario Clínico de San Carlos
city: Murcia
country: Spain
facility: Hospital Virgen de la Arrixaca
city: Málaga
country: Spain
facility: Hospital Costa del Sol
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital de Manises
city: Vigo
country: Spain
facility: Hospital do Meixoeiro
Study officials:
affiliation: Hospital Clinic i Provincial Barcelona
name: Julian Panes, Ph D
role: PRINCIPAL_INVESTIGATOR
affiliation: Geteccu President
name: Joaquín Hinojosa, Ph D
role: STUDY_CHAIR
affiliation: Hospital Son Dureta Palma de Mallorca
name: Daniel Ginard, MD
role: STUDY_DIRECTOR
affiliation: Germans Trias i Pujol Hospital
name: Eugeni Domenech, Ph D
role: PRINCIPAL_INVESTIGATOR
affiliation: Otsuka Pharmaceutical S.A.
name: Raul Lafuente, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital San Joao, Oporto
name: Fernando Magro, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Casa Sollievo de la Sofferenza, Italy
name: Vito Annesse, Ph D
role: PRINCIPAL_INVESTIGATOR
References: