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

Ulcerative Colitis Clinical Trial

— ATICCA  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00702611
• Other study ID #: Ada-UC-07-102
• Status: Terminated
• Phase: Phase 4
• First received: June 19, 2008
• Last updated: September 4, 2015
• Start date: June 2008
• Est. completion date: July 2013

Study information

• Verified date: September 2015
• Source: Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ministry of Health
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Terminated
• Enrollment: 133
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Device:
• Granulocyte Monocyte Apheresis (GMA-Apheresis)
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.

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna
Germany	Katolische Kliniken Ruhrhalbinsel	Essen
Germany	Markus-Krankenhaus	Frankfurt
Italy	Policlinico di Bari	Bari
Italy	Ospedale di Belluno	Belluno
Italy	Azienda Ospedaliero-Universitaria di Careggi	Firenze
Italy	L'Azienda Unità Sanitaria Locale di Forlì	Forli
Italy	Istituto Policlinico S. Donato	Milan
Italy	Policlinico di Padova	Padova
Italy	Policlinico Universitario Tor Vergata	Roma
Italy	Istituto Clinico Humanitas	Rozzano
Italy	Casa Sollievo della Sofferenza, Istituto di Ricovero e Cura a Carattere Scientifico, Opera di San Pio da Pietrelcina	San Giovanni Rotondo
Portugal	Hospital da Universidade de Coimbra	Coimbra
Portugal	Hospital Santa Maria	Lisboa
Portugal	Instituto Portuges Oncologia Lisboa Francisco Gentil	Lisboa
Portugal	Hospital de Sao Joao	Porto
Portugal	Hospital Geral Santo Antonio	Porto
Portugal	Hospital de Sao Bernardo	Setubal
Portugal	Hospital Sao Teotonio	Viseu
Spain	Complejo Hospitalario Universitario Juan Canalejo	A Coruña	Galicia
Spain	Complejo Universitario de Albacete	Albacete
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Clinic i Provincial	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Complejo Hospitalario Reina Sofía	Córdoba	Andalucía
Spain	Hospital General de Elche	Elche	Alicante
Spain	Hospital de Galdakano	Galdakao	Bilbao
Spain	Hospital Josep Trueta	Girona
Spain	Hospital Universitario de Bellvitge	Hospitalet de Llobregat	Barcelona
Spain	Hospital Insular de Las Palmas	Las Palmas de Gran Canaria
Spain	Hospital de Leon	Leon
Spain	Clínica Puerta de Hierro	Madrid
Spain	Hospital Fundación de Alcorcón	Madrid
Spain	Hospital Universitario Clínico de San Carlos	Madrid
Spain	Hospital Costa del Sol	Málaga
Spain	Hospital Virgen de la Arrixaca	Murcia
Spain	Hospital Central de Asturias	Oviedo	Asturias
Spain	Hospital Son Dureta	Palma de Mallorca	Comunidad Balear
Spain	Hospital de Navarra	Pamplona	Navarra
Spain	Hospital Puerto de Sagunto	Sagunto	Valencia
Spain	Hospital de Donostia	San Sebastian	Guipuzcoa
Spain	Complejo Hspitalario Universitario Santiago de Compostela	Santiago de Compostela	A Coruña
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Mutua de Terrassa	Terrassa	Barcelona
Spain	Hospital de Manises	Valencia
Spain	Hospital do Meixoeiro	Vigo

Sponsors (1)

Lead Sponsor	Collaborator
Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa

Countries where clinical trial is conducted

Austria,  Germany,  Italy,  Portugal,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Steroid free remission (assessed by Mayo score)		Week 12	No
Secondary	Response at week 12 and 24 (defined by a decrease in Mayo Score > or = to 3 points		week 12 and week 24	No
Secondary	Acute Phase reactants change at all lab analysis		24 weeks	No
Secondary	Rescue therapy requirements (new courses of steroids, cyclosporine, infliximab, or surgery) during study period		24 weeks	No
Secondary	Time to relapse		24 weeks	No
Secondary	· 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	No
Secondary	Clinical remission and response at weeks 12 and 24 analysed according to concomitant use of immunosupressants		24 weeks	No
Secondary	Adverse events		24 weeks	Yes

External Links

•   Official web page of the GETECCU group