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Study Comparing Cyclosporine With Infliximab in Steroid-refractory Severe Attacks of Ulcerative Colitis (CYSIF)

Primary Purpose

Ulcerative Colitis, Steroid Refractory

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
CYCLOSPORINE VS INFLIXIMAB
Sponsored by
Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ulcerative Colitis focused on measuring IBD, Ulcerative colitis, refractory to steroids

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age > 18 years.
  • Diagnosis of UC according to Lennard-Jones criteria (Appendix 1).
  • Endoscopically demonstrated colorectal lesions localized above the anal margin and extending at least up to 15cm proximally.
  • Severe acute flare of UC with a Lichtiger Index score > 10.
  • Refractoriness to high dose intravenous steroid therapy (≥ 0.8 mg/kg/d of methylprednisolone or equivalent) given for at least 5 days.
  • Adequate contraception for male or female subjects of childbearing potential, which will be continued throughout the study and at least 3 months after study termination.

Exclusion Criteria:

  • Pregnant or breast-feeding woman.
  • Previous treatment with cyclosporine or infliximab.
  • Azathioprine or 6-mercaptopurine treatment initiated more than 4 weeks before inclusion.
  • Indication for immediate surgery.
  • History of colorectal dysplasia.
  • Diagnosis of Crohn's disease.
  • Positive stool tests for amoebiasis and/or positive bacteriological culture for Salmonella, Shigella, Yersinia and Campylobacter and/or presence of Clostridium difficile B toxin in the stools.
  • Renal failure (creatininemia > upper limit of normal laboratory value).
  • Uncontrolled high blood pressure.
  • HIV, HBV viral infection (except the presence of positive anti-HBs antibodies) with serology not older than 3 months.
  • Uncontrolled bacterial or active viral infection.
  • Past medical history of malignant condition in the last 5 years (including leukaemia, lymphoma and myelodysplasia) except for baso-cellular cutaneous cancers.
  • Past medical history of myocardial infarction or heart failure.
  • Intradermal reaction to Tuberculin (Tubertest® 5 units) > 5mm.
  • Active tuberculosis
  • Untreated latent tuberculosis (see national recommendations. Appendix 2).
  • Abnormal blood count with polynuclear neutrophils < 1,500 G/L or white cells < 3,000, or platelets < 100,000 G/L.
  • Unexplained rise higher than 3 times the normal level for transaminases, alkaline phosphatases and/or higher than twice the normal level for bilirubin.
  • Non-compliant subjects.
  • Participation in another therapeutic study.

Sites / Locations

  • Hopital Erasme
  • Ulb - Clinique Saint Luc
  • Gent University Hospital
  • Leuven University Hospital
  • Helsinki University Hospital
  • Chu Amiens
  • Ch Avignon
  • Chu Besancon
  • CHU CAEN
  • Chu Clermont-Ferrand
  • Hopital Beaujon
  • Hopital Louis Mourrier
  • Hopital Henri Mondor
  • Hopital Bicetre
  • Chru Lille
  • Chu Marseille - Hopital Nord
  • Ch Le Raincy Montfermeil
  • Chu Nantes
  • CHU NICE
  • Hopital Lariboisiere
  • Hopital Saint Louis
  • Hopital St Antoine
  • Hopital Cochin
  • Hopital Georges Pompidou
  • Hopital Bichat
  • Institut Mutualiste Montsouris (Imm)
  • Hopital Haut Leveque
  • CHU LYON
  • Chu Reims
  • Chu Rennes
  • Chu Rouen
  • Chu Saint Etienne
  • Chu Strasbourg
  • Chu Toulouse
  • Chu Tours
  • Chu Nancy
  • Istituto Clinico Humanitas
  • Hospital Clinic
  • Hospital Mutua de Terressa
  • Hospital de la Princesa
  • Hospital Ramon Y Cajal

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

CICLO

INFLIXIMAB

Arm Description

Cyclosporine will be administered by continuous intravenous infusion at the initial dose regimen of 2mg/kg per day. After 24 hours of treatment, cyclosporine trough level will be measured and the dose adapted in order to obtain a cyclosporinaemia level between 150 and 250 ng/ml. Cyclosporinaemia will be reassessed every 48 hours for the duration of the continuous intravenous treatment.

INFLIXIMAB (REMICADE) Infliximab in the form of a freeze-dried compound is conditioned in 100mg vials. Treatment will first be reconstituted in 250ml isotonic saline solution, and slowly infused at the dose of 5mg/kg in 2 hours. In patients with clinical response at D7 (Lichtiger Index score < 10 for 2 consecutive days), two additional infliximab infusions will be administered at the dose of 5mg/kg at D14 and D42.

Outcomes

Primary Outcome Measures

% of patients with treatment failure defined as: absence of clinical response at D7 or absence of remission without steroids at D98 or relapse or severe adverse event leading to treatment interruption or colectomy or fatality between D0 and D98

Secondary Outcome Measures

% of patients in clinical response % patients in remission Lichtiger Index score MDAI score Time to discharge Endoscopic response colectomy rate Steroid dosage. Number of adverse events CMV infection

Full Information

First Posted
October 8, 2007
Last Updated
August 30, 2011
Sponsor
Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
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1. Study Identification

Unique Protocol Identification Number
NCT00542152
Brief Title
Study Comparing Cyclosporine With Infliximab in Steroid-refractory Severe Attacks of Ulcerative Colitis
Acronym
CYSIF
Official Title
A Randomized, Multicenter Open Label Study Comparing Cyclosporine With Infliximab in Steroid-refractory Severe Attacks of Ulcerative Colitis
Study Type
Interventional

2. Study Status

Record Verification Date
August 2011
Overall Recruitment Status
Completed
Study Start Date
June 2007 (undefined)
Primary Completion Date
June 2007 (Actual)
Study Completion Date
October 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
PHASE: IV TYPE OF STUDY: With direct benefit. DESCRIPTIVE: Multicenter, randomized, open label study. INCLUSION CRITERIA: Steroid-refractory ulcerative colitis. OBJECTIVES: To compare the efficacy of cyclosporine with infliximab in steroid- refractory attacks of ulcerative colitis. STUDY TREATMENTS:Cyclosporine 2mg/kg/day intravenous(IV)for 7days then Neoral 4mg/kg/day orally for 3 months. Infliximab 5mg/kg at Weeks 0, 2 and 6. NUMBER OF PATIENTS: 50 patients in each group i.e. a total of 100 patients. INCLUSION PERIOD: 24 months. STUDY DURATION: 27 months. MAIN EVALUATION CRITERIA: Clinical response at D7 according to the Lichtiger Index score AND Clinical Remission at D98 according to the Mayo Disease Activity Index score SECONDARY EVALUATION CRITERIA: Clinical remission at D98 (according to the Mayo Disease Activity Index score) Endoscopic response Colectomy rate Tolerance

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ulcerative Colitis, Steroid Refractory
Keywords
IBD, Ulcerative colitis, refractory to steroids

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
115 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CICLO
Arm Type
Active Comparator
Arm Description
Cyclosporine will be administered by continuous intravenous infusion at the initial dose regimen of 2mg/kg per day. After 24 hours of treatment, cyclosporine trough level will be measured and the dose adapted in order to obtain a cyclosporinaemia level between 150 and 250 ng/ml. Cyclosporinaemia will be reassessed every 48 hours for the duration of the continuous intravenous treatment.
Arm Title
INFLIXIMAB
Arm Type
Active Comparator
Arm Description
INFLIXIMAB (REMICADE) Infliximab in the form of a freeze-dried compound is conditioned in 100mg vials. Treatment will first be reconstituted in 250ml isotonic saline solution, and slowly infused at the dose of 5mg/kg in 2 hours. In patients with clinical response at D7 (Lichtiger Index score < 10 for 2 consecutive days), two additional infliximab infusions will be administered at the dose of 5mg/kg at D14 and D42.
Intervention Type
Drug
Intervention Name(s)
CYCLOSPORINE VS INFLIXIMAB
Other Intervention Name(s)
Cyclosporine (IV)= Brand Name = Sandinuum, Cyclosporine (PO)= brand name = Neoral, Infliximab (IV)= brand name= Remicade
Intervention Description
Cyclosporine 2mg/kg/day intravenous for 7 days then Neoral 4mg/kg/day orally for 3 months. Infliximab 5mg/kg at weeks 0, 2 and 6
Primary Outcome Measure Information:
Title
% of patients with treatment failure defined as: absence of clinical response at D7 or absence of remission without steroids at D98 or relapse or severe adverse event leading to treatment interruption or colectomy or fatality between D0 and D98
Time Frame
Day 7
Secondary Outcome Measure Information:
Title
% of patients in clinical response % patients in remission Lichtiger Index score MDAI score Time to discharge Endoscopic response colectomy rate Steroid dosage. Number of adverse events CMV infection
Time Frame
D98

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age > 18 years. Diagnosis of UC according to Lennard-Jones criteria (Appendix 1). Endoscopically demonstrated colorectal lesions localized above the anal margin and extending at least up to 15cm proximally. Severe acute flare of UC with a Lichtiger Index score > 10. Refractoriness to high dose intravenous steroid therapy (≥ 0.8 mg/kg/d of methylprednisolone or equivalent) given for at least 5 days. Adequate contraception for male or female subjects of childbearing potential, which will be continued throughout the study and at least 3 months after study termination. Exclusion Criteria: Pregnant or breast-feeding woman. Previous treatment with cyclosporine or infliximab. Azathioprine or 6-mercaptopurine treatment initiated more than 4 weeks before inclusion. Indication for immediate surgery. History of colorectal dysplasia. Diagnosis of Crohn's disease. Positive stool tests for amoebiasis and/or positive bacteriological culture for Salmonella, Shigella, Yersinia and Campylobacter and/or presence of Clostridium difficile B toxin in the stools. Renal failure (creatininemia > upper limit of normal laboratory value). Uncontrolled high blood pressure. HIV, HBV viral infection (except the presence of positive anti-HBs antibodies) with serology not older than 3 months. Uncontrolled bacterial or active viral infection. Past medical history of malignant condition in the last 5 years (including leukaemia, lymphoma and myelodysplasia) except for baso-cellular cutaneous cancers. Past medical history of myocardial infarction or heart failure. Intradermal reaction to Tuberculin (Tubertest® 5 units) > 5mm. Active tuberculosis Untreated latent tuberculosis (see national recommendations. Appendix 2). Abnormal blood count with polynuclear neutrophils < 1,500 G/L or white cells < 3,000, or platelets < 100,000 G/L. Unexplained rise higher than 3 times the normal level for transaminases, alkaline phosphatases and/or higher than twice the normal level for bilirubin. Non-compliant subjects. Participation in another therapeutic study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David LAHARIE, MD
Organizational Affiliation
Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hopital Erasme
City
Bruxelles
ZIP/Postal Code
1070
Country
Belgium
Facility Name
Ulb - Clinique Saint Luc
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Gent University Hospital
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Leuven University Hospital
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Helsinki University Hospital
City
Helsinki
ZIP/Postal Code
00029
Country
Finland
Facility Name
Chu Amiens
City
Amiens
ZIP/Postal Code
80054
Country
France
Facility Name
Ch Avignon
City
Avignon
ZIP/Postal Code
84000
Country
France
Facility Name
Chu Besancon
City
Besancon
ZIP/Postal Code
25030
Country
France
Facility Name
CHU CAEN
City
Caen
ZIP/Postal Code
14033
Country
France
Facility Name
Chu Clermont-Ferrand
City
Clermont-ferrand
ZIP/Postal Code
63003
Country
France
Facility Name
Hopital Beaujon
City
Clichy
ZIP/Postal Code
92110
Country
France
Facility Name
Hopital Louis Mourrier
City
Colombes
ZIP/Postal Code
92700
Country
France
Facility Name
Hopital Henri Mondor
City
Creteil
ZIP/Postal Code
94010
Country
France
Facility Name
Hopital Bicetre
City
Le Kremlin Bicetre
ZIP/Postal Code
94275
Country
France
Facility Name
Chru Lille
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Chu Marseille - Hopital Nord
City
Marseille
ZIP/Postal Code
13915
Country
France
Facility Name
Ch Le Raincy Montfermeil
City
Montfermeil
ZIP/Postal Code
93370
Country
France
Facility Name
Chu Nantes
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
CHU NICE
City
Nice
ZIP/Postal Code
06202
Country
France
Facility Name
Hopital Lariboisiere
City
Paris
ZIP/Postal Code
75010
Country
France
Facility Name
Hopital Saint Louis
City
Paris
ZIP/Postal Code
75010
Country
France
Facility Name
Hopital St Antoine
City
Paris
ZIP/Postal Code
75012
Country
France
Facility Name
Hopital Cochin
City
Paris
ZIP/Postal Code
75014
Country
France
Facility Name
Hopital Georges Pompidou
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Hopital Bichat
City
Paris
ZIP/Postal Code
75018
Country
France
Facility Name
Institut Mutualiste Montsouris (Imm)
City
Paris
ZIP/Postal Code
75674
Country
France
Facility Name
Hopital Haut Leveque
City
Pessac
ZIP/Postal Code
33604
Country
France
Facility Name
CHU LYON
City
Pierre Benite
ZIP/Postal Code
69495
Country
France
Facility Name
Chu Reims
City
Reims
Country
France
Facility Name
Chu Rennes
City
Rennes
ZIP/Postal Code
35033
Country
France
Facility Name
Chu Rouen
City
Rouen
ZIP/Postal Code
76031
Country
France
Facility Name
Chu Saint Etienne
City
St Etienne
ZIP/Postal Code
42270
Country
France
Facility Name
Chu Strasbourg
City
Strasbourg
ZIP/Postal Code
67091
Country
France
Facility Name
Chu Toulouse
City
Toulouse
ZIP/Postal Code
31403
Country
France
Facility Name
Chu Tours
City
Tours
ZIP/Postal Code
37044
Country
France
Facility Name
Chu Nancy
City
Vandoeuvre Les Nancy
ZIP/Postal Code
54500
Country
France
Facility Name
Istituto Clinico Humanitas
City
Milano
ZIP/Postal Code
20089
Country
Italy
Facility Name
Hospital Clinic
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital Mutua de Terressa
City
Barcelona
ZIP/Postal Code
08221
Country
Spain
Facility Name
Hospital de la Princesa
City
Madrid
ZIP/Postal Code
28006
Country
Spain
Facility Name
Hospital Ramon Y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
14084741
Citation
EDWARDS FC, TRUELOVE SC. THE COURSE AND PROGNOSIS OF ULCERATIVE COLITIS. Gut. 1963 Dec;4(4):299-315. doi: 10.1136/gut.4.4.299.
Results Reference
background
PubMed Identifier
82099
Citation
Truelove SC, Willoughby CP, Lee EG, Kettlewell MG. Further experience in the treatment of severe attacks of ulcerative colitis. Lancet. 1978 Nov 18;2(8099):1086-8. doi: 10.1016/s0140-6736(78)91816-0.
Results Reference
background
PubMed Identifier
11313301
Citation
D'Haens G, Lemmens L, Geboes K, Vandeputte L, Van Acker F, Mortelmans L, Peeters M, Vermeire S, Penninckx F, Nevens F, Hiele M, Rutgeerts P. Intravenous cyclosporine versus intravenous corticosteroids as single therapy for severe attacks of ulcerative colitis. Gastroenterology. 2001 May;120(6):1323-9. doi: 10.1053/gast.2001.23983.
Results Reference
background
PubMed Identifier
8196726
Citation
Lichtiger S, Present DH, Kornbluth A, Gelernt I, Bauer J, Galler G, Michelassi F, Hanauer S. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med. 1994 Jun 30;330(26):1841-5. doi: 10.1056/NEJM199406303302601.
Results Reference
background
PubMed Identifier
14517785
Citation
Van Assche G, D'Haens G, Noman M, Vermeire S, Hiele M, Asnong K, Arts J, D'Hoore A, Penninckx F, Rutgeerts P. Randomized, double-blind comparison of 4 mg/kg versus 2 mg/kg intravenous cyclosporine in severe ulcerative colitis. Gastroenterology. 2003 Oct;125(4):1025-31. doi: 10.1016/s0016-5085(03)01214-9.
Results Reference
background
PubMed Identifier
15168804
Citation
Arts J, D'Haens G, Zeegers M, Van Assche G, Hiele M, D'Hoore A, Penninckx F, Vermeire S, Rutgeerts P. Long-term outcome of treatment with intravenous cyclosporin in patients with severe ulcerative colitis. Inflamm Bowel Dis. 2004 Mar;10(2):73-8. doi: 10.1097/00054725-200403000-00002.
Results Reference
background
PubMed Identifier
11552900
Citation
Actis GC, Bresso F, Astegiano M, Demarchi B, Sapone N, Boscaglia C, Rizzetto M. Safety and efficacy of azathioprine in the maintenance of ciclosporin-induced remission of ulcerative colitis. Aliment Pharmacol Ther. 2001 Sep;15(9):1307-11. doi: 10.1046/j.1365-2036.2001.01019.x.
Results Reference
background
PubMed Identifier
10364029
Citation
Cohen RD, Stein R, Hanauer SB. Intravenous cyclosporin in ulcerative colitis: a five-year experience. Am J Gastroenterol. 1999 Jun;94(6):1587-92. doi: 10.1111/j.1572-0241.1999.01149.x.
Results Reference
background
PubMed Identifier
15972298
Citation
Ardizzone S, Maconi G, Russo A, Imbesi V, Colombo E, Bianchi Porro G. Randomised controlled trial of azathioprine and 5-aminosalicylic acid for treatment of steroid dependent ulcerative colitis. Gut. 2006 Jan;55(1):47-53. doi: 10.1136/gut.2005.068809. Epub 2005 Jun 21.
Results Reference
background
PubMed Identifier
15674937
Citation
Shibolet O, Regushevskaya E, Brezis M, Soares-Weiser K. Cyclosporine A for induction of remission in severe ulcerative colitis. Cochrane Database Syst Rev. 2005 Jan 25;(1):CD004277. doi: 10.1002/14651858.CD004277.pub2.
Results Reference
background
PubMed Identifier
15940615
Citation
Jarnerot G, Hertervig E, Friis-Liby I, Blomquist L, Karlen P, Granno C, Vilien M, Strom M, Danielsson A, Verbaan H, Hellstrom PM, Magnuson A, Curman B. Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study. Gastroenterology. 2005 Jun;128(7):1805-11. doi: 10.1053/j.gastro.2005.03.003.
Results Reference
background
PubMed Identifier
12385442
Citation
Su C, Salzberg BA, Lewis JD, Deren JJ, Kornbluth A, Katzka DA, Stein RB, Adler DR, Lichtenstein GR. Efficacy of anti-tumor necrosis factor therapy in patients with ulcerative colitis. Am J Gastroenterol. 2002 Oct;97(10):2577-84. doi: 10.1111/j.1572-0241.2002.06026.x.
Results Reference
background
PubMed Identifier
12869077
Citation
Gornet JM, Couve S, Hassani Z, Delchier JC, Marteau P, Cosnes J, Bouhnik Y, Dupas JL, Modigliani R, Taillard F, Lemann M. Infliximab for refractory ulcerative colitis or indeterminate colitis: an open-label multicentre study. Aliment Pharmacol Ther. 2003 Jul 15;18(2):175-81. doi: 10.1046/j.1365-2036.2003.01686.x.
Results Reference
background
PubMed Identifier
15638237
Citation
Kohn A, Prantera C, Pera A, Cosintino R, Sostegni R, Daperno M. Infliximab in the treatment of severe ulcerative colitis: a follow-up study. Eur Rev Med Pharmacol Sci. 2004 Sep-Oct;8(5):235-7.
Results Reference
background
PubMed Identifier
15735427
Citation
Eidelwein AP, Cuffari C, Abadom V, Oliva-Hemker M. Infliximab efficacy in pediatric ulcerative colitis. Inflamm Bowel Dis. 2005 Mar;11(3):213-8. doi: 10.1097/01.mib.0000160803.44449.a5.
Results Reference
background
PubMed Identifier
16339095
Citation
Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005 Dec 8;353(23):2462-76. doi: 10.1056/NEJMoa050516. Erratum In: N Engl J Med. 2006 May 18;354(20):2200.
Results Reference
background
PubMed Identifier
28053054
Citation
Laharie D, Bourreille A, Branche J, Allez M, Bouhnik Y, Filippi J, Zerbib F, Savoye G, Vuitton L, Moreau J, Amiot A, Cosnes J, Ricart E, Dewit O, Lopez-Sanroman A, Fumery M, Carbonnel F, Bommelaer G, Coffin B, Roblin X, van Assche G, Esteve M, Farkkila M, Gisbert JP, Marteau P, Nahon S, de Vos M, Lambert J, Mary JY, Louis E; Groupe d'Etudes Therapeutiques des Affections Inflammatoires Digestives. Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab. Gut. 2018 Feb;67(2):237-243. doi: 10.1136/gutjnl-2016-313060. Epub 2017 Jan 4.
Results Reference
derived
PubMed Identifier
23063316
Citation
Laharie D, Bourreille A, Branche J, Allez M, Bouhnik Y, Filippi J, Zerbib F, Savoye G, Nachury M, Moreau J, Delchier JC, Cosnes J, Ricart E, Dewit O, Lopez-Sanroman A, Dupas JL, Carbonnel F, Bommelaer G, Coffin B, Roblin X, Van Assche G, Esteve M, Farkkila M, Gisbert JP, Marteau P, Nahon S, de Vos M, Franchimont D, Mary JY, Colombel JF, Lemann M; Groupe d'Etudes Therapeutiques des Affections Inflammatoires Digestives. Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomised controlled trial. Lancet. 2012 Dec 1;380(9857):1909-15. doi: 10.1016/S0140-6736(12)61084-8. Epub 2012 Oct 10.
Results Reference
derived
Links:
URL
http://www.getaid.org
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Study Comparing Cyclosporine With Infliximab in Steroid-refractory Severe Attacks of Ulcerative Colitis

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