A Randomized, Multicenter Open Label Study Comparing Early Administration of Azathioprine Plus IFX to Steroids Plus Azathioprine for Acute Severe Colitis

NCT02425852 | Completed Phase 4

• 1 other identifier: GETAID 2015-02
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 16

Brief Summary

PHASE : IV TYPE OF STUDY : With direct benefit. DESCRIPTIVE : Multicentre, randomized, open label study. INCLUSION CRITERIA : Acute severe ulcerative colitis. OBJECTIVES : To compare the efficacy and safety of early administration of the combination therapy with infliximab and azathioprine with steroids and azathioprine in patients with acute severe ulcerative colitis treated with intravenous steroids. STUDY TREATMENTS : All patients : Intravenous steroids (0.8 mg/kg/day of methylprednisolone or equivalent) for 5 days. Combination therapy arm: Infliximab 5 mg/kg plus Azathioprine 2-2.5 mg/kg/day. Azathioprine arm: Steroids tapering for 3 months and Azathioprine 2-2.5 mg/kg/day.

Conditions

Ulcerative Colitis

Outcome Measures

Primary Outcomes (1)

• Percentage of patients with treatment failure at week 52.

  Failure is defined as: * absence of steroid-free remission (Total Mayo Disease Activity Index (DAI) score ≤ 2 with no individual subscore \> 1) * absence of mucosal healing (Endoscopic Mayo DAI subscore ≤ 1) * or severe adverse event leading to treatment interruption between day 0 and week 52 * or colectomy between day 0 and week 52 * or fatality between day 0 and week 52 * or infliximab withdrawal for failure and /or intolerance in the combination therapy group * or any biological agent introduction in the azathioprine group

  Week 52

Secondary Outcomes (1)

• Percentage of patients in clinical response at day 7

  7 days

Study Arms (2)

Combination therapy arm

ACTIVE COMPARATOR

Infliximab 5 mg/kg plus Azathioprine 2-2.5 mg/kg/day. Azathioprine will be introduced at day 5-7 and continued until week 52. Azathioprine dose regimen will be between 2 and 2.5 mg/kg/d, as close as possible to 2.5 mg/kg/d, or to 1.5 mg/kg/d for 6-mercaptopurine, in one daily intake.

Drug: Azathioprine; Drug: Infliximab

Azathioprine arm

ACTIVE COMPARATOR

Intravenous steroids will be continue until day 2. Then, steroid therapy will be orally administered at a dose of 40-60 mg/day ou 1 mg/kg/day prednisolone (or equivalent) and progressively reduced by 10mg step every week to 20mg per day, and then reduced by 5mg step every week until stopped. Hydrocortisone intake to prevent steroid weaning will be authorized until supradrenal function normalization. In patients with clinical response at day 7, Azathioprine will be introduced at day 5-7 and continued until week 52. Azathioprine dose regimen will be between 2 and 2.5 mg/kg/d, as close as possible of 2.5 mg/kg/d, or of 1.5 mg/kg/d for 6-mercaptopurine, in one daily intake.

Drug: Azathioprine; Drug: Prednisolone; Drug: Hydrocortisone

Interventions

Azathioprine DRUG

Azathioprine alone versus Azathioprine and IFX

Azathioprine arm; Combination therapy arm

Infliximab DRUG

Combination therapy arm

Prednisolone DRUG

Azathioprine arm

Hydrocortisone DRUG

Azathioprine arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 (Endoscopic Mayo subscore ≥ 2).
• Acute flare requiring hospitalization
• Severe acute flare of UC with a Lichtiger Index score \> 10 at Day -3
• 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.

You may not qualify if:

• Pregnant or breast-feeding woman.
• Previous treatment with infliximab.
• Treatment with adalimumab or golimumab within 8 weeks before randomization
• Treatment with vedolizumab within 4 weeks before randomization
• Azathioprine or 6-mercaptopurine treatment initiated more than 4 weeks before screening.
• Ongoing intravenous steroids for more than 96 hours at time of the screening
• Contraindication for anti-TNF therapy
• Indication for immediate surgery.
• History of colorectal dysplasia.
• Diagnosis of Crohn's disease or indeterminate colitis
• 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.

Sponsors & Collaborators

• Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives: lead

Study Sites (16)

Chu Besancon

Besançon, 25030, France

Location

CHU de CLERMONT FERRAND- Hopital Estain

Clermont-Ferrand, 67000, France

Location

APHP- Hopital BEAUJON

Clichy, 92110, France

Location

Hopital Louis Mourrier

Colombes, 92700, France

Location

Henri Mondor Hospital

Créteil, 94010, France

Location

Chu Kremlin Bicetre

Le Kremlin-Bicêtre, France

Location

CHRU Lille

Lille, France

Location

Chu Montpellier

Montpellier, 34295, France

Location

CHU de NICE- Hopital Archet 2

Nice, 06200, France

Location

Hopital Saint Louis

Paris, 75010, France

Location

Hopital St Antoine

Paris, 75012, France

Location

Hopital Saint Joseph

Paris, 75014, France

Location

CHU RENNES - Hopital Pontchaillou

Rennes, France

Location

Chu Rouen

Rouen, 76031, France

Location

Chu Saint Etienne

Saint-Etienne, 42270, France

Location

CHU NANCY - Hopital Brabois

Vandœuvre-lès-Nancy, 54500, France

Location

Related Publications (1)

• Amiot A, Seksik P, Meyer A, Stefanescu C, Wils P, Altwegg R, Vuitton L, Plastaras L, Nicolau A, Pereira B, Duveau N, Laharie D, Mboup B, Boualit M, Allez M, Rajca S, Chanteloup E, Bouguen G, Bazin T, Goutorbe F, Richard N, Moussata D, Vicaut E, Peyrin-Biroulet L. Top-down infliximab plus azathioprine versus azathioprine alone in patients with acute severe ulcerative colitis responsive to intravenous steroids: a parallel, open-label randomised controlled trial, the ACTIVE trial. Gut. 2025 Jan 17;74(2):197-205. doi: 10.1136/gutjnl-2024-333281.

  PMID: 39586616 DERIVED

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Azathioprine; Infliximab; Prednisolone; Hydrocortisone

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• Aurélien Amiot, MD

  Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives

  PRINCIPAL INVESTIGATOR

• Laurent Peyrin-Biroulet, MD, PhD

  Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2015
• First Posted: April 24, 2015
• Study Start: December 1, 2016
• Primary Completion: June 1, 2022
• Study Completion: January 1, 2023
• Last Updated: May 31, 2023

Record last verified: 2023-05

Locations

FR (16)