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Ulcerative ColitisPhase 4ACTIVENCT02425852

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

A Phase 4 study testing Azathioprine, Infliximab and Prednisolone in people with Ulcerative Colitis, run by Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives at 16 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Ulcerative Colitis
What is being tested?
Azathioprine, Infliximab and Prednisolone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
65 participants
Where
16 sitesFrance
Study dates
Dec 2016to Jan 2023
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 3.2 EXCLUSION CRITERIA
  • 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.
  • 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 or positive interferon-gamma release assay (Quantiferon®)
  • 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.
  • Severe acute or chronic medical or psychiatric condition that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in judgement of the investigator, would make the subject inappropriate for entry in this study.
  • Subjects who, in the opinion of the investigator, will be uncooperative or unable to comply with study procedures.
  • Participation in another clinical trial.

Who cannot join

None listed.

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

France16 sites

  • Chu Besancon

    Besançon, 25030

  • CHU de CLERMONT FERRAND- Hopital Estain

    Clermont-Ferrand, 67000

  • APHP- Hopital BEAUJON

    Clichy, 92110

  • Hopital Louis Mourrier

    Colombes, 92700

  • Henri Mondor Hospital

    Créteil, 94010

  • Chu Kremlin Bicetre

    Le Kremlin-Bicêtre

  • CHRU Lille

    Lille

  • Chu Montpellier

    Montpellier, 34295

  • CHU de NICE- Hopital Archet 2

    Nice, 06200

  • Hopital Saint Louis

    Paris, 75010

  • Hopital St Antoine

    Paris, 75012

  • Hopital Saint Joseph

    Paris, 75014

  • CHU RENNES - Hopital Pontchaillou

    Rennes

  • Chu Rouen

    Rouen, 76031

  • Chu Saint Etienne

    Saint-Etienne, 42270

  • CHU NANCY - Hopital Brabois

    Vandœuvre-lès-Nancy, 54500

Other trials in France

About this study

Official title: A Randomized, Multicenter Open Label Study Comparing Early Administration of Azathioprine Plus Infliximab to Corticosteroids Plus Azathioprine for Acute Severe Colitis

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.

Read the detailed description

NUMBER OF PATIENTS : 73 patients in each group i.e. a total of 146patients. RECRUITMENT PERIOD : 36 months STUDY DURATION : 12 months

PRIMARY END POINT : Treatment failure is defined by:

  • Absence of steroid-free remission at W52 according to the total Mayo Disease Activity Index score
  • OR Absence of mucosal healing (Mayo endoscopic subscore 0-1)
  • OR Adverse event leading to treatment interruption
  • OR Colectomy
  • OR Death
  • OR Infliximab withdrawal in the combination therapy group OR Infliximab introduction in the azathioprine group SECONDARY END POINT: - Clinical response and remission at D7, W14 and W52 (according to Lichtiger score and total Mayo Disease Activity Index score)
  • Endoscopic and histological response
  • Mucosal healing (partial endoscopic Mayo subscore 0)
  • Colectomy rate
  • Adverse events rate
  • Fecal calprotectin
  • Health-economic outcome
Being tested
Azathioprine, Infliximab, Prednisolone, Hydrocortisone
Medical subject headings
Colitis, Ulcerative

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AzathioprineDrug

    Azathioprine alone versus Azathioprine and IFX

  • InfliximabDrug

  • PrednisoloneDrug

  • HydrocortisoneDrug

Study groups in NCT02425852
Study groupRoleWhat they receive
Combination therapy armActive comparatorInfliximab 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.
Receives: Drug: Azathioprine; Drug: Infliximab
Azathioprine armActive comparatorIntravenous 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.
Receives: Drug: Azathioprine; Drug: Prednisolone; Drug: Hydrocortisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Week 52

Secondary outcomes (1)

  1. Percentage of patients in clinical response at day 7

    Percentage of patients in clinical response at day 7 (Lichtiger Index score<10 with a decrease of at least 3 points compared with the baseline score) and at week 14 and week 52 (a decrease from baseline in the Mayo score ≥30% and ≥3 points, accompanied by either a rectal bleeding subscore of 0 or 1 or a decrease from baseline in the rectal bleeding subscore ≥1)

    • Percentage of patients in clinical remission at day 7, week 14 and week 52

    Measured: 7 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Apr 2015 (estimated)
  2. Study startDec 2016
  3. Primary completionJun 2022
  4. Study completionJan 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
65 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02425852
Sponsor's protocol ID
GETAID 2015-02
Acronym
ACTIVE
Status last verified
May 2023
First submitted
21 Apr 2015
Last updated
31 May 2023
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 39586616

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Azathioprine, Infliximab and Prednisolone in people with Ulcerative Colitis, run by Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives at 16 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of patients with treatment failure at week 52. (time frame: Week 52). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02425852, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 May 2023; AzTrials last refreshed its copy on 26 Oct 2026.

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