Crohn´s DiseasePhase 3APPRECIANCT01564823
Adalimumab on Preventing Post-chirurgic Recurrence on Crohn´s Disease
A Phase 3 study testing Metronidazole, Azathioprine and Adalimumab in people with Crohn´s Disease, run by Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa at 22 sites in Spain.
Trial summary
The present study objective is evaluate Adalimumab efficacy versus Azathioprine efficacy on prevention of endoscopic recurrence (Rutgeerts Index= 2b, 3 or 4) in Crohn´s Disease patients after 52 weeks of treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Crohn´s Disease
- What is being tested?
- Metronidazole, Azathioprine and Adalimumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 86 participants
- Where
- 22 sitesSpain
- Study dates
- Jun 2012to Jan 2015
- Phase
- Phase 3
- 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 of age at the time of signing informed consent.
- Patients with Crohn's disease who have undergone an ileocecal/ileocolic resection (L1 or L3). The study and the treatment must be initiated within the two first weeks after the resection (+/- 5 days).
- Patients with surgical reconstruction by ileocolic anastomosis.
- Women of childbearing age must not be breastfeeding and must have a negative urine pregnancy test and must agree to use contraceptive methods with a <1% failure rate (e.g., sexual abstinence, oral contraceptives, double barrier methods, intrauterine devices), unless they only have one partner who is sterile.
- Patients who have signed and dated the informed consent form before performing any specific screening study procedure.
Who cannot join
- Resection that requieres Temporal ileostomy.
- Urgency resection which doesn´t permit the initial assessment protocol completion.
- Resection due to inactive short indolent stenosis (<10 cm).
- Resection with mucosal macroscopic residual disease in anastomosis.
- Previous intolerance or adverse reaction (moderate or severe) to adalimumab or azathioprine.
- Any contraindications or unwillingness to perform the scheduled colonoscopies or resonances.
Show all 10Show fewer
- Contraindications to Adalimumab treatment, among which the following are included: active tuberculosis, severe infections such as sepsis or opportunistic infections, moderate or severe heart failure (NYHA class III or IV), central nervous system demyelinating diseases, history of malignant neoplasm or autoimmune diseases.
- Severe associated Extraintestinal manifestations.
- Previous postoperative recurrence prevention treatments with adalimumab, asathiprine o mercaptopurine which resulted in failure.
- Any other disease or patient condition that according to investigator criteria, inadequates patient´s participation in the study.
Trial locations and contacts
22 sites in 1 country.
22 sites in 1 country
Spain22 sites
Hospital Germans Trias i Pujol
Badalona, Barcelona
Hospital de Bellvitge
Barcelona, Barcelona
Hospital del Mar
Barcelona, Barcelona
Hospital Reina Sofía
Córdoba, Córdoba
Hospital Arquitecto Marcide
Ferrol, La Coruña
Hospital de Fuenlabrada
Fuenlabrada, Madrid
Hospital General Dr. Negrín
Las Palmas de Gran Canaria, Canary Islands
Hospital Clínico San Carlos
Madrid, Madrid
Hospital Doce de Octubre
Madrid, Madrid
Hospital Gregorio Marañón
Madrid, Madrid
Hospital La Paz
Madrid, Madrid
Hospital La Princesa
Madrid, Madrid
Hospital Puerta de Hierro
Madrid, Madrid
Hospital Ramón y Cajal
Madrid, Madrid
Hospital de Manises
Manises, Valencia
Hospital Puerto Real
Puerto Real, Cádiz
Hospital Parc Tauli
Sabadell, Barcelona
Hospital Virgen de la Macarena
Seville, Sevilla
Hospital Mutua de Terrasa
Terrassa, Barcelona
Hospital Universitari i Policlinic La Fe
Valencia, Valencia, 46026
Hospital Clínico
Valencia, Valencia
Hospital Río Hortega
Valladolid, Valladolid
About this study
Official title: Adalimumab on Preventing Postoperative Recurrence of Crohn's Disease
The present study objective is evaluate Adalimumab efficacy versus Azathioprine efficacy on prevention of endoscopic recurrence (Rutgeerts Index= 2b, 3 or 4) in Crohn´s Disease patients after 52 weeks of treatment.
- Conditions
- Crohn´s Disease
- Being tested
- Metronidazole, Azathioprine, Adalimumab
- Keywords
- Crohn´s disease, Metronidazole, Azathioprine, Adalimumab, post-chirurgic recurrence
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetronidazoleDrug
Also called Flagyl (Metronidazole)
Metronidazole: 250 mg/8h. 3 months.
MetronidazoleDrug
Also called Flagyl (Metronidazole)
Metronidazole 250 mg/8h 3 months
AzathioprineDrug
Also called Imurel (Azathioprine)
Azathioprine: 2.5 mg/kg of weight/day. 3 months.
AdalimumabDrug
Also called Humira (Adalimumab)
Adalimumab 160 mg then 80 mg. After 2 wk: 40 mg as maintenance.
| Study group | Role | What they receive |
|---|---|---|
| Metronidazole + Azathioprine. | Experimental | Metronidazole, oral intake. 250 mg/8h. 3 months. Azathioprine, 2.5 mg/weight kg/day, oral intake. All study. Receives: Drug: Metronidazole; Drug: Azathioprine |
| Metronidazole + Adalimumab | Active comparator | Metronidazole Oral Intake. 250 mg/8h. During 3 months. Adalimumab Subcutaneous 160 mg and 80 mg 2wk. Then 40 mg during 2wk as maintenance. Receives: Drug: Metronidazole; Drug: Adalimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of endoscopic recurrences
Evaluation of the effectiveness on prevention of endoscopic recurrence evaluated as changes in the Rutgeerts Index.
Measured: 52 weeks after the begin of the study
Secondary outcomes (10)
Number of Crohns´disease remission
% of patients showing clinical remission after 24 and 52 weeks of adalimumab vs azathioprin treatment
Measured: 24 weeks
Number of postsurgical recurrences
Evaluation of the Adalimumab efficiency on preventing postsurgical recurrence with Magnetic Resonance Enterography
Measured: 52 week
number of hospitalized patients
Comparing hospitalization percentage in patients using adalimumab or azathioprin after 52 weeks of treatment
Measured: 52 weeks
Concentration of activity markers
Evaluating changes in markers such as reactive c-protein, variable surface glycoprotein , faecal calprotectin, etc.
Measured: 24 weeks
Number of surgeries
Comparing % of patients who needs surgery on Adalimumab vs Azatioprine
Measured: Until 52 week
SIBDQ and EuroQOL indexes
Quality of life
Measured: 24 Weeks
Number of Adverse event reports
Comparison of safety of Adalimumab versus Azatioprine.
Measured: 52 weeks
Number of Crohns´disease remission
% of patients showing clinical remission after 24 and 52 weeks of adalimumab vs azatioprine treatment
Measured: 52 weeks
Concentration of activity markers
Evaluating changes in markers such as reactive c-protein, VSG, faecal calprotectine, etc
Measured: 52 weeks
SIBDQ and EuroQOL indexes
Quality of life
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2012 (estimated)
- Study startJun 2012
- Primary completionJan 2015
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Crohn´s DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa
- Sponsor type
- University, hospital or other
- Collaborators
- Effice Servicios Para la Investigacion S.L.
- Responsible party
- Sponsor
- Investigators
- Pilar Nos, MD, Principal investigator, Hospital Universitari i Politecnic La Fe (Valencia, Spain)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01564823
- Sponsor's protocol ID
- APPRECIA
- Acronym
- APPRECIA
- Status last verified
- Mar 2015
- First submitted
- 31 Jan 2012
- Last updated
- 17 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Lopez-Sanroman A, Vera-Mendoza I, Domenech E, Taxonera C, Vega Ruiz V, Marin-Jimenez I, Guardiola J, Castro L, Esteve M, Iglesias E, Ceballos D, Martinez-Montiel P, Gisbert JP, Minguez M, Echarri A, Calvet X, Barrio J, Hinojosa J, Martin-Arranz MD, Marquez-Mosquera L, Bermejo F, Rimola J, Pons V, Nos P; Spanish GETECCU group [APPRECIA study]. Adalimumab vs Azathioprine in the Prevention of Postoperative Crohn's Disease Recurrence. A GETECCU Randomised Trial. J Crohns Colitis. 2017 Oct 27;11(11):1293-1301. doi: 10.1093/ecco-jcc/jjx051.
PubMed 28402454
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adalimumab on Preventing Postoperative Recurrence of Crohn's Disease
- ClinicalTrials.gov ID
- NCT01564823
- Acronym / sponsor ID
- APPRECIA / APPRECIA
- Conditions
- Crohn´s Disease
- Keywords
- Crohn´s disease, Metronidazole, Azathioprine, Adalimumab, post-chirurgic recurrence
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis UlcerosaUniversity, hospital or other
- Collaborators
- Effice Servicios Para la Investigacion S.L.
- Study start
- Jun 2012
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 28 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The present study objective is evaluate Adalimumab efficacy versus Azathioprine efficacy on prevention of endoscopic recurrence (Rutgeerts Index= 2b, 3 or 4) in Crohn´s Disease patients after 52 weeks of treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metronidazole + Azathioprine. | Experimental | Drug: Metronidazole, Drug: AzathioprineMetronidazole, oral intake. 250 mg/8h. 3 months. Azathioprine, 2.5 mg/weight kg/day, oral intake. All study. |
| Metronidazole + Adalimumab | Active comparator | Drug: Metronidazole, Drug: AdalimumabMetronidazole Oral Intake. 250 mg/8h. During 3 months. Adalimumab Subcutaneous 160 mg and 80 mg 2wk. Then 40 mg during 2wk as maintenance. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age ≥ 18 years of age at the time of signing informed consent.
- Patients with Crohn's disease who have undergone an ileocecal/ileocolic resection (L1 or L3). The study and the treatment must be initiated within the two first weeks after the resection (+/- 5 days).
- Patients with surgical reconstruction by ileocolic anastomosis.
- Women of childbearing age must not be breastfeeding and must have a negative urine pregnancy test and must agree to use contraceptive methods with a <1% failure rate (e.g., sexual abstinence, oral contraceptives, double barrier methods, intrauterine devices), unless they only have one partner who is sterile.
- Patients who have signed and dated the informed consent form before performing any specific screening study procedure.
Key exclusion criteria (10 listed)
- Resection that requieres Temporal ileostomy.
- Urgency resection which doesn´t permit the initial assessment protocol completion.
- Resection due to inactive short indolent stenosis (<10 cm).
- Resection with mucosal macroscopic residual disease in anastomosis.
- Previous intolerance or adverse reaction (moderate or severe) to adalimumab or azathioprine.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetronidazoleAlso: Flagyl (Metronidazole)Metronidazole: 250 mg/8h. 3 months. | Drug | Metronidazole + Azathioprine. |
| MetronidazoleAlso: Flagyl (Metronidazole)Metronidazole 250 mg/8h 3 months | Drug | Metronidazole + Adalimumab |
| AzathioprineAlso: Imurel (Azathioprine)Azathioprine: 2.5 mg/kg of weight/day. 3 months. | Drug | Metronidazole + Azathioprine. |
| AdalimumabAlso: Humira (Adalimumab)Adalimumab 160 mg then 80 mg. After 2 wk: 40 mg as maintenance. | Drug | Metronidazole + Adalimumab |
Primary outcome
Number of endoscopic recurrences
Time frame: 52 weeks after the begin of the study
Evaluation of the effectiveness on prevention of endoscopic recurrence evaluated as changes in the Rutgeerts Index.
10 secondary outcomes
Number of Crohns´disease remission
Time frame: 24 weeks
Number of postsurgical recurrences
Time frame: 52 week
number of hospitalized patients
Time frame: 52 weeks
Concentration of activity markers
Time frame: 24 weeks
Number of surgeries
Time frame: Until 52 week
SIBDQ and EuroQOL indexes
Time frame: 24 Weeks
Number of Adverse event reports
Time frame: 52 weeks
Number of Crohns´disease remission
Time frame: 52 weeks
Concentration of activity markers
Time frame: 52 weeks
SIBDQ and EuroQOL indexes
Time frame: 52 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2015.
- Derived from this study: PubMed 28402454Lopez-Sanroman A, Vera-Mendoza I, Domenech E, Taxonera C, Vega Ruiz V, Marin-Jimenez I, Guardiola J, Castro L, Esteve M, Iglesias E, Ceballos D, Martinez-Montiel P, Gisbert JP, Minguez M, Echarri A, Calvet X, Barrio J, Hinojosa J, Martin-Arranz MD, Marquez-Mosquera L, Bermejo F, Rimola J, Pons V, Nos P; Spanish GETECCU group [APPRECIA study]. Adalimumab vs Azathioprine in the Prevention of Postoperative Crohn's Disease Recurrence. A GETECCU Randomised Trial. J Crohns Colitis. 2017 Oct 27;11(11):1293-1301. doi: 10.1093/ecco-jcc/jjx051.
Related trials for Crohn´s Disease
Not yet recruitingPhase 1
An Open-label, DDI Study to Investigate the Effects of Duvakitug on the PK of Selected Cytochrome P450 Substrates
Ulcerative Colitis, Crohn's Disease
RecruitingObservational study
Longitudinal Immunophenotyping of Patients With Inflammatory Bowel Disease
Inflammatory Bowel Disease, Crohn's Disease
RecruitingObservational study
Ibd CAncer and seRious Infections in France (I-CARE 2)
IBD, Ulcerative Colitis
RecruitingObservational study
Characterization of Colorectal Dysplasic Lesions and Stratification of Their Evolving Risk in Inflammatory Bowel Disease Patients: a Prospective, Observational and Multicenter Study
Crohn Disease (CD), Colitis Ulcerative
Enrolling by invitationPhase 4
MOdel-Informed Precision Dosing of Ustekinumab and VEdolizumab in Inflammatory Bowel Disease
Inflammatory Bowel Diseases, Crohn Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pilar Nos, MD principal investigator
Hospital Universitari i Politecnic La Fe (Valencia, Spain)
22 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Metronidazole, Azathioprine and Adalimumab in people with Crohn´s Disease, run by Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa at 22 sites in Spain.
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 5 inclusion and 10 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 17 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in Spain. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Number of endoscopic recurrences (time frame: 52 weeks after the begin of the study). 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 NCT01564823, 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 17 Mar 2015.