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Adalimumab on Preventing Post-chirurgic Recurrence on Crohn´s Disease (APPRECIA)

Primary Purpose

Crohn´s Disease

Status
Completed
Phase
Phase 3
Locations
Spain
Study Type
Interventional
Intervention
Metronidazole
Metronidazole
Azathioprine
Adalimumab
Sponsored by
Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Crohn´s Disease focused on measuring Crohn´s disease, Metronidazole, Azathioprine, Adalimumab, post-chirurgic recurrence

Eligibility Criteria

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

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • 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.

Sites / Locations

  • Hospital Germans Trias i Pujol
  • Hospital Parc Tauli
  • Hospital Mutua de Terrasa
  • Hospital Puerto Real
  • Hospital General Dr. Negrín
  • Hospital Arquitecto Marcide
  • Hospital de Fuenlabrada
  • Hospital de Manises
  • Hospital de Bellvitge
  • Hospital del Mar
  • Hospital Reina Sofía
  • Hospital Clínico San Carlos
  • Hospital Doce de Octubre
  • Hospital Gregorio Marañón
  • Hospital La Paz
  • Hospital La Princesa
  • Hospital Puerta de Hierro
  • Hospital Ramón y Cajal
  • Hospital Virgen de la Macarena
  • Hospital Universitari i Policlinic La Fe
  • Hospital Clínico
  • Hospital Río Hortega

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Metronidazole + Azathioprine.

Metronidazole + Adalimumab

Arm Description

Metronidazole, oral intake. 250 mg/8h. 3 months. Azathioprine, 2.5 mg/weight kg/day, oral intake. All study.

Metronidazole Oral Intake. 250 mg/8h. During 3 months. Adalimumab Subcutaneous 160 mg and 80 mg 2wk. Then 40 mg during 2wk as maintenance.

Outcomes

Primary Outcome Measures

Number of endoscopic recurrences
Evaluation of the effectiveness on prevention of endoscopic recurrence evaluated as changes in the Rutgeerts Index.

Secondary Outcome Measures

Number of Crohns´disease remission
% of patients showing clinical remission after 24 and 52 weeks of adalimumab vs azathioprin treatment
Number of postsurgical recurrences
Evaluation of the Adalimumab efficiency on preventing postsurgical recurrence with Magnetic Resonance Enterography
number of hospitalized patients
Comparing hospitalization percentage in patients using adalimumab or azathioprin after 52 weeks of treatment
Concentration of activity markers
Evaluating changes in markers such as reactive c-protein, variable surface glycoprotein , faecal calprotectin, etc.
Number of surgeries
Comparing % of patients who needs surgery on Adalimumab vs Azatioprine
SIBDQ and EuroQOL indexes
Quality of life
Number of Adverse event reports
Comparison of safety of Adalimumab versus Azatioprine.
Number of Crohns´disease remission
% of patients showing clinical remission after 24 and 52 weeks of adalimumab vs azatioprine treatment
Concentration of activity markers
Evaluating changes in markers such as reactive c-protein, VSG, faecal calprotectine, etc
SIBDQ and EuroQOL indexes
Quality of life

Full Information

First Posted
January 31, 2012
Last Updated
March 15, 2015
Sponsor
Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa
Collaborators
Effice Servicios Para la Investigacion S.L.
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1. Study Identification

Unique Protocol Identification Number
NCT01564823
Brief Title
Adalimumab on Preventing Post-chirurgic Recurrence on Crohn´s Disease
Acronym
APPRECIA
Official Title
Adalimumab on Preventing Postoperative Recurrence of Crohn's Disease
Study Type
Interventional

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
June 2012 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
January 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa
Collaborators
Effice Servicios Para la Investigacion S.L.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn´s Disease
Keywords
Crohn´s disease, Metronidazole, Azathioprine, Adalimumab, post-chirurgic recurrence

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
86 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Metronidazole + Azathioprine.
Arm Type
Experimental
Arm Description
Metronidazole, oral intake. 250 mg/8h. 3 months. Azathioprine, 2.5 mg/weight kg/day, oral intake. All study.
Arm Title
Metronidazole + Adalimumab
Arm Type
Active Comparator
Arm Description
Metronidazole Oral Intake. 250 mg/8h. During 3 months. Adalimumab Subcutaneous 160 mg and 80 mg 2wk. Then 40 mg during 2wk as maintenance.
Intervention Type
Drug
Intervention Name(s)
Metronidazole
Other Intervention Name(s)
Flagyl (Metronidazole)
Intervention Description
Metronidazole: 250 mg/8h. 3 months.
Intervention Type
Drug
Intervention Name(s)
Metronidazole
Other Intervention Name(s)
Flagyl (Metronidazole)
Intervention Description
Metronidazole 250 mg/8h 3 months
Intervention Type
Drug
Intervention Name(s)
Azathioprine
Other Intervention Name(s)
Imurel (Azathioprine)
Intervention Description
Azathioprine: 2.5 mg/kg of weight/day. 3 months.
Intervention Type
Drug
Intervention Name(s)
Adalimumab
Other Intervention Name(s)
Humira (Adalimumab)
Intervention Description
Adalimumab 160 mg then 80 mg. After 2 wk: 40 mg as maintenance.
Primary Outcome Measure Information:
Title
Number of endoscopic recurrences
Description
Evaluation of the effectiveness on prevention of endoscopic recurrence evaluated as changes in the Rutgeerts Index.
Time Frame
52 weeks after the begin of the study
Secondary Outcome Measure Information:
Title
Number of Crohns´disease remission
Description
% of patients showing clinical remission after 24 and 52 weeks of adalimumab vs azathioprin treatment
Time Frame
24 weeks
Title
Number of postsurgical recurrences
Description
Evaluation of the Adalimumab efficiency on preventing postsurgical recurrence with Magnetic Resonance Enterography
Time Frame
52 week
Title
number of hospitalized patients
Description
Comparing hospitalization percentage in patients using adalimumab or azathioprin after 52 weeks of treatment
Time Frame
52 weeks
Title
Concentration of activity markers
Description
Evaluating changes in markers such as reactive c-protein, variable surface glycoprotein , faecal calprotectin, etc.
Time Frame
24 weeks
Title
Number of surgeries
Description
Comparing % of patients who needs surgery on Adalimumab vs Azatioprine
Time Frame
Until 52 week
Title
SIBDQ and EuroQOL indexes
Description
Quality of life
Time Frame
24 Weeks
Title
Number of Adverse event reports
Description
Comparison of safety of Adalimumab versus Azatioprine.
Time Frame
52 weeks
Title
Number of Crohns´disease remission
Description
% of patients showing clinical remission after 24 and 52 weeks of adalimumab vs azatioprine treatment
Time Frame
52 weeks
Title
Concentration of activity markers
Description
Evaluating changes in markers such as reactive c-protein, VSG, faecal calprotectine, etc
Time Frame
52 weeks
Title
SIBDQ and EuroQOL indexes
Description
Quality of life
Time Frame
52 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pilar Nos, MD
Organizational Affiliation
Hospital Universitari i Politecnic La Fe (Valencia, Spain)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Germans Trias i Pujol
City
Badalona
State/Province
Barcelona
Country
Spain
Facility Name
Hospital Parc Tauli
City
Sabadell
State/Province
Barcelona
Country
Spain
Facility Name
Hospital Mutua de Terrasa
City
Terrasa
State/Province
Barcelona
Country
Spain
Facility Name
Hospital Puerto Real
City
Puerto Real
State/Province
Cádiz
Country
Spain
Facility Name
Hospital General Dr. Negrín
City
Las Palmas de Gran Canaria
State/Province
Islas Canarias
Country
Spain
Facility Name
Hospital Arquitecto Marcide
City
Ferrol
State/Province
La Coruña
Country
Spain
Facility Name
Hospital de Fuenlabrada
City
Fuenlabrada
State/Province
Madrid
Country
Spain
Facility Name
Hospital de Manises
City
Manises
State/Province
Valencia
Country
Spain
Facility Name
Hospital de Bellvitge
City
Barcelona
Country
Spain
Facility Name
Hospital del Mar
City
Barcelona
Country
Spain
Facility Name
Hospital Reina Sofía
City
Córdoba
Country
Spain
Facility Name
Hospital Clínico San Carlos
City
Madrid
Country
Spain
Facility Name
Hospital Doce de Octubre
City
Madrid
Country
Spain
Facility Name
Hospital Gregorio Marañón
City
Madrid
Country
Spain
Facility Name
Hospital La Paz
City
Madrid
Country
Spain
Facility Name
Hospital La Princesa
City
Madrid
Country
Spain
Facility Name
Hospital Puerta de Hierro
City
Madrid
Country
Spain
Facility Name
Hospital Ramón y Cajal
City
Madrid
Country
Spain
Facility Name
Hospital Virgen de la Macarena
City
Sevilla
Country
Spain
Facility Name
Hospital Universitari i Policlinic La Fe
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Hospital Clínico
City
Valencia
Country
Spain
Facility Name
Hospital Río Hortega
City
Valladolid
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
28402454
Citation
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.
Results Reference
derived

Learn more about this trial

Adalimumab on Preventing Post-chirurgic Recurrence on Crohn´s Disease

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