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

NCT01564823 | Completed Phase 3

• 1 other identifier: APPRECIA
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 22

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.

Conditions

Crohn´s Disease

Keywords

Crohn´s disease; Metronidazole; Azathioprine; Adalimumab; post-chirurgic recurrence

Outcome Measures

Primary Outcomes (1)

• Number of endoscopic recurrences

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

  52 weeks after the begin of the study

Secondary Outcomes (10)

• Number of Crohns´disease remission

  24 weeks

• Number of postsurgical recurrences

  52 week

• number of hospitalized patients

  52 weeks

• Concentration of activity markers

  24 weeks

• Number of surgeries

  Until 52 week

Study Arms (2)

Metronidazole + Azathioprine.

EXPERIMENTAL

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

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.

Drug: Metronidazole; Drug: Adalimumab

Interventions

Metronidazole DRUG

Metronidazole: 250 mg/8h. 3 months.

Also known as: Flagyl (Metronidazole)

Metronidazole + Azathioprine.

Azathioprine DRUG

Azathioprine: 2.5 mg/kg of weight/day. 3 months.

Also known as: Imurel (Azathioprine)

Metronidazole + Azathioprine.

Adalimumab DRUG

Adalimumab 160 mg then 80 mg. After 2 wk: 40 mg as maintenance.

Also known as: Humira (Adalimumab)

Metronidazole + Adalimumab

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 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa: lead
• Effice Servicios Para la Investigacion S.L.: collaborator

Study Sites (22)

Hospital Germans Trias i Pujol

Badalona, Barcelona, Spain

Location

Hospital de Bellvitge

Barcelona, Barcelona, Spain

Location

Hospital del Mar

Barcelona, Barcelona, Spain

Location

Hospital Parc Tauli

Sabadell, Barcelona, Spain

Location

Hospital Mutua de Terrasa

Terrassa, Barcelona, Spain

Location

Hospital General Dr. Negrín

Las Palmas de Gran Canaria, Canary Islands, Spain

Location

Hospital Puerto Real

Puerto Real, Cádiz, Spain

Location

Hospital Reina Sofía

Córdoba, Córdoba, Spain

Location

Hospital Arquitecto Marcide

Ferrol, La Coruña, Spain

Location

Hospital de Fuenlabrada

Fuenlabrada, Madrid, Spain

Location

Hospital Clínico San Carlos

Madrid, Madrid, Spain

Location

Hospital Doce de Octubre

Madrid, Madrid, Spain

Location

Hospital Gregorio Marañón

Madrid, Madrid, Spain

Location

Hospital La Paz

Madrid, Madrid, Spain

Location

Hospital La Princesa

Madrid, Madrid, Spain

Location

Hospital Puerta de Hierro

Madrid, Madrid, Spain

Location

Hospital Ramón y Cajal

Madrid, Madrid, Spain

Location

Hospital Virgen de la Macarena

Seville, Sevilla, Spain

Location

Hospital de Manises

Manises, Valencia, Spain

Location

Hospital Universitari i Policlinic La Fe

Valencia, Valencia, 46026, Spain

Location

Hospital Clínico

Valencia, Valencia, Spain

Location

Hospital Río Hortega

Valladolid, Valladolid, Spain

Location

Related Publications (1)

• 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.

  PMID: 28402454 DERIVED

MeSH Terms

Conditions

Crohn Disease

Interventions

Metronidazole; Azathioprine; Adalimumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thionucleosides; Sulfur Compounds; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Pilar Nos, MD

  Hospital Universitari i Politecnic La Fe (Valencia, Spain)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2012
• First Posted: March 28, 2012
• Study Start: June 1, 2012
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: March 17, 2015

Record last verified: 2015-03

Locations

ES (22)