Thalidomide Versus Infliximab in New Onset Crohn's Disease With Poor Prognostic Factors
- Registration Number
- NCT03221166
- Lead Sponsor
- IRCCS Burlo Garofolo
- Brief Summary
Crohn's disease (CD) is a life-long inflammatory bowel disease disease with an unknown pathogenesis. The ultimate goal of therapy is to modify the natural history of CD thus reducing complications. Thalidomide is a small molecule with immunomodulatory and anti-angiogenetic properties. It is currently approved for the treatment of erythema nodosum leprosum, an immunological complication of leprosy and multiple myeloma. It has also been used in several other inflammatory diseases of the skin and of the mucosal membranes, such as Behcet disease, oropharyngeal ulcers in AIDS, cutaneous lupus, and graft versus host disease. Many case series and one pediatric randomized controlled trial proved the efficacy of thalidomide in the treatment of children with CD refractory to standard treatments. In these patients, clinical remission was achieved in about 50% of the cases and was maintained for a mean time superior of 3 years. Mucosal healing after 52 weeks of treatment was observed in 40% of the patients in clinical remission. Moreover, thalidomide was found to have a steroid-sparing effect and to decrease the need for surgical interventions. The clinical and endoscopic efficacy of thalidomide was also observed in children with failure to respond or intolerance to anti-TNF biological drugs.
The aim of this multicentric prospective randomized controlled is to evaluate the efficacy and safety of thalidomide vs infliximab in changing the natural history of CD in patients with poor prognostic outcome. Moreover, the study will evaluate the immunological and genetical mechanisms of CD, the mechanisms of action thalidomide in CD and will the pharmacokinetics, metabolomics and pharmacogenomics of thalidomide, and their impact on thalidomide safety and effectiveness.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 9
-
Age at diagnosis <18 years and >=6 years
-
New diagnosis of CD based on Porto criteria
-
CD with inflammatory phenotype (non-penetrating, non-fistulizing) and with no need for surgery except for perinal fistulas
-
Presence of at least one of the following risk factors for poor prognosis:
- fistulizing perianal disease
- pan-enteric disease
- disease extension > 60 cm
- severe growth delay (height z-score < -2 DS)
- severe osteoporosis (z score < -2 DS)
- hypoalbuminemia (< 3g/dL) or high C-reactive protein (2 times higher the normal range)
-
Acceptance of the Risk Evaluation and Mitigation Strategy (REMS) program for reducing the teratogenic risk.
- ongoing pregnancy
- presence of peripheral neuropathy
- HIV
- patients with transplanted organs
- ongoing major infections or other severe diseases
- participation to other experimental studies.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Thalidomide Thalidomide Thalidomide is a immunomodulatory and antiangiogenetic drug with anti tumor necrosis factor (TNF) alpha properties Infliximab Infliximab Infliximab is a chimeric monoclonal antibody against TNF alpha
- Primary Outcome Measures
Name Time Method Efficacy in inducing mucosal healing 52 weeks Proportion of patients that achieve mucosal healing, defined by a Simplified Endoscopic Activity Index for CD (SES-CD) ≤ 2.
- Secondary Outcome Measures
Name Time Method Efficacy in inducing clinical remission 52 weeks Clinical remission will be evaluated with the weighted Pediatric Crohn's Disease Activity Index (wPCDAI), defined by a wPCDAI \<12.5.
Efficacy in reducing the need to change therapy 52 weeks Evaluation of the proportion of patients that need a therapeutic change
Efficacy in reducing hospitalizations 52 weeks Evaluation of the proportion of patients that need hospitalization.
Efficacy in inducing clinical response 52 weeks Clinical response will be evaluated with the weighted Pediatric Crohn's Disease Activity Index (wPCDAI), defined by a reduction of wPCDAI \> 50% from the basal values.
Efficacy in reducing the need for surgery 52 weeks Evaluation of the proportion of patients that need surgery
Efficacy in reducing erythrocyte sedimentation rate Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks) Evaluation of the trend of erythrocyte sedimentation rate (ESR)
Efficacy in reducing C-reactive protein Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks) Evaluation of the trend of C-reactive protein (CRP)
Efficacy in reducing faecal calprotectin Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks) Evaluation of the trend of faecal calprotectin
Efficacy in modifying body mass index Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks) Evaluation of the trend of body mass index, defined as weight (kg)/height (m)\^2
Efficacy in modifying height-for-age z score Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks) Evaluation of the trend of height-for-age z score
Efficacy in modifying weight-for-age z score Each time point between enrolment and 52 weeks (0, 4, 8, 14, 26, 38, 52 weeks) Evaluation of the trend of weight-for-age z score
Evaluation of the Treatment-Emergent Adverse Events Between enrolment and 52 weeks Number and type
Direct and indirect costs 52 weeks Comparison of direct and indirect costs (i.e. drugs, medical supplies and equipment, laboratory and diagnostic tests, hospitalizations, visits, transportation to and from healthcare facilities, missing work and school days...) between the two groups
Trial Locations
- Locations (6)
Gastroenterologia e Nutrizione Pediatrica, Azienda Ospedaliero Universitaria Meyer
🇮🇹Firenze, Toscana, Italy
IRCCS Burlo Garofolo
🇮🇹Trieste, Friuli Venezia Giulia, Italy
Fondazione MBBM , Azienda Ospedaliera San Gerardo - Università Milano Bicocca
🇮🇹Monza, Lombardia, Italy
Pediatria III Gastroenterologia ed Endoscopia Digestiva, Istituto Giannina Gaslini
🇮🇹Genoa, Liguria, Italy
Dipartimento di Pediatria dell'Università di Napoli "Federico II"
🇮🇹Napoli, Campania, Italy
Unità di Gastroenterologia Pediatrica e Fibrosi Cistica, Dipartimento di Scienze Pediatriche Mediche e Chirurgiche, Policlinico Universitario
🇮🇹Messina, Sicilia, Italy