Impatto Clinico Dell'Anemia Nelle Malattie Infiammatorie Intestinali: Ruolo Della Carenza di Ferro e Della Terapia Sostitutiva Con Ferro, Trial Terapeutico (RIDART II)

Anemia is the most common extraintestinal manifestation of inflammatory bowel diseases (IBD). Most cases of anemia in IBD are due to iron deficiency (IDA) and to anemia of inflammation (AI) (Bergamaschi et al, 2010). Guidelines by the European Crohn's and Colitis Organisation (ECCO) suggest that iron supplementation should be started when IDA is present or even in the presence of iron deficiency without anemia (Dignass et al, 2015). However, many IBD patients with IDA are not properly treate, probably due to the belief that mild to moderate degrees of anemia may not have a significant impact on the patient's quality of life, that oral iron supplementation may adversely affect disease activity, and that parenteral iron administration may cause severe side effects. In this study the investigators will compare three iron supplementation regimens (two iv iron formulations and one oral iron integrator) for the treatment of IDA in patients with IBD in terms of both efficacy and safety. Participation to the trial does not involve additional risks for the patients. In fact, the trial does not require additional diagnostic procedures beyond those that are usually performed in IBD patients and the drugs that will be use din the trial are already used in patients with IBD and IDA. According to WHO criteria (WHO scientific groupl, 1968), anemia is defined as Hb <13.0 g/dL in males and Hb <12 g/dL in females (Blanc et al, 1968). A serum ferritin <30 µg/L or a serum ferritin ≤100 µg/L with transferrin saturation <20% are required for the diagnosis of isolated IDA and of IDA associated with inflammation, respectively.

300 subjects with IDA and IBD will be recruited in a multicenter trial and randomized 1:1:1 to the three iron replacement arms. Expected duration of subject participation to the trial will be 24 weeks for each patient, consisting of an 8 week treatment period, with follow-up visits at weeks 4, 8, 12 and 24 from treatment start.

Study participants can be participating in other research, either observational or interventional, or other drug research concerning the treatment of IBD.

Iron gluconate and FCM are licensed for use in Italy and will be used according to AIC. Iron gluconate will be part of the normal hospital stock. FCM will be purchased through an IG-IBD donation to the Fondazione IRCCS Policlinico San Matteo. Microsomial iron is a formulation for oral administration commercially available in Italy as an iron integrator; for the study, however, it will be provided free of charge from Pharmanutra S.r.l.

Concomitant therapy No other iron supplementation is allowed during the trial. Vitamin integrators containing folic acid, vitamin B12 and vitamin D or calcium are allowed, as well as any other treatment for IBD and related comorbidities; therefore, study patients can be treated with topic and systemic mesalazine and steroids, or with immunosuppressors (azathioprine, mercaptopurine, cyclosporine, methotrexate) and biologic immunomodulators (infliximab, adalimumab, golimumab) commonly used in IBD patients; pain relievers and antibiotics (the latter for either infection treatment or profilaxis) can be used without restrictions.