NCT00882414

Ferinject® in Patient With Thrombocytosis Secondary to Inflammatory Bowel Disease (IBD)

A Multi-centre, Randomized, Controlled, Single-blinded, Phase II Study to Investigate the Safety and Efficacy of Intravenous Infusions of FERINJECT® Versus Placebo in Patients With Thrombocytosis Secondary to Iron Deficiency and Chronic Inflammatory Bowel Disease

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 26 (actual)
• Sponsor: Vifor Pharma · Industry
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

The aim of this study is to show the benefits for patients, with a high platelet count, iron deficiency and IBD, receiving intravenous iron therapy.

Detailed description

For the first time a platelet abnormality in IBD was reported in 1968, with a description of an increased platelet count in patients having an exacerbation of clinical activity 1. Since then it has been established that thrombocytosis and platelet activation are common features in IBD2. Both features are strongly connected to thromboembolic events, which are a major cause of patient morbidity and mortality 3. In vitro studies have so far shown that spontaneous platelet aggregation is present in more than 30% of IBD patients compared to none of the controls and besides independent of disease severity 4. Unfortunately the mechanisms behind the abnormal megakaryopoiesis are not completely understood. Nevertheless platelets can store and produce a large amount of inflammatory mediators and are activated by multiple proinflammatory substances. Therefore, platelets are regarded as a major target in the therapy of inflammatory bowel diseases 5. An increase in systemic cytokine levels such as IL-6 or IL-11 may contribute to enhanced platelet production. Also intestinal bleeding and iron deficiency, which are major symptoms of IBD, may have stimulatory effects on megakaryopoiesis 6. Previously, we observed a normalization of elevated platelet counts in IBD patients with iron deficiency anemia (IDA) upon treatment with intravenous iron sucrose 7. We therefore believe that iron deficiency is causatively involved in the pathogenesis of thrombocytosis in IBD and intend to investigate the effect of intravenous iron therapy on platelet levels and platelet activation markers in patients with IBD and iron deficiency. Vifor (International) Inc. has developed a new formulation of parenteral iron, FERINJECT® (5% w/v iron carboxymaltose in a solution of water for injection). Based on preclinical toxicity data and clinical experience, FERINJECT® does not cause anaphylactic reactions or liver toxicity. Based on human pharmacokinetic data, the estimated terminal half-life of FERINJECT® is 16 hours. The analysis of a FERINJECT® positron emission tomography (PET) study in six patients each receiving a single dose of 100mg iron as FERINJECT® demonstrated that, during the initial distribution phase, a major proportion of the dose was distributed to the bone marrow . Red cell utilization of iron was found to be high. After 24 days, patients with IDA showed a red cell utilization of 91% to 99%. Various studies demonstrated that FERINJECT® could be safely administered at doses of up to 1000mg, which is a significant advantage of FERINJECT® over iron sucrose. A multiple-dose phase I/II study in patients with IBD investigating the safety, efficacy, and kinetics of repeated doses of FERINJECT® has been completed. Patients who were treated at our unit (Medical University of Vienna) were also analyzed regarding the effect of VIT45 on platelet counts. Similar to our experience with iron sucrose, we observed a significant drop in thrombocytosis within 8 weeks pointing again to the direct effect of iron on regulating megakaryopoiesis in vivo8. This study tries to show the benefits for patients, with a high platelet count, iron deficiency and IBD, receiving intravenous iron therapy. As with all iron preparations, overdosing with respect to the total amount should be avoided. The maximum infused weekly dose of FERINJECT® will be 500 mg. Based on animal toxicity data and patient experience, FERINJECT® does not cause anaphylactic reactions or liver toxicity at the doses intended for use in this study. However, due to the relatively large doses of iron being administered, patients will be monitored carefully throughout the study for symptoms of iron overload. Potential benefits to the patients include a decrease of the platelet counts, besides a increase in hemoglobin levels and normalization of iron stores. Primary Objective: To evaluate the efficacy of FERINJECT® in reducing elevated platelet counts Secondary Objectives: To evaluate the effect of FERINJECT® on coagulation and platelet activation parameters To evaluate the efficacy of FERINJECT® in normalizing iron deficiency To evaluate the change of quality in life and disease activity To evaluate the safety of FERINJECT®

Conditions

• Thrombocytosis
• Iron-Deficiency Anemia

Interventions

Type	Name	Description
DRUG	FERINJECT® (Ferric carboxymaltose)	FERINJECT® will be administered i.v. into a peripheral vein in the arm. 500 mg FERINJECT® will be diluted to a total volume of 100mL in 0.9% saline for infusion and administered over 15 minutes duration.
DRUG	Placebo	Placebo will be administered i.v. into a peripheral vein in the arm. A total volume of 100mL 0.9% saline will be administered over 15 minutes duration.

Timeline

• Start date: 2006-12-01
• Primary completion: 2010-01-01
• Completion: 2010-01-01
• First posted: 2009-04-16
• Last updated: 2010-04-08

Locations

1 site across 1 country: Austria