Eltrombopag & Cyclosporine in Children With Sever Aplastic Anemia
Condition: Eltrombopag
MeSH terms: Anemia, Aplastic
Study type: Interventional
Phase: Phase 4

Summary: 
      Aplastic anemia is a rare disorder characterized by pancytopenia and a hypo cellular bone
      marrow.but,It is very serious disease causing morbidity and mortality.

      Aplastic anemia can be treated effectively with haematopoietic stem cell transplantation and
      immunosuppressive drug regimens but haematopoietic stem cell transplantation has limitations
      due to its cost and many patient are unsuitable. Immunosuppressive drug has a significant
      number of patients have persistent cytopenias. Currently, the treatment of these patients is
      regular transfusion, which are expensive, inconvenient, and associated with serious side
      effects related to iron overload and transfusion.

      Eltrombopag is an oral thrombopoietin mimetic that selectively binds at the transmembrane and
      juxtamembrane domains of the thrombopoietin receptor, at sites distinct from the binding site
      of thrombopoietin therefore it does not compete for binding with the native molecule. It
      promoting thrombopoiesis and release of platelets from mature megakaryocytes. Also, promote
      other hematopoietic stem cell as well as in thrombopoiesis .
    

Detailed description: 
      Aplastic anemia is a rare disorder characterized by pancytopenia and a hypo cellular bone
      marrow.This causes a deficiency of all three blood cell types (pancytopenia): red blood cells
      (anemia), white blood cells (leukopenia), and platelets (thrombocytopenia) . The clinical
      consequences are anemia, usually with a requirement for frequent red blood cell transfusions,
      life-threatening bleeding from thrombocytopenia, and infection because of neutropenia.
      Bacterial and fungal infections are most common and are a significant cause of morbidity and
      mortality.

      The incidence of acquired Aplastic anemia in Europe and North America is around two per
      million children per year . The incidence is 2-3 times higher in East Asia. There is no
      significant difference in incidence between males and females .

      The pathogenesis of Aplastic anemia is complex and involves an abnormal hematopoietic
      microenvironment, hematopoietic stem cell/progenitor cell deficiencies and immunity
      disorders. The etiological basis for marrow failure includes primary defects in or damage to
      the stem cell or the marrow microenvironment. The distinction between acquired and inherited
      disease may present a clinical challenge, Congenital or inherited causes of Aplastic anemia
      are responsible for at least 25% of children with this condition and for perhaps up to 10% of
      adults. Acquired causes of Aplastic anemia form (80%) of cases, include Idiopathic (> 80 %),
      Post-infectious 15% (particularly after hepatitis 9%, Epstein-Barr virus , human immune
      deficiency virus, parvovirus, and mycobacteria, Drug-induced and toxins (4%).

      Definitive and potentially curative therapy with haematopoietic stem cell transplantation
      However, only a minority (30 %) of patients have a suitable donor. Immunosuppressive therapy
      with horse or rabbit antithymocyte globulin plus cyclosporine is the most commonly used
      alternative treatment in about two thirds of cases. Response is associated with a favorable
      long-term outlook. 30 -40% of patients are refractory to immunosuppressive therapy and remain
      pancytopenic after therapy. Even patients that respond to immunosuppressive therapies with an
      improvement in their life-threatening neutropenia sometimes have persistent thrombocytopenia
      .

      Aplastic anemia can be treated effectively with haematopoietic stem cell transplantation and
      immunosuppressive drug regimens but haematopoietic stem cell transplantation has limitations
      due to its cost and many patient are unsuitable. Immunosuppressive drug has a significant
      number of patients have persistent cytopenias. Currently, the treatment of these patients is
      regular transfusion, which are expensive, inconvenient, and associated with serious side
      effects related to iron overload and transfusion.

      Thrombopoietin is a glycoprotein class 1 hematopoietic cytokine, produced primarily in the
      liver. It is a critical regulator of hematopoiesis. It acts through the thrombopoietin
      receptor which is expressed on hematopoietic stem and progenitor cells. Action results in a
      number of signal transduction events that prevent apoptosis, improve cell viability, promote
      growth, and possibly increase differentiation.

      Eltrombopag is an oral thrombopoietin mimetic that selectively binds at the transmembrane and
      juxtamembrane domains of the thrombopoietin receptor, at sites distinct from the binding site
      of thrombopoietin therefore it does not compete for binding with the native molecule. It
      promoting thrombopoiesis and release of platelets from mature megakaryocytes. Also, promote
      other hematopoietic stem cell as well as in thrombopoiesis .Eltrombopag became the first oral
      platelet growth factor to receive Food and Drug Administration approval in 2008. This initial
      indication was for adult patients with chronic immune thrombocytopenic purpura. In 24 August
      2015, this indication was extended to children age 1 to 17 with the same condition. In
      addition, it has been recently shown to be efficacious in the setting of aplastic anemia with
      trilineage responses in some patients and many achieving transfusion independence. It has
      license by the European Medicines Agency for this indication in August 2015. In 2017, the
      National Institutes of Health made Eltrombopag a standard of care in Aplastic anemia
    

Intervention name(s): Eltrombopag
Intervention type(s): Drug
Intervention description(s): An oral thrombopoietin receptor agonist
Other intervention name(s): Revolade
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment