A Randomized Study of IVIG vs. IVIG With High Dose Methylprednisolone in Childhood ITP.
Condition: Immune Thrombocytopenic Purpura
MeSH terms: Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic
Study type: Interventional
Phase: Phase 3

Summary: 
      Childhood immune thrombocytopenia purpura (ITP) is a disorder characterized by the production
      of antibodies against platelets, resulting in enhanced destruction of platelets. Most
      children with ITP present with low platelet counts (PC) but minimal bleeding. Very rarely a
      child may present with a severe life-threatening bleed, such as a bleed in the head. In this
      case it is very important that the PC be raised as quickly as possible. The combination of
      corticosteroids and intravenous gammaglobulin (IVIG) is commonly used in the management of
      such severe bleeding in children with ITP to quickly raise the PC and yet this treatment
      combination has not been tested against using IVIG alone. If it is shown that the combination
      of these agents does result in a quicker rise in PC then when using IVIG alone would support
      the use of this combination therapy in emergency situations.

      As we can not ethically conduct this study in patients with life-threatening bleeds, we plan
      to study patients with ITP and PC less than 20 X 109/L, but without life threatening
      bleeding. Eligible patients will be randomized to one of these 2 regimens (IVIG + placebo or
      IVIG + IV corticosteroids). The study is designed as a double-blind trial, where the patient
      or the treating physician will not be aware of the regimen that a patient is randomized to.
      PC's will be measured as a surrogate measure of bleeding risk; bleeding scores (a score
      generated by observing patients for bleeding symptoms) will be used to grade bleeding
      severity, and adverse effects to treatment will be monitored by the means of questionnaires
      throughout the study.
    

Detailed description: 
      Rarely children with immune thrombocytopenia purpura (ITP) can present with severe or
      life-threatening bleeding. In these cases it is very important that the platelet count be
      raised as quickly as possible. Several studies have shown that IVIG and corticosteroids on
      their own can raise platelet counts, but few studies have examined how the combination of
      IVIG and corticosteroids compares to IVIG alone in raising platelet counts in childhood ITP.
      Yet despite the lack of conclusive evidence to indicate that steroids given together with
      IVIG is more effective, this combination treatment is often given when children present with
      a life-threatening bleed, e.g. intracranial bleed. In addition to presumed greater
      effectiveness of giving the two agents together there is also evidence to show that the
      combination of IVIG with steroids may have other beneficial effects, in addition to greater
      effectiveness at raising platelet counts. This can include reducing side effects of IVIG.

      We propose to compare the effectiveness of the combination of IVIG with corticosteroids to
      IVIG alone in raising platelet counts in children with ITP and a platelet count less than 20
      x 109/L. Patient will be eligible only if they in conjunction with their treating physician
      have decided to be treated with IVIG. In this way they will require an intravenous regardless
      of study participation. The primary outcome is the rise in platelet count as reflected by the
      platelet count at 24 hours.

      Hypothesis:

      IVMP and IVIG, administered together, will

        1. increase the PC faster, and

        2. minimize the adverse effects of IVIG, and

        3. lead to a more sustained increase in PC (longer time before needing retreatment) If it
           is shown that the combination of these agents does result in a quicker rise in PC, this
           would support and justify the use of the combination therapy in emergency situations.

      Study Proposal and Methods:

      We propose to prospectively evaluate 2 treatment regimens in patients with childhood ITP:

      Regimen A: Placebo followed by IVIG 1 g/kg (Gamunex® Immune Globulin Intravenous [Human],
      10%; Bayer)* x 1 dose Regimen B: Combination therapy (IV MP (Solu-Medrol®, Upjohn) 30 mg/kg
      (max. 1 g) over 30 min followed by IVIG 1 g/kg (Gamunex® Immune Globulin Intravenous [Human],
      10%; Bayer)* x 1 dose

      *Gamunex will be given according to manufacturer's guidelines. Gamunex has been demonstrated
      to be safely and effectively administered by means of a rapid infusion protocol whereby it
      can be given over a period of 2 hours (although in some cases it needs to be given at a
      slower rate over a longer period of time).
    

Intervention name(s): Methylprednisolone and IVIG; Placebo and IVIG
Intervention type(s): Drug; Drug
Intervention description(s): Combination therapy (IV MP (Solu-Medrol®, Upjohn) 30 mg/kg (max. 1 g) over 1 hour followed by IVIG 1 g/kg (Gamunex Immune Globulin Intravenous [Human], 10%; Bayer)* x 1 dose; Placebo followed by IVIG 1 g/kg (Gamunex Immune Globulin Intravenous [Human], 10%; Bayer)* x 1 dose
Other intervention name(s): Solumedrol
Intervention MeSH terms: Methylprednisolone; Methylprednisolone Hemisuccinate; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Thrombocytopenia; pediatric; methylprednisolone; intracranial hemorrhage; intravenous immune globulin