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A Randomized Study of IVIG vs. IVIG With High Dose Methylprednisolone in Childhood ITP.

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by The Hospital for Sick Children
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Manuel Carcao, The Hospital for Sick Children
ClinicalTrials.gov Identifier:
NCT00376077
First received: September 12, 2006
Last updated: November 19, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Immune Thrombocytopenic Purpura
Drug: Methylprednisolone and IVIG
Drug: Placebo and IVIG
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized Study of IVIG vs. IVIG With High Dose Methylprednisolone in Rapidly Augmenting Platelet Counts in Childhood ITP.

Resource links provided by NLM:


Further study details as provided by The Hospital for Sick Children:

Primary Outcome Measures:
  • The rapidity of rise in Platelet Count [ Time Frame: The first 24 hours following the administration of therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Days to PC falling to < 20 x 109/L [ Time Frame: Time frame determined by outcome ] [ Designated as safety issue: No ]
  • Adverse Effects of therapy [ Time Frame: 1 week ] [ Designated as safety issue: No ]
  • Quality of life changes over time and between the treatment groups [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: August 2005
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Placebo and IVIG

The trial site is blinded to the randomization process. Patients are assigned an arm by a research pharmacist. Patients on this arm receive an infusion of placebo (0.9% NaCl) over one hour. Immediately following this dosing, 1 g/kg IVIG (Gammunex ©) is infused over 2 - 3 hours. Following this treatment, complete blood counts are drawn at:

  • completion of IVIG infusion,
  • 8 hours following the start of the placebo/solumedrol infusion
  • 24 hours following the start of the placebo/solumedrol infusion
  • 72 hours following the start of the placebo/solumedrol infusion
  • 7 days post infusion
  • 21 days post infusion
Drug: Placebo and IVIG
Placebo followed by IVIG 1 g/kg (Gamunex Immune Globulin Intravenous [Human], 10%; Bayer)* x 1 dose
Experimental: Methylprednisolone and IVIG

The trial site is blinded to the randomization process. Patients are assigned an arm by a research pharmacist.Patients on this arm receive IV Methylprednisolone 30 mg/kg (1 gram maximum) infused over one hour. Immediately following this dosing, 1 g/kg IVIG Gammunex © is infused over 2 - 3 hours. Following this treatment, complete blood counts are drawn at:

  • completion of IVIG infusion,
  • 8 hours following the start of the placebo/solumedrol infusion
  • 24 hours following the start of the placebo/solumedrol infusion
  • 72 hours following the start of the placebo/solumedrol infusion
  • 7 days post infusion
  • 21 days post infusion
Drug: Methylprednisolone and IVIG
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
Other Name: Solumedrol

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).

  Eligibility

Ages Eligible for Study:   1 Year to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ages 1-17 yr. followed at participating centers
  • diagnosed with primary ITP
  • present with a PC < 20 x 10^9/L
  • patient and attending physician have decided on treatment of ITP

Exclusion Criteria:

  • initial presentation with ITP
  • splenectomy
  • life-threatening hemorrhage e.g. proven or suspected intracranial hemorrhage (ICH), major gastrointestinal hemorrhage with cardiorespiratory decompensation
  • organ-threatening hemorrhage e.g. hemorrhage into the eye
  • contraindication to IVIG ( renal disease with creatinine > x 2 upper list of normal )
  • contraindication of IV methylprednisolone ( diabetes mellitus, hypertension, peptic ulceration )
  • prior failure to attain a PC level over 50 X 109 within 2 weeks of treatment with IVIG of 0.8 to 1 g/kg or IV methyl-prednisolone (max 1 gram ) within 6 months prior to study entry
  • co-existing situations that could affect platelet response to therapy e.g. sepsis, fever > 38.5°C ( orally or equivalent), splenomegaly (spleen tip > 2 cm below costal margin), Disseminated Intravascular Coagulation (DIC) - defined by a fibrinogen level < 1.0 g/dL and elevated D-dimer levels, surgery
  • pregnancy (a mandatory urine pregnancy test will be obtained on all post-pubescent female patients). Such patients can only be eligible once the urine pregnancy test results are confirmed to be negative.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00376077

Contacts
Contact: Manuel Carcao, MD 416-813 5367 manuel.carcao@sickkids.ca
Contact: Victor Blanchette, MD 416-813 5852 victor.blanchette@sickkids.ca

Locations
Canada, Ontario
Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Manuel Carcao, MD    416-813 5367    manuel.carcao@sickkids.ca   
Contact: Victor Blanchette, MD    416 813 5852    victor.blanchette@sickkids.ca   
Principal Investigator: Manuel Carcao, MD         
Sponsors and Collaborators
The Hospital for Sick Children
Bayer
Investigators
Principal Investigator: Manuel Carcao, MD The Hospital for Sick Children
Principal Investigator: Victor Blanchette, MD The Hospital for Sick Children
  More Information

No publications provided

Responsible Party: Manuel Carcao, Staff Haematologist, The Hospital for Sick Children
ClinicalTrials.gov Identifier: NCT00376077     History of Changes
Other Study ID Numbers: 1000006180
Study First Received: September 12, 2006
Last Updated: November 19, 2014
Health Authority: Canada: Health Canada

Keywords provided by The Hospital for Sick Children:
Thrombocytopenia
pediatric
methylprednisolone
intracranial hemorrhage
intravenous immune globulin

Additional relevant MeSH terms:
Purpura, Thrombocytopenic
Purpura, Thrombocytopenic, Idiopathic
Autoimmune Diseases
Blood Coagulation Disorders
Blood Platelet Disorders
Hematologic Diseases
Hemorrhage
Hemorrhagic Disorders
Immune System Diseases
Pathologic Processes
Purpura
Signs and Symptoms
Skin Manifestations
Thrombocytopenia
Thrombotic Microangiopathies
Methylprednisolone
Methylprednisolone Hemisuccinate
Methylprednisolone acetate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids

ClinicalTrials.gov processed this record on November 20, 2014