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

Primary Purpose

Immune Thrombocytopenic Purpura

Status
Completed
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Methylprednisolone and IVIG
Placebo and IVIG
Sponsored by
The Hospital for Sick Children
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Immune Thrombocytopenic Purpura focused on measuring Thrombocytopenia, pediatric, methylprednisolone, intracranial hemorrhage, intravenous immune globulin

Eligibility Criteria

1 Year - 17 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Hospital for Sick Children

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Placebo and IVIG

Methylprednisolone and IVIG

Arm Description

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

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

Outcomes

Primary Outcome Measures

The rapidity of rise in Platelet Count

Secondary Outcome Measures

Days to PC falling to < 20 x 109/L
Adverse Effects of therapy
Quality of life changes over time and between the treatment groups

Full Information

First Posted
September 12, 2006
Last Updated
May 5, 2016
Sponsor
The Hospital for Sick Children
Collaborators
Bayer
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1. Study Identification

Unique Protocol Identification Number
NCT00376077
Brief Title
A Randomized Study of IVIG vs. IVIG With High Dose Methylprednisolone in Childhood ITP.
Official Title
A Randomized Study of IVIG vs. IVIG With High Dose Methylprednisolone in Rapidly Augmenting Platelet Counts in Childhood ITP.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
August 2005 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
April 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Hospital for Sick Children
Collaborators
Bayer

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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 increase the PC faster, and minimize the adverse effects of IVIG, and 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Immune Thrombocytopenic Purpura
Keywords
Thrombocytopenia, pediatric, methylprednisolone, intracranial hemorrhage, intravenous immune globulin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo and IVIG
Arm Type
Active Comparator
Arm Description
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
Arm Title
Methylprednisolone and IVIG
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Methylprednisolone and IVIG
Other Intervention Name(s)
Solumedrol
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo and IVIG
Intervention Description
Placebo followed by IVIG 1 g/kg (Gamunex Immune Globulin Intravenous [Human], 10%; Bayer)* x 1 dose
Primary Outcome Measure Information:
Title
The rapidity of rise in Platelet Count
Time Frame
The first 24 hours following the administration of therapy
Secondary Outcome Measure Information:
Title
Days to PC falling to < 20 x 109/L
Time Frame
Time frame determined by outcome
Title
Adverse Effects of therapy
Time Frame
1 week
Title
Quality of life changes over time and between the treatment groups
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Manuel Carcao, MD
Organizational Affiliation
The Hospital for Sick Children
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Victor Blanchette, MD
Organizational Affiliation
The Hospital for Sick Children
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Manuscript preparation
Citations:
PubMed Identifier
32282882
Citation
Carcao M, Silva M, David M, Klaassen RJ, Steele M, Price V, Wakefield C, Kim L, Stephens D, Blanchette VS. IVMP+IVIG raises platelet counts faster than IVIG alone: results of a randomized, blinded trial in childhood ITP. Blood Adv. 2020 Apr 14;4(7):1492-1500. doi: 10.1182/bloodadvances.2019001343.
Results Reference
derived

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

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