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

NCT00376077 | Completed Phase 3 DMC

• 1 other identifier: 1000006180
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Immune Thrombocytopenic Purpura

Keywords

Thrombocytopenia; pediatric; methylprednisolone; intracranial hemorrhage; intravenous immune globulin

Outcome Measures

Primary Outcomes (1)

• The rapidity of rise in Platelet Count

  The first 24 hours following the administration of therapy

Secondary Outcomes (3)

• Days to PC falling to < 20 x 109/L

  Time frame determined by outcome

• Adverse Effects of therapy

  1 week

• Quality of life changes over time and between the treatment groups

  6 months

Study Arms (2)

Placebo and IVIG

ACTIVE COMPARATOR

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

Methylprednisolone and IVIG

EXPERIMENTAL

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

Interventions

Methylprednisolone and IVIG DRUG

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

Also known as: Solumedrol

Methylprednisolone and IVIG

Placebo and IVIG DRUG

Placebo followed by IVIG 1 g/kg (Gamunex Immune Globulin Intravenous \[Human\], 10%; Bayer)\* x 1 dose

Placebo and IVIG

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Hospital for Sick Children: lead
• Bayer: collaborator

Study Sites (1)

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Related Publications (1)

• 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.

  PMID: 32282882 DERIVED

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Intracranial Hemorrhages

Interventions

Methylprednisolone; Immunoglobulins, Intravenous; Methylprednisolone Hemisuccinate

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Manuel Carcao, MD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

• Victor Blanchette, MD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Haematologist

Study Record Dates

• First Submitted: September 12, 2006
• First Posted: September 14, 2006
• Study Start: August 1, 2005
• Primary Completion: March 1, 2016
• Study Completion: April 1, 2016
• Last Updated: May 9, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will share

Locations

CA (1)