Immune Thrombocytopenic PurpuraPhase 3NCT00376077
A Randomized Study of IVIG vs. IVIG With High Dose Methylprednisolone in Childhood ITP.
A Phase 3 study testing Methylprednisolone and IVIG in people with Immune Thrombocytopenic Purpura, run by The Hospital for Sick Children at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 17 years
- Conditions the study is for
- Immune Thrombocytopenic Purpura
- What is being tested?
- Methylprednisolone and IVIG
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteCanada
- Study dates
- Aug 2005to Apr 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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 )
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Study of IVIG vs. IVIG With High Dose Methylprednisolone in Rapidly Augmenting Platelet Counts in Childhood ITP.
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.
Read the 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).
- Conditions
- Immune Thrombocytopenic Purpura
- Being tested
- Methylprednisolone and IVIG, Placebo and IVIG
- Keywords
- Thrombocytopenia, pediatric, methylprednisolone, intracranial hemorrhage, intravenous immune globulin
- Medical subject headings
- Purpura, Thrombocytopenic, Idiopathic, Thrombocytopenia, Intracranial Hemorrhages
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylprednisolone and IVIGDrug
Also called Solumedrol
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 and IVIGDrug
Placebo followed by IVIG 1 g/kg (Gamunex Immune Globulin Intravenous [Human], 10%; Bayer)* x 1 dose
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Methylprednisolone and IVIG |
What is being measured
The primary outcome is the main question the study is designed to answer.
The rapidity of rise in Platelet Count
Measured: The first 24 hours following the administration of therapy
Secondary outcomes (3)
Days to PC falling to < 20 x 109/L
Measured: Time frame determined by outcome
Adverse Effects of therapy
Measured: 1 week
Quality of life changes over time and between the treatment groups
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2006 (estimated)
- Study startAug 2005
- Primary completionMar 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Immune Thrombocytopenic PurpuraStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Principal investigator, Manuel Carcao, The Hospital for Sick Children
- Investigators
- Manuel Carcao, MD, Principal investigator, The Hospital for Sick ChildrenVictor Blanchette, MD, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00376077
- Sponsor's protocol ID
- 1000006180
- Status last verified
- May 2016
- First submitted
- 12 Sep 2006
- Last updated
- 9 May 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Manuscript preparation
Publications
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.
PubMed 32282882
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Study of IVIG vs. IVIG With High Dose Methylprednisolone in Rapidly Augmenting Platelet Counts in Childhood ITP.
- ClinicalTrials.gov ID
- NCT00376077
- Acronym / sponsor ID
- 1000006180
- Conditions
- Immune Thrombocytopenic Purpura
- Keywords
- Thrombocytopenia, pediatric, methylprednisolone, intracranial hemorrhage, intravenous immune globulin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- Aug 2005
- Primary completion
- Mar 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 14 Sep 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo and IVIG | Active comparator | Drug: Placebo and IVIGThe 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 |
| Methylprednisolone and IVIG | Experimental | Drug: Methylprednisolone and IVIGThe 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 |
Who may qualify
- Ages
- 1 year to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (9 listed)
- 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 )
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methylprednisolone and IVIGAlso: SolumedrolCombination 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 | Drug | Methylprednisolone and IVIG |
| Placebo and IVIGPlacebo followed by IVIG 1 g/kg (Gamunex Immune Globulin Intravenous [Human], 10%; Bayer)* x 1 dose | Drug | Placebo and IVIG |
Primary outcome
The rapidity of rise in Platelet Count
Time frame: The first 24 hours following the administration of therapy
3 secondary outcomes
Days to PC falling to < 20 x 109/L
Time frame: Time frame determined by outcome
Adverse Effects of therapy
Time frame: 1 week
Quality of life changes over time and between the treatment groups
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2016.
- Derived from this study: PubMed 32282882Carcao 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.
- Individual participant dataSharing planned: Yes. Manuscript preparation
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Manuel Carcao, MD principal investigator
The Hospital for Sick Children
Victor Blanchette, MD principal investigator
The Hospital for Sick Children
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Methylprednisolone and IVIG in people with Immune Thrombocytopenic Purpura, run by The Hospital for Sick Children at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The rapidity of rise in Platelet Count (time frame: The first 24 hours following the administration of therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00376077, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2016.