Preventing Intravenous Immunoglobulin-associated Adverse Reactions

Study Overview
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Brief Summary
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In patients treated with the monoclonal antibody infliximab (Remicade®) -which binds to and blocks tumor necrosis factor alpha (TNF-alpha) - an infusomat filter is routinely used to prevent the very same early adverse events observed in individuals receiving intravenous immunoglobulins (IVIG). We recently used such a filter in a patient suffering from malaise and vomiting in the context of an IVIG substitution therapy. In this patient symptoms improved and IVIG-induced complement-activation was reduced (unpublished observation). Based on this simple observation we hypothesize that this simple and approved filter-system may be efficient in retaining complement-activating immunoglobulin G (IgG) aggregates in IVIG-preparations. This effect may reduce complement activation - and consecutive inflammation - thereby diminishing adverse events. In this prospective study we propose to investigate how complement activation and side effects after IVIG infusion relate in individuals receiving conventional (i.e. unfiltered) vs. filtered IVIG-preparations.

Detailed Description
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Prospective single center study with an observational phase (phase A) and a randomized intervention-phase (phase B), monitoring adverse events and complement activation after IVIG infusion. Patients would be enrolled at the Out-patient Clinic of the Division of Hematology at the Department of Internal Medicine at the University Hospital Basel (USB). Based on the number of patients receiving IVIG at the Division of Hematology of the USB we expect to be able to complete data accrual within 8-10 months. Inclusion criteria: all patients at the Division of Hematology at the University Hospital of Basel, Switzerland after allogeneic stem cell transplant and older than 18 years which are planed for at least 2 applications of IVIG. The patients are included in this study only by informed consent. Methods: Side effects of IVIG will be monitored by use of a standardized questionnaire distributed to the nursing staff and the patients (please see attachment). Complement activation will be monitored before and after the IVIG-infusion using standard C3, C4 and 50% complement hemolytic activity (CH50) assays. Serum levels of immunoglobulin A, immunoglobulin M and immunoglobulin G will be quantified before and after IVIG-infusion. In phase A of the study we aim at including approximately 40 patients (which would be predicted to include approximately 20 patients with clinical symptoms). In phase B we would randomize these same patients into two groups of similar sizes, the first group receiving standard unfiltered IVIG infusions, the second group receiving 0.2um filtered IVIG infusions

Official Title
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Prospective Assessment of 0.2 um Pore-sized Filters in Preventing Intravenous Immunoglobulin-associated Adverse Reactions

Conditions
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Immunoglobulin Therapy

Intervention / Treatment
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* Device: Infusomat filter (Codan Duofilter-Set V86-P)
* Device: IVIG application without filter (Placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients at the Division of Hematology at the University Hospital of Basel, Switzerland after allogeneic stem cell transplant and older than 18 years which are planned for at least 2 applications of IVIG. The patients are included in this study only by informed consent. Exclusion criteria: if inclusion criteria not applicable

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group I<br>IVIG infusion with filter | Device: Infusomat filter (Codan Duofilter-Set V86-P)<br>* An approved filter system may be efficient in retaining complement activating IgG aggregates in IVIG preparations. This effect may reduce complement activation and consecutive inflammation thereby diminishing adverse events during application of intravenous immunoglobulins.<br>* Other names: Codan Duofilter-Set V86-P (Ref. 43.4459);|
| Placebo Comparator: Group II<br>IVIG infusion without filter | Device: IVIG application without filter (Placebo)<br>* Application Intravenous immunoglobulins without filter (Placebo)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure activity of complement prior to and after completion of IVIG infusion with/without filter (intervention group/placebo group) in these same patients |  | Prior to and after completion of IVIG infusion with/without filter | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Monitor adverse reactions experienced by patients receiving IVIG by use of a standardized questionary |  | During IVIG infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intravenous immunoglobulin, IVIG, adverse reactions