Clinical trial NCT00675805: Preventing Intravenous Immunoglobulin-associated Adverse Reactions
Official title: Prospective Assessment of 0.2 um Pore-sized Filters in Preventing Intravenous Immunoglobulin-associated Adverse Reactions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Immunoglobulin Therapy
Keywords: intravenous immunoglobulin
IVIG
adverse reactions
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2008-05-12
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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 In this patient symptoms improved and IVIG-induced complement-activation was reduced (unpublished observation).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: 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

Eligibility criteria: 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

Primary outcomes:
measure: Measure activity of complement prior to and after completion of IVIG infusion with/without filter (intervention group/placebo group) in these same patients
timeFrame: Prior to and after completion of IVIG infusion with/without filter
Secondary outcomes:
measure: Monitor adverse reactions experienced by patients receiving IVIG by use of a standardized questionary
timeFrame: During IVIG infusion
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel, Switzerland
state: Canton Basel-Town
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Christoph Hess, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Katz U, Achiron A, Sherer Y, Shoenfeld Y. Safety of intravenous immunoglobulin (IVIG) therapy. Autoimmun Rev. 2007 Mar;6(4):257-9. doi: 10.1016/j.autrev.2006.08.011. Epub 2006 Aug 28.
citation: Jarius S, Eichhorn P, Albert MH, Wagenpfeil S, Wick M, Belohradsky BH, Hohlfeld R, Jenne DE, Voltz R. Intravenous immunoglobulins contain naturally occurring antibodies that mimic antineutrophil cytoplasmic antibodies and activate neutrophils in a TNFalpha-dependent and Fc-receptor-independent way. Blood. 2007 May 15;109(10):4376-82. doi: 10.1182/blood-2005-12-019604. Epub 2007 Jan 30.