Preventing Intravenous Immunoglobulin-associated Adverse Reactions

NCT ID: NCT00675805

Last Updated: 2014-09-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-05-31
• Study Completion Date: 2012-12-31

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 In this patient symptoms improved and IVIG-induced complement-activation was reduced (unpublished observation).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

Conditions

Immunoglobulin Therapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Group I

IVIG infusion with filter

Group Type: ACTIVE_COMPARATOR

Infusomat filter (Codan Duofilter-Set V86-P)

Intervention Type: DEVICE

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.

Group II

IVIG infusion without filter

Group Type: PLACEBO_COMPARATOR

IVIG application without filter (Placebo)

Intervention Type: DEVICE

Application Intravenous immunoglobulins without filter (Placebo)

Interventions

Infusomat filter (Codan Duofilter-Set V86-P)

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.

Intervention Type: DEVICE

IVIG application without filter (Placebo)

Application Intravenous immunoglobulins without filter (Placebo)

Intervention Type: DEVICE

Other Intervention Names

Codan Duofilter-Set V86-P (Ref. 43.4459)

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christoph Hess, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Basel, Switzerland

Locations

University Hospital Basel, Switzerland

Basel, Canton Basel-Town, Switzerland

Countries

Switzerland

References

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.

Reference Type: BACKGROUND

PMID: 17317619 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17264299 (View on PubMed)

Other Identifiers

IVIG-001

Identifier Type: -

Identifier Source: org_study_id