Isoagglutinins in the Development of IVIG-associated Hemolysis

Elucidation of the Mechanism of IVIG-Associated Hemolysis

Sponsors

Lead Sponsor: Toronto Transfusion Medicine Collaborative

Collaborator: University Health Network, Toronto
Sunnybrook Health Sciences Centre
Mount Sinai Hospital, New York
The Hospital for Sick Children
St. Michael's Hospital, Toronto
Women's College Hospital

Source Toronto Transfusion Medicine Collaborative
Brief Summary

Patients at high risk of IVIG-associated hemolysis (defined as receipt of a 28-day cumulative dose of ≥ 2 g/kg, adjusted for ideal body weight, and non-O blood group) will be prospectively monitored using a standardized protocol for signs of hemolysis, and will be undergo additional testing for variables that have been hypothesized to increase the risk of hemolysis. The goal of the study is to define the incidence and dynamics of IVIG-mediated hemolysis and identify patient and product-related factors that may predict which patients are especially at risk.

Detailed Description

All IVIG orders received by the blood transfusion service at participating sites will be screened for patient eligibility. All non-O blood group patients receiving a cumulative 28-day dose of IVIG ≥ 2 g/kg will be approached for enrolment. Exclusion criteria include the presence of an alternate cause of anemia, including blood loss, other drug-induced hemolysis, anemia associated with chemotherapy for cancer, or hemolysis associated with an underlying disease or participation in another ongoing study. Patients receiving repeated courses of therapy will be eligible for re-enrollment a maximum of 6 times. There are otherwise no exclusions on the basis of age, diagnosis, concurrent treatment, or specific brand of product received. Enrolment will occur at multiple Canadian health care facilities.

Upon enrolment,case report forms documenting the participant's previous medical history, IVIG treatments and adverse reactions, and concurrent medication use will be collected. Laboratory testing for hemolysis will be performed at baseline, immediately following the completed high-dose cycle (usually administered over 1-2 days), and then again at 5-10 days post-infusion. IVIG associated. Hemolysis will be defined and graded as per the criteria of the Canadian IVIG Pharmacovigilance Group. The pathophysiology of IVIG-associated hemolysis will be characterized by tracking changes in serum complement levels, performing extended cytokine profiling, and conducting mononuclear phagocyte activity assays using patient monocytes. Secretor gene status, ABO zygosity and FcR polymorphisms will also be determined. A predictive model incorporating both patient factors (eg., blood group, total dose prescribed, presence of pre-infusion inflammation) and product factors (eg., specific lot number) will then be developed.

Overall Status Completed
Start Date October 2014
Completion Date December 2016
Primary Completion Date October 2016
Study Type Observational
Primary Outcome
Measure Time Frame
Hemolysis From initiation of IVIG therapy to 5-10 days after the completion of last IVIG infusion
Secondary Outcome
Measure Time Frame
Adverse transfusion reaction From initiation of IVIG therapy to 5-10 days after the completion of last IVIG infusion
Descriptive analysis of risk factors From initiation of IVIG therapy to 5-10 days after the completion of last IVIG infusion
Enrollment 144
Condition
Eligibility

Sampling Method: Non-Probability Sample

Criteria:

Inclusion Criteria:

- cumulative dose within a 28-day period equal or greater to 2 g/kg body weight, adjusted for lean body mass

- non-O blood group

- willing to provide blood samples immediately prior to, immediately after the completion of, and 5-10 days after the course of IVIG therapy

- Able to provide informed consent, either themselves or through a surrogate decision-maker

Exclusion Criteria:

- evidence of active bleeding or hemolytic anemia at time of enrolment (patients with chronic, stable anemia will be eligible following review by the principle investigator)

- concurrently prescribed transfusion therapy

Gender: All

Minimum Age: 3 Months

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Don Branch, PhD Principal Investigator Canadian Blood Services
Location
Facility:
Sunnybrook Health Sciences Centre | Toronto, Ontario, M4N 3M5, Canada
St. Michael's Hospital | Toronto, Ontario, M5B 1W8, Canada
The Hospital for Sick Children | Toronto, Ontario, M5G 1X8, Canada
Mount Sinai Hospital | Toronto, Ontario, M5G 2C4, Canada
University Health Network | Toronto, Ontario, M5G 2C4, Canada
Women's College Hospital | Toronto, Ontario, Canada
Location Countries

Canada

Verification Date

March 2017

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Toronto Transfusion Medicine Collaborative

Investigator Full Name: Jacob Pendergrast

Investigator Title: Consultant in Transfusion Medicine

Keywords
Has Expanded Access No
Condition Browse
Patient Data Yes
Study Design Info

Observational Model: Case-Control

Time Perspective: Prospective

Source: ClinicalTrials.gov