Clinical trial NCT02259478: Isoagglutinins in the Development of IVIG-associated Hemolysis
Official title: Elucidation of the Mechanism of IVIG-Associated Hemolysis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Immunoglobulins, Intravenous
Hemolysis
Keywords: Intravenous Immunoglobulin (IVIG)
Hemolysis
Transfusion Medicine
Pharmacovigilance
Lead sponsor: Toronto Transfusion Medicine Collaborative
Sponsor class: OTHER
Collaborators: name: University Health Network, Toronto
name: Sunnybrook Health Sciences Centre
name: Mount Sinai Hospital, New York
name: The Hospital for Sick Children
name: Unity Health Toronto
name: Women's College Hospital
First posted: 2014-10-08
Enrollment: 144
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All orders for IVIG received by the UHN Blood Transfusion Service will be reviewed by the study coordinator to identify potential study participants

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.

Eligibility 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

Primary outcomes:
measure: Hemolysis
timeFrame: From initiation of IVIG therapy to 5-10 days after the completion of last IVIG infusion
Secondary outcomes:
measure: Adverse transfusion reaction
timeFrame: From initiation of IVIG therapy to 5-10 days after the completion of last IVIG infusion
measure: Descriptive analysis of risk factors
timeFrame: From initiation of IVIG therapy to 5-10 days after the completion of last IVIG infusion
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Toronto
country: Canada
facility: Women's College Hospital
state: Ontario
Study officials:
affiliation: Canadian Blood Services
name: Don Branch, PhD
role: PRINCIPAL_INVESTIGATOR
References: