Immunoglobulins, IntravenousNCT02259478
Isoagglutinins in the Development of IVIG-associated Hemolysis
An observational study of Immunoglobulins, Intravenous and Hemolysis, run by Toronto Transfusion Medicine Collaborative at 6 sites in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 3 months and older
- Conditions the study is for
- Immunoglobulins, Intravenous, Hemolysis
- How many people
- 144 participants
- Where
- 6 sitesCanada
- Study dates
- Oct 2014to Dec 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Canada6 sites
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
St. Michael's Hospital
Toronto, Ontario, M5B 1W8
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8
Mount Sinai Hospital
Toronto, Ontario, M5G 2C4
University Health Network
Toronto, Ontario, M5G 2C4
Women's College Hospital
Toronto, Ontario
About this study
Official title: Elucidation of the Mechanism of IVIG-Associated Hemolysis
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.
Read the 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.
- Conditions
- Immunoglobulins, Intravenous, Hemolysis
- Keywords
- Intravenous Immunoglobulin (IVIG), Hemolysis, Transfusion Medicine, Pharmacovigilance
- Medical subject headings
- Hemolysis
What is being measured
The primary outcome is the main question the study is designed to answer.
Hemolysis
Definition and grading of hemolysis adopted from the Canadian IVIG Hemolysis Pharmacovigilance Group
Measured: From initiation of IVIG therapy to 5-10 days after the completion of last IVIG infusion
Secondary outcomes (2)
Adverse transfusion reaction
Any patient symptom reported during or within 10 days of an IVIG infusion will be considered as a possible adverse transfusion reaction. Symptoms deemed to most likely indicate an adverse reaction include the development of fever, chills or rigours; allergic reactions (urticaria, angioedema or anaphylaxis); pain reactions (including headache); respiratory symptoms (cough, shortness of breath); and signs suggestive of anemia or hemolysis (pallor, fatigue, red-coloured urine, jaundice)
Measured: From initiation of IVIG therapy to 5-10 days after the completion of last IVIG infusion
Descriptive analysis of risk factors
Additional secondary outcomes will include a descriptive analysis of information collected on the initial case report form such as patient demographics, medical history, dose and lot of IVIG administered, infusion rate, patient blood group, and concurrent medications. In addition, patient samples will be sent for additional testing aimed at elucidating the mechanism of IVIG-mediated hemolysis. These include:
- Cytokine panel profiling
- C3, C4, ferritin and CRP levels
- Monocyte monolayer assay using patient monocytes and implicated lot of IVIG against AET-treated group A1, B, and O red cells
- Tests of eluted IgG antibody for subtype.
- ABO zygosity (PCR) and/or by Flow
- FcR polymorphisms by PCR
- Secretor status by PCR
Measured: From initiation of IVIG therapy to 5-10 days after the completion of last IVIG infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2014 (estimated)
- Study startOct 2014
- Primary completionOct 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Immunoglobulins, IntravenousStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 144 participants (actual)
Sponsor and investigators
- Lead sponsor
- Toronto Transfusion Medicine Collaborative
- Sponsor type
- University, hospital or other
- Collaborators
- University Health Network, Toronto, Sunnybrook Health Sciences Centre, Mount Sinai Hospital, New York, The Hospital for Sick Children, Unity Health Toronto, Women's College Hospital
- Responsible party
- Principal investigator, Jacob Pendergrast, Toronto Transfusion Medicine Collaborative
- Investigators
- Don Branch, PhD, Principal investigator, Canadian Blood Services
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02259478
- Sponsor's protocol ID
- 14-8191-CE
- Status last verified
- Mar 2017
- First submitted
- 29 Aug 2014
- Last updated
- 14 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Elucidation of the Mechanism of IVIG-Associated Hemolysis
- ClinicalTrials.gov ID
- NCT02259478
- Acronym / sponsor ID
- 14-8191-CE
- Conditions
- Immunoglobulins, Intravenous, Hemolysis
- Keywords
- Intravenous Immunoglobulin (IVIG), Hemolysis, Transfusion Medicine, Pharmacovigilance
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 144 participants (actual)
- Lead sponsor
- Toronto Transfusion Medicine CollaborativeUniversity, hospital or other
- Collaborators
- University Health Network, Toronto, Sunnybrook Health Sciences Centre, Mount Sinai Hospital, New York, The Hospital for Sick Children, Unity Health Toronto, Women's College Hospital
- Study start
- Oct 2014
- Primary completion
- Oct 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 8 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
Who may qualify
- Ages
- 3 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Hemolysis
Time frame: From initiation of IVIG therapy to 5-10 days after the completion of last IVIG infusion
Definition and grading of hemolysis adopted from the Canadian IVIG Hemolysis Pharmacovigilance Group
2 secondary outcomes
Adverse transfusion reaction
Time frame: From initiation of IVIG therapy to 5-10 days after the completion of last IVIG infusion
Descriptive analysis of risk factors
Time frame: From initiation of IVIG therapy to 5-10 days after the completion of last IVIG infusion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2017.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Don Branch, PhD principal investigator
Canadian Blood Services
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Immunoglobulins, Intravenous and Hemolysis, run by Toronto Transfusion Medicine Collaborative at 6 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hemolysis (time frame: From initiation of IVIG therapy to 5-10 days after the completion of last IVIG infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2017.