Transfusion ReactionTADPOLNCT04267029
Transfusion Associated Dyspnea Profiling
An observational study of Transfusion Reaction, run by Toronto Transfusion Medicine Collaborative at 4 sites in Canada.
Trial summary
Transfusion reactions are defined as harms occurring during or after blood transfusion, with new heart/lung stress (eg. troubled breathing) regarded as cardiorespiratory transfusion reactions (CRTRs). CRTRs are among the most important, as the leading cause of transfusion-related harm and death. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Transfusion Reaction
- What is being tested?
- TADPOL battery (deep clinicolaboratory profile)
- How many people
- 151 participants
- Where
- 4 sitesCanada
- Study dates
- 1 Jan 2019to 22 Dec 2022
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adult patients at 4 university-affiliated teaching hospitals who have received a blood transfusion, and experienced a suspected acute transfusion reaction
Who may be able to join
- Age ≥ 18 years
- Transfusion of blood products (components or derivatives) with an available pre-transfusion group \& screen specimen
- Referred to the blood transfusion laboratory for review of a suspected acute transfusion reaction (occurring within 24 hours of completing transfusion), and either exhibiting a cardiorespiratory disturbance (CRTR: cases) or a high-risk febrile disturbance (HRFTR: controls)
Who cannot join
- Pregnant females
- Massive hemorrhage entailing >20 implicated products in the 24h period before the acute transfusion reaction's onset
- Previous enrolment in the same designation (ie- an individual with RTR will not re-enroll if having another RTR, but may re-enrol if having FTR)
- Expected to discharge home or die sooner than specimen acquisition
- Withdrawal of consent at any time
Trial locations and contacts
4 sites in 1 country.
Canada4 sites
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
University Health Network
Toronto, Ontario, M5G 2C4
Mount Sinai Hospital
Toronto, Ontario
St. Michael's Hospital
Toronto, Ontario
About this study
Official title: Transfusion-Associated Dyspnea: Prospective Observational and Laboratory Assessment
Transfusion reactions are defined as harms occurring during or after blood transfusion, with new heart/lung stress (eg. troubled breathing) regarded as cardiorespiratory transfusion reactions (CRTRs). CRTRs are among the most important, as the leading cause of transfusion-related harm and death. Though there are distinct classifications for these events, real life cases often don't fall neatly into a given category, with outliers regarded as "transfusion associated dyspnea (TAD)". It is unknown what TAD is -- whether it has a unique root cause, is a milder version of other known CRTRs, or is a blend of events. The purpose of this study is to better understand TAD and CRTRs by profiling them through a detailed medical history and more intensive laboratory assessment. This review of CRTRs may improve the quality/validity of final conclusions reported in the health record and to hemovigilance bodies, and uncover the nature of TAD and/or minimize CRTRs defaulting to the TAD category. Our enhanced understanding will advance diagnostic, treatment, and prevention efforts.
Read the detailed description
"Transfusion-Associated Dyspnea: Prospective Observation and Laboratory Assessment" (TADPOL) aims to improve the diagnosis and characterization of cardiorespiratory transfusion reaction (CRTR) patients ("cases"), as compared with high risk febrile transfusion reaction (HRFTR) patients ("controls"), by applying a standardized and intensive clinicolaboratory profiling tool.
CRTR, in contrast with HRFTR, are more difficult to diagnose and manage. Patients are often sick with (or prone to) pathologies that resemble reactions (eg. congestive heart failure [CHF] vs transfusion associated circulatory overload [TACO]), and/or experience more than one transfusion-associated disturbance at a time.
CRTRs are also the most disruptive, distressing, and disposition-escalating events for patients at an individual level, and are disproportionately accountable for transfusion associated deaths at the collective level in national hemovigilance systems. The cardinal CRTRs range from TACO (most commonly) to allergic bronchospasm to transfusion related acute lung injury (TRALI).
Inaccurate classification may undercount certain phenomena (when criteria fail to be met by confounding conditions), and/or overcount others (when including all possibilities-of-relevance in hemovigilance).
These uncertainties beget gaps (or excesses) in patient care and in donor/product-associated decision-making.
HYPOTHESES: The TADPOL CRF and laboratory profiling effort will improve the yields of confident (more certain), accurate (better-grounded), and thorough (multi-event-sensitive) diagnoses in CRTR patients.
Most cases of TAD are likely to be re-classified as milder versions (or overlaps) of possible CRTR states (± the underlying condition), while the remainder may exhibit a signature resembling FNHTR (FTR controls).
Precise case-mapping should yield useful personalized information, while aggregated findings from each disturbance pathway - as they are distributed in each conventional reaction category - can validate the utility of markers being explored in reaction investigation algorithms.
The TADPOL bioarchive and anonymized dataset will also be assets for explorations of novel indicators and patterns.
- Conditions
- Transfusion Reaction
- Being tested
- TADPOL battery (deep clinicolaboratory profile)
- Keywords
- TACO (transfusion associated circulatory overload), TRALI (transfusion related acute lung injury), Allergic Reaction, FNHTR (febrile non-hemolytic transfusion reaction), TAD (transfusion associated dyspnea)
- Medical subject headings
- Transfusion Reaction, Transfusion-Related Acute Lung Injury, Hypersensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TADPOL battery (deep clinicolaboratory profile)Diagnostic test
profile dimensions:
- hemolytic
- allergic
- cardiorenal
- inflammatory
- leukoagglutinating
- exploratory bioarchive
| Study group | Role | What they receive |
|---|---|---|
| Cases: CRTR (cardiorespiratory transfusion reaction) | Respiratory/cardiovascular disturbances after transfusion (>/=2 of respiratory distress, pulmonary edema, cardiovascular system changes, fluid shifts, cardiac strain indicators), with or without accompanying (or pre-existing) fever Receives: Diagnostic Test: TADPOL battery (deep clinicolaboratory profile) | |
| Controls: HRFTR (high risk febrile transfusion reactions) | Post-transfusion fevers requiring laboratory investigation (Tmax>/=39C, or lesser deflections if accompanied by chills/rigors), without respiratory features (hypoxia or dyspnea) Receives: Diagnostic Test: TADPOL battery (deep clinicolaboratory profile) |
What is being measured
The primary outcome is the main question the study is designed to answer.
CERTAINTY
Improve certainty in final cardiorespiratory transfusion reaction event classifications (by reduction in the number of cases otherwise achieving no better than "possible" provisional conclusions), from the expected base ambiguity rate of 60%, down to 30%.
Measured: 2 years
Secondary outcomes (2)
COMPLEXITY
Determine the frequency of multi-domain disturbances (ie- "overlap") in cardiorespiratory transfusion reaction referrals
Measured: 2 years
PATHOGENESIS FOOTPRINTING
Statistically characterize concordance of established and potential criteria in TRALI, TACO, allergic bronchospasm, and TAD
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2020
- Study start1 Jan 2019
- Primary completion4 Oct 2022
- Study completion22 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Transfusion ReactionStudies 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
- 151 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, Unity Health Toronto, Canadian Blood Services
- Responsible party
- Sponsor
- Investigators
- Christine M Csert-Gazdewich, MD, Principal investigator, Universith Health Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04267029
- Sponsor's protocol ID
- TADPOL_v0.7
- Acronym
- TADPOL
- Status last verified
- Apr 2023
- First submitted
- 7 Feb 2020
- Last updated
- 3 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Callum JL, Cohen R, Cressman AM, Strauss R, Armali C, Lin Y, Pendergrast J, Lieberman L, Scales DC, Skeate R, Ross H, Cserti-Gazdewich C. Cardiac stress biomarkers after red blood cell transfusion in patients at risk for transfusion-associated circulatory overload: a prospective observational study. Transfusion. 2018 Sep;58(9):2139-2148. doi: 10.1111/trf.14820.
PubMed 30204946Cohen R, Escorcia A, Tasmin F, Lima A, Lin Y, Lieberman L, Pendergrast J, Callum J, Cserti-Gazdewich C. Feeling the burn: the significant burden of febrile nonhemolytic transfusion reactions. Transfusion. 2017 Jul;57(7):1674-1683. doi: 10.1111/trf.14099. Epub 2017 Mar 28.
PubMed 28369916Parmar N, Pendergrast J, Lieberman L, Lin Y, Callum J, Cserti-Gazdewich C. The association of fever with transfusion-associated circulatory overload. Vox Sang. 2017 Jan;112(1):70-78. doi: 10.1111/vox.12473. Epub 2016 Dec 21.
PubMed 28001310McVey MJ, Cohen R, Arsenault V, Escorcia A, Tasmin F, Pendergrast J, Lieberman L, Lin Y, Callum J, Cserti-Gazdewich C. Frequency and timing of all-cause deaths in visits involving suspected transfusion reactions, and the significance of cardiopulmonary disturbances. Vox Sang. 2021 Sep;116(8):898-909. doi: 10.1111/vox.13086. Epub 2021 Feb 26.
PubMed 33634884
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transfusion-Associated Dyspnea: Prospective Observational and Laboratory Assessment
- ClinicalTrials.gov ID
- NCT04267029
- Acronym / sponsor ID
- TADPOL / TADPOL_v0.7
- Conditions
- Transfusion Reaction
- Keywords
- TACO (transfusion associated circulatory overload), TRALI (transfusion related acute lung injury), Allergic Reaction, FNHTR (febrile non-hemolytic transfusion reaction), TAD (transfusion associated dyspnea)
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 151 participants (actual)
- Lead sponsor
- Toronto Transfusion Medicine CollaborativeUniversity, hospital or other
- Collaborators
- University Health Network, Toronto, Sunnybrook Health Sciences Centre, MOUNT SINAI HOSPITAL, Unity Health Toronto, Canadian Blood Services
- Study start
- 1 Jan 2019 (actual)
- Primary completion
- 4 Oct 2022 (actual)
- Study completion
- 22 Dec 2022 (actual)
- First posted
- 12 Feb 2020 (actual)
- 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.
Transfusion reactions are defined as harms occurring during or after blood transfusion, with new heart/lung stress (eg. troubled breathing) regarded as cardiorespiratory transfusion reactions (CRTRs). CRTRs are among the most important, as the leading cause of transfusion-related harm and death. Though there are distinct classifications for these events, real life cases often don't fall neatly into a given category, with outliers regarded as "transfusion associated dyspnea (TAD)". It is unknown what TAD is -- whether it has a unique root cause, is a milder version of other known CRTRs, or is a blend of events. The purpose of this study is to better understand TAD and CRTRs by profiling them through a detailed medical history and more intensive laboratory assessment. This review of CRTRs may improve the quality/validity of final conclusions reported in the health record and to hemovigilance bodies, and uncover the nature of TAD and/or minimize CRTRs defaulting to the TAD category. Our enhanced understanding will advance diagnostic, treatment, and prevention efforts.
Detailed description
"Transfusion-Associated Dyspnea: Prospective Observation and Laboratory Assessment" (TADPOL) aims to improve the diagnosis and characterization of cardiorespiratory transfusion reaction (CRTR) patients ("cases"), as compared with high risk febrile transfusion reaction (HRFTR) patients ("controls"), by applying a standardized and intensive clinicolaboratory profiling tool.
CRTR, in contrast with HRFTR, are more difficult to diagnose and manage. Patients are often sick with (or prone to) pathologies that resemble reactions (eg. congestive heart failure [CHF] vs transfusion associated circulatory overload [TACO]), and/or experience more than one transfusion-associated disturbance at a time.
CRTRs are also the most disruptive, distressing, and disposition-escalating events for patients at an individual level, and are disproportionately accountable for transfusion associated deaths at the collective level in national hemovigilance systems. The cardinal CRTRs range from TACO (most commonly) to allergic bronchospasm to transfusion related acute lung injury (TRALI).
Inaccurate classification may undercount certain phenomena (when criteria fail to be met by confounding conditions), and/or overcount others (when including all possibilities-of-relevance in hemovigilance).
These uncertainties beget gaps (or excesses) in patient care and in donor/product-associated decision-making.
HYPOTHESES: The TADPOL CRF and laboratory profiling effort will improve the yields of confident (more certain), accurate (better-grounded), and thorough (multi-event-sensitive) diagnoses in CRTR patients.
Most cases of TAD are likely to be re-classified as milder versions (or overlaps) of possible CRTR states (± the underlying condition), while the remainder may exhibit a signature resembling FNHTR (FTR controls).
Precise case-mapping should yield useful personalized information, while aggregated findings from each disturbance pathway - as they are distributed in each conventional reaction category - can validate the utility of markers being explored in reaction investigation algorithms.
The TADPOL bioarchive and anonymized dataset will also be assets for explorations of novel indicators and patterns.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cases: CRTR (cardiorespiratory transfusion reaction) | – | Diagnostic Test: TADPOL battery (deep clinicolaboratory profile)Respiratory/cardiovascular disturbances after transfusion (>/=2 of respiratory distress, pulmonary edema, cardiovascular system changes, fluid shifts, cardiac strain indicators), with or without accompanying (or pre-existing) fever |
| Controls: HRFTR (high risk febrile transfusion reactions) | – | Diagnostic Test: TADPOL battery (deep clinicolaboratory profile)Post-transfusion fevers requiring laboratory investigation (Tmax>/=39C, or lesser deflections if accompanied by chills/rigors), without respiratory features (hypoxia or dyspnea) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult patients at 4 university-affiliated teaching hospitals who have received a blood transfusion, and experienced a suspected acute transfusion reaction
Key inclusion criteria (3 listed)
- Age ≥ 18 years
- Transfusion of blood products (components or derivatives) with an available pre-transfusion group \& screen specimen
- Referred to the blood transfusion laboratory for review of a suspected acute transfusion reaction (occurring within 24 hours of completing transfusion), and either exhibiting a cardiorespiratory disturbance (CRTR: cases) or a high-risk febrile disturbance (HRFTR: controls)
Key exclusion criteria (5 listed)
- Pregnant females
- Massive hemorrhage entailing >20 implicated products in the 24h period before the acute transfusion reaction's onset
- Previous enrolment in the same designation (ie- an individual with RTR will not re-enroll if having another RTR, but may re-enrol if having FTR)
- Expected to discharge home or die sooner than specimen acquisition
- Withdrawal of consent at any time
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TADPOL battery (deep clinicolaboratory profile)profile dimensions: * hemolytic * allergic * cardiorenal * inflammatory * leukoagglutinating * exploratory bioarchive | Diagnostic test | Cases: CRTR (cardiorespiratory transfusion reaction), Controls: HRFTR (high risk febrile transfusion reactions) |
Primary outcome
CERTAINTY
Time frame: 2 years
Improve certainty in final cardiorespiratory transfusion reaction event classifications (by reduction in the number of cases otherwise achieving no better than "possible" provisional conclusions), from the expected base ambiguity rate of 60%, down to 30%.
2 secondary outcomes
COMPLEXITY
Time frame: 2 years
PATHOGENESIS FOOTPRINTING
Time frame: 2 years
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 3 May 2023.
- Background: PubMed 30204946Callum JL, Cohen R, Cressman AM, Strauss R, Armali C, Lin Y, Pendergrast J, Lieberman L, Scales DC, Skeate R, Ross H, Cserti-Gazdewich C. Cardiac stress biomarkers after red blood cell transfusion in patients at risk for transfusion-associated circulatory overload: a prospective observational study. Transfusion. 2018 Sep;58(9):2139-2148. doi: 10.1111/trf.14820.
- Background: PubMed 28369916Cohen R, Escorcia A, Tasmin F, Lima A, Lin Y, Lieberman L, Pendergrast J, Callum J, Cserti-Gazdewich C. Feeling the burn: the significant burden of febrile nonhemolytic transfusion reactions. Transfusion. 2017 Jul;57(7):1674-1683. doi: 10.1111/trf.14099. Epub 2017 Mar 28.
- Background: PubMed 28001310Parmar N, Pendergrast J, Lieberman L, Lin Y, Callum J, Cserti-Gazdewich C. The association of fever with transfusion-associated circulatory overload. Vox Sang. 2017 Jan;112(1):70-78. doi: 10.1111/vox.12473. Epub 2016 Dec 21.
- Background: PubMed 33634884McVey MJ, Cohen R, Arsenault V, Escorcia A, Tasmin F, Pendergrast J, Lieberman L, Lin Y, Callum J, Cserti-Gazdewich C. Frequency and timing of all-cause deaths in visits involving suspected transfusion reactions, and the significance of cardiopulmonary disturbances. Vox Sang. 2021 Sep;116(8):898-909. doi: 10.1111/vox.13086. Epub 2021 Feb 26.
- TADPOL Protocol paperLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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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.
Christine M Csert-Gazdewich, MD principal investigator
Universith Health Network
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Transfusion Reaction, run by Toronto Transfusion Medicine Collaborative at 4 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 3 inclusion and 5 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 3 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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?
CERTAINTY (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04267029, which also lists 4 linked publications.
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 3 May 2023.