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Completed

NCT Number: NCT04267029

Transfusion Associated Dyspnea Profiling

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Mount Sinai Hospital, Toronto, Ontario, Canada

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About this study

"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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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)

Exclusion criteria

  • 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

Treatment and study plan

TADPOL battery (deep clinicolaboratory profile)

Diagnostic Test

profile dimensions:

  • hemolytic
  • allergic
  • cardiorenal
  • inflammatory
  • leukoagglutinating
  • exploratory bioarchive

Primary outcomes

  1. 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%.

Secondary outcomes

  1. COMPLEXITY

    Time frame: 2 years

    Determine the frequency of multi-domain disturbances (ie- "overlap") in cardiorespiratory transfusion reaction referrals

  2. PATHOGENESIS FOOTPRINTING

    Time frame: 2 years

    Statistically characterize concordance of established and potential criteria in TRALI, TACO, allergic bronchospasm, and TAD

Sponsors and collaborators

Lead sponsor

Toronto Transfusion Medicine Collaborative

Other

Collaborators

  • Canadian Blood Services
  • MOUNT SINAI HOSPITAL
  • Sunnybrook Health Sciences Centre
  • Unity Health Toronto
  • University Health Network, Toronto

Registry information

Official study title

Transfusion-Associated Dyspnea: Prospective Observational and Laboratory Assessment

Acronym: TADPOL

Important dates

Study start
2019
Primary completion
2022
Study completion
2022
First posted
Feb 12, 2020
Registry last updated
May 3, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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