TITRE - Clinician Site
TITRE is a multicenter, prospective, randomized clinical trial being conducted in the United States and Canada. The overarching goal of TITRE is to determine whether restricting RBC transfusion according to an indication-based strategy for those with bleeding and/or deficit of tissue oxygen delivery, compared with transfusion based on center-specific Hb or HCT thresholds, can reduce organ dysfunction, and improve later neurodevelopment in critically ill children receiving ECMO support.
Why TITRE?
Extracorporeal membrane oxygenation (ECMO) can provide life-saving mechanical cardiac and respiratory support to critically ill children, but only about half of all patients (50%) survive to go home after ECMO. Complications are common and long-term function including quality of life is compromised in many ECMO survivors. TITRE - Trial of Indication-based Transfusion of Red Blood Cells in ECMO, is a multicenter, prospective, randomized clinical trial being conducted to determine whether there is a better way to care for children receiving this invasive support.
What Will We Learn from TITRE?
The overarching goal of TITRE is to determine whether restricting RBC transfusion can reduce organ dysfunction, and improve later neurodevelopment in critically ill children receiving ECMO support. The TITRE trial hopes to answer two important scientific questions that will improve the outcomes of children on ECMO:
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Question 1: To determine whether children < 6 years of age on ECMO support who are randomly assigned to a strategy of indication-based versus center-specific threshold-based RBC transfusion will have greater improvement in organ function, as defined by the baseline-adjusted change in Pediatric Sequential Organ Failure Score (pSOFA).
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Question 2: To determine whether survivors among children age < 6 years on ECMO support who are randomly assigned to indication-based compared to center-specific threshold-based RBC transfusion will have better neurodevelopmental outcomes and health-related quality of life at one year post-randomization.
ELIGIBILITY
Can My Patient Participate?
Inclusion Criteria:
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Age < 6 years at start of ECMO
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Veno-arterial (VA) mode of ECMO
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First ECMO run during your child’s hospital admission
Exclusion Criteria (child is not eligible if any one is met)
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Combined gestational age + postnatal age < 37 weeks at the time of randomization
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Sole purpose of ECMO is to provide procedural support
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ECMO duration expected to be ≤24 hours
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Veno-venous (VV) mode of ECMO
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Initially started on VV-ECMO and then transitioned to VA ECMO
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Limitation of care in place or being discussed
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History of congenital bleeding disorder or a hemoglobinopathy
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Primary residence outside the country of enrollment
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Concurrent participation in a separate interventional trial that has the potential to impact neurodevelopmental status
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Lack of access to medical records required for calculation of pre-ECMO pSOFA score due to cannulation for ECMO at a non-trial center..
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Randomization not possible within 36 hours following ECMO cannulation (e.g., due to staffing or delays related to communication with participant family)
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Planned transition to ventricular assist device (VAD) within 48 hours of commencing ECMO.
Trial at a Glance
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Number of Sites: 22 large-volume pediatric ECMO centers
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Coordinated by: Boston Children’s Hospital
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Number of Patients to be Enrolled: 228
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Accrual Period: 18 months
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Follow-up per patient: 12 months
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Trial Funding: U.S. Department of Defense
Trial Measurements
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Key Outcomes measured during initial hospital admission:
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Change in pSOFA score
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Days on ECMO and mechanical ventilation
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Renal function
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Donor exposures/total blood volume received during ECMO
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Length of hospital and ICU stay
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Survival
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Neurodevelopment & Quality of Life assessed 12 months after ECMO support:
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Bayley Scales of Infant and Toddler Development or Wechsler Preschool and Primary Scale of Intelligence
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Child behavior questionnaire (completed by parent/guardian)
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Health-related quality of life questionnaire (completed by parent/guardian at 9 mo)
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FREQUENTLY ASKED QUESTIONS
Is it possible to leave the study early?
Yes. It is up to the child's family to decide to be in the study. Once in, you may leave the study at any time. Being in the study, or choosing to leave the study, will not affect other medical care at any time.
Will my privacy be protected?
We take confidentiality very seriously, and will ensure that your right to privacy is protected, and participation in this research study will remain confidential. No names or other identifying information will be used in any published report of information from this study.
How long will I be in the study?
Participants are followed for 12 months after enrollment.
Will the results of the study be shared?
We plan to publish what we find out from the study, so we can share this important information with families, researchers, and health care providers. Publications will be announced on this website, and will be communicated through study sites.
What will happen in this research study?
The study lasts 12 months. As part of the study, participants will be randomly assigned to receive blood transfusions according to usual care at the center, or according to the study protocol. We will gather information from participants’ medical records and reach out to participants every 2-3 months after hospital discharge to see how participants’ are doing. Participants will have one additional clinical visit at 12 months after ECMO for neurodevelopmental measurement.
Is there any cost to participate?
Tests that are done for research that are not part of regular care will be provided free of charge. Participants and families will be compensated for time and effort.
Publications
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Publications will be announced here. Please check back soon!
STUDY TEAM
TITRE Trial Leadership
Clinical Coordinating Center
Ravi Thiagarajan, MBBS, MPH
Trial Co-Chair
Jane Newburger, MD, MPH
Neurodevelopment/Investigator
Peta Alexander, MBBS
Trial Co-Chair
Daniel Kelly, MD, MHQS
Transfusion Medicine/Co-Investigator
Data & Statistical Coordinating Center
Lynn Sleeper, ScD
Grant PI & DCC PI
Anjali Sadhwani, PhD
Neurodevelopment Core/
Co-Investigator
David Bellinger, PhD
Director, Neurodevelopment Core
Melania Bembea, MD, PhD
Medical Monitor
(Johns Hopkins University)
Executive Committee
Heidi Dalton, MD
Inova Children’s Hospital
Marie Steiner, MD, MS
University of Minnesota
Philip Spinella, MD
University of Pittsburgh
Jennifer Muszynski, MD, MPH
Nationwide Children’s Hospital
Christopher Almond, MD, MPH
Lucile Packard Children’s Hospital
Adjudication Committee
Joanne Starr, MD
Children’s Hospital of Orange County
Marianne Nellis, MD, MS
Weill Cornell Medical College
Stacey Valentine, MD, MPH
Univ. of Massachusetts Chan Medical School
Site Principal Investigators