TITRE - Clinician Site

TITRE is a multicenter, prospective, randomized clinical trial being conducted in the United States, Canada, and Australia. 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.

Why TITRE?

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:

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).

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.

What we will lean from TITRE

ELIGIBILITY

Can My Patient Participate?

Eligibility

Inclusion Criteria:

Age < 6 years at start of ECMO
Veno-arterial (VA) mode of ECMO
First ECMO run during your child’s hospital admission

Exclusion Criteria (child is not eligible if any one is met)

Combined gestational age + postnatal age < 37 weeks at the time of randomization
Sole purpose of ECMO is to provide procedural support
ECMO duration expected to be ≤24 hours
Veno-venous (VV) mode of ECMO
Initially started on VV-ECMO and then transitioned to VA ECMO
Limitation of care in place or being discussed
History of congenital bleeding disorder or a hemoglobinopathy
Primary residence outside the country of enrollment
Concurrent participation in a separate interventional trial that has the potential to impact neurodevelopmental status
Lack of access to medical records required for calculation of pre-ECMO pSOFA score due to cannulation for ECMO at a non-trial center..
Randomization not possible within 36 hours following ECMO cannulation (e.g., due to staffing or delays related to communication with participant family)
Planned transition to ventricular assist device (VAD) within 48 hours of commencing ECMO.
Clinically documented indication for a Red Blood Cell transfusion threshold that differs from the center-specific transfusion threshold (e.g., oncological treatment that limits donor exposure)

Trial at a Glance

Number of Sites: 22 large-volume pediatric ECMO centers

Coordinated by: Boston Children’s Hospital

Number of Patients to be Enrolled: 228

Accrual Period: 18 months

Follow-up per patient: 12 months

Trial Funding: U.S. Department of Defense

Trial Measurements

Key Outcomes measured during initial hospital admission:
- Change in pSOFA score
- Days on ECMO and mechanical ventilation
- Renal function
- Donor exposures/total blood volume received during ECMO
- Length of hospital and ICU stay
- Survival

Neurodevelopment & Quality of Life assessed 12 months after ECMO support:
- Bayley Scales of Infant and Toddler Development or Wechsler Preschool and Primary Scale of Intelligence
- Child behavior questionnaire (completed by parent/guardian)
- Health-related quality of life questionnaire (completed by parent/guardian at 9 mo)

FAQs

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.