Patients in paediatric intensive care units (PICU) are among the main groups of transfusion
recipients. Blood transfusions expose recipients to infectious and non-infectious serious
hazards. Despite an increasing number of red blood cell (RBC) transfusion threshold
randomised controlled trials (RCT) to date, only one large RCT, the Transfusion Requirement
In PICU (TRIPICU) study (Lacroix. N Engl J Med 2007;356:1609-19) informs practice in PICU.
This dearth of paediatric data was reiterated by a recent National Heart, Lung and Blood
Institutes state of the art symposium. Despite being internally robust, the generalizability
of TRIPICU has been questioned given that nearly 90% of critically ill children with
haemoglobin (Hb) level ≤ 95 g/L were not enrolled for a range of pre-specified reasons
including severity of illness, clinical instability and uncertain physician buy-in, thus
threatening broader application of this critical knowledge into practice. Recent data and
evidence summarised in systematic reviews support the need to explore the benefits and safety
of Hb threshold ≤ 70 g/L for almost all critically ill children, not only those who would
have been enrolled in TRIPICU.
We propose an international pilot study that will inform the design of a large pragmatic
non-inferiority RCT (termed OpTTICCA) conceived to derive generalizable transfusion guidance
for physicians.
Objectives of the pilot-RCT. Specific aims are to:
Establish the feasibility of enrolling ≥80% of eligible patients.
Document adherence to study intervention ≥80% (restrictive transfusion policy).
Assess the incidence rate of the primary outcome measure of the full RCT (new and
progressive multiple organ dysfunction syndrome, which includes mortality).
Establish the feasibility of using routinely collected clinical information from
electronic medical data monitoring system (eMDMS) to enhance cost-efficiency.
In the pilot-RCT, we will enrol 120 patients (20 to 40/site) in PICUs equipped with
electronic medical data monitoring system (eMDMS). This trial builds on successful prior RCTs
that involved international collaboration and funding (Canada, United Kingdom, France):
TRIPICU, Age of Blood Evaluation (ABLE) (Lacroix. N Engl J Med 2015) and Age of Blood in
Children in PICU (ABC-PICU study: Tucci et al. Trials 2018). The pilot-RCT will be considered
as the vanguard phase of the full OpTTICCA RCT if no important design changes are required.
Expected results. This pilot-RCT will focus on feasibility parameters. It will explore
whether we can 1) recruit a much broader eligible patient group, 2) assess protocol
adherence, 3) assess the primary outcome measure, and 4) abstract most data electronically. A
definitive trial will provide transfusion guidance for many important subgroups in whom
evidence is presently lacking including children admitted with bone marrow failure, head
injury, some cardiac disorders, and sepsis.
