Pilot Optimizing Transfusion Thresholds in Critically-ill Children With Anaemia (P-OpTTICCA)

Pilot Optimizing Transfusion Thresholds in Critically-ill Children With Anaemia (P-OpTTICCA): a Pilot Trial for a Large Pragmatic International Parallel Open-label Non-inferiority Randomised Controlled Trial.

The Pilot Optimizing Transfusion Thresholds in Critically-ill Children with Anaemia (P-OpTTICCA) study is a pilot trial for a large pragmatic international parallel open-label non-inferiority randomised controlled trial. The primary outcome of the pilot study is feasibility.

Study Overview

• Status: Recruiting
• Conditions: Anemia
• Intervention / Treatment: Procedure: Less red blood cell transfusions; Procedure: More red blood cell transfusion (standard transfusion strategy in PICU)

Detailed Description

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:

1. Establish the feasibility of enrolling ≥80% of eligible patients.
2. Document adherence to study intervention ≥80% (restrictive transfusion policy).
3. Assess the incidence rate of the primary outcome measure of the full RCT (new and progressive multiple organ dysfunction syndrome, which includes mortality).
4. 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.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jacques Lacroix; Phone Number: 5556 514-345-4931; Email: jacques.lacroix.med@ssss.gouv.qc.ca
• Study Contact Backup: Name: Josée Poirier; Phone Number: 4053 514-345-4931; Email: josee.poirier.hsj@ssss.gouv.qc.ca

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H3T 1C5
      • Recruiting
      • CHU Sainte-Justine
      • Contact: Josée Poirier; Phone Number: 4053 514-345-4931; Email: josee.poirier.hsj@ssss.gouv.qc.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 1. Hemoglobin concentration ≤ 95 g/L, while in PICU
• 2. Not already participating to a randomized controlled trial on hemoglobin threshold to guide red blood cell transfusion practice

Exclusion Criteria:

1. Post conception age ≤ 36 weeks or > 18 years at PICU entry
2. Refusal of consent by patient and/or parent
3. Uncorrected cyanotic cardiac disease, univentricular physiology
4. Sickle cell disease
5. Brain Death
6. Extracorporeal membrane oxygenation (ECMO)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Restrictive arm (intervention); Less red blood cell transfusions. The protocol will require that no red blood cell transfusion be given unless the hemoglobin level is below or equal at 70 g per L.	Procedure: Less red blood cell transfusions; The instructions given to caregivers will be to consider prescribing a red blood cell transfusion only if the hemoglobin level is ≤ 70 g per L.; Other Names: Restrictive red blood cell transfusion strategy
Active Comparator: Standard care arm (comparator); Clinical teams will follow their usual transfusion practices.	Procedure: More red blood cell transfusion (standard transfusion strategy in PICU); The instructions given to caregivers will be to prescribe a red blood cell transfusion according to their usual standard practice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment: screening	Proportion of patients eligible for consent approached > 90%;	One year
Recruitment: consent	Proportion of approached patients who decline consent < 20%,	One year
Recruitment: enrolment	Recruitment: ≥ 2 patients randomized/site/week.	One year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Representativeness: exclusion	We recruit > 80% of patients who would have been excluded from TRIPICU (Lacroix et al. N Engl Med 2007).	One year
Representativeness: opt-out	Proportion of dropout and lost to follow-up is expected to be < 2%.	One year
Compliance	Proportion of RBC transfusions given with hemoglobin > 70 g/L in the restrictive arm (definition of non-compliance) is < 20%.	One year
Separation	Post randomisation separation of hemoglobin concentration between both arms in the pilot-RCT is ≥ 10 g/L.	One year
Suspension	Proportion of children wha are suspended is < 20%.	One year
Data collection	Most data (> 80%) are abstracted directly from electronic medical data monitoring system.	One year
Data entry	Proportion of erroneous data entry is < 5%.	One year.
Outcomes	Incidence rate of the primary outcome measure - new and progressive multiple organ dysfunction syndrome (NPMODS) - in the standard care arm of the pilot-trial is ≥ 20%.	One year.

Collaborators and Investigators

• Sponsor: St. Justine's Hospital
• Collaborators: Oxford University Hospitals NHS Trust; NHS Blood and Transplant; Hôpital Jeanne de Flandre
• Investigators: Principal Investigator: Jacques Lacroix, St-Justine Hospital Center

Publications and helpful links

General Publications

• Carson JL, Stanworth SJ, Dennis JA, Trivella M, Roubinian N, Fergusson DA, Triulzi D, Doree C, Hebert PC. Transfusion thresholds for guiding red blood cell transfusion. Cochrane Database Syst Rev. 2021 Dec 21;12(12):CD002042. doi: 10.1002/14651858.CD002042.pub5.

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2020
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: March 6, 2019
• First Submitted That Met QC Criteria: March 8, 2019
• First Posted (Actual): March 12, 2019

Study Record Updates

• Last Update Posted (Actual): September 28, 2021
• Last Update Submitted That Met QC Criteria: September 22, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: randomized controlled trial; critically ill children; hemoglobin threshold; red blood cell tranfusions
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Hematologic Diseases; Critical Illness; Anemia
• Other Study ID Numbers: MP-21-2019-2235

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The data of P-OpTTICCA will be integrated in the large trial if possible. This will not be possible if P-OpTTICCA shows that significant changes must be made to the research proposal of the full trial; then the data of participants of P-OpTTICCA will be merged to the data of the full trial using a meta-analysis strategy.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No