Pilot Optimizing Transfusion Thresholds in Critically-ill Children With Anaemia

NCT ID: NCT03871244

Last Updated: 2021-09-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-03
• Study Completion Date: 2022-12-31

Brief Summary

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.

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.

Conditions

Anemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Less red blood cell transfusions

Intervention Type: PROCEDURE

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.

Standard care arm (comparator)

Clinical teams will follow their usual transfusion practices.

Group Type: ACTIVE_COMPARATOR

More red blood cell transfusion (standard transfusion strategy in PICU)

Intervention Type: PROCEDURE

The instructions given to caregivers will be to prescribe a red blood cell transfusion according to their usual standard practice

Interventions

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.

Intervention Type: 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

Intervention Type: PROCEDURE

Other Intervention Names

Restrictive red blood cell transfusion strategy

Eligibility Criteria

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)

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oxford University Hospitals NHS Trust

OTHER

Sponsor Role: collaborator

Hôpital Jeanne de Flandre

UNKNOWN

Sponsor Role: collaborator

NHS Blood and Transplant

OTHER_GOV

Sponsor Role: collaborator

St. Justine's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jacques Lacroix, MD, FRCPC, Professor

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jacques Lacroix

Role: PRINCIPAL_INVESTIGATOR

St-Justine Hospital Center

Locations

CHU Sainte-Justine

Montreal, Quebec, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Jacques Lacroix

Role: CONTACT

jacques.lacroix.med@ssss.gouv.qc.ca

514-345-4931 ext. 5556

Josee Poirier

Role: CONTACT

josee.poirier.hsj@ssss.gouv.qc.ca

514-345-4931 ext. 4053

Facility Contacts

Josée Poirier

Role: primary

josee.poirier.hsj@ssss.gouv.qc.ca

514-345-4931 ext. 4053

References

Carson JL, Stanworth SJ, Dennis JA, Fergusson DA, Pagano MB, Roubinian NH, Turgeon AF, Valentine S, Trivella M, Doree C, Hebert PC. Transfusion thresholds and other strategies for guiding red blood cell transfusion. Cochrane Database Syst Rev. 2025 Oct 20;10:CD002042. doi: 10.1002/14651858.CD002042.pub6.

Reference Type: DERIVED

PMID: 41114449 (View on PubMed)

Tucci M, Sarfatti A, Leteurtre S, Du Pont-Thibodeau G, Fontela P, Ray S, Stanworth SJ, Hebert PC, Roumeliotis N, Sauthier M, Spinella PC, Ducruet T, Jouvet P, Masse B, Robitaille N, Trottier H, Lacroix J; Canadian Critical Care Trials Group and the Groupe Francophone de Reanimation et d'Urgences Pediatriques. Pilot-Optimizing Transfusion Therapy in Critically Ill Children With Anemia: A Pilot Multicenter Electronic Health Record-Enabled Randomized Controlled Trial on Red Blood Cell Transfusion in Critically Ill Children. Pediatr Crit Care Med. 2025 Oct 1;26(10):e1218-e1230. doi: 10.1097/PCC.0000000000003822. Epub 2025 Sep 12.

Reference Type: DERIVED

PMID: 40938139 (View on PubMed)

Radford M, Estcourt LJ, Sirotich E, Pitre T, Britto J, Watson M, Brunskill SJ, Fergusson DA, Doree C, Arnold DM. Restrictive versus liberal red blood cell transfusion strategies for people with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without haematopoietic stem cell support. Cochrane Database Syst Rev. 2024 May 23;5(5):CD011305. doi: 10.1002/14651858.CD011305.pub3.

Reference Type: DERIVED

PMID: 38780066 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34932836 (View on PubMed)

Other Identifiers

MP-21-2019-2235

Identifier Type: -

Identifier Source: org_study_id