Pilot Optimizing Transfusion Thresholds in Critically-ill Children With Anaemia

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.

Sponsors

Lead Sponsor: St. Justine's Hospital

Source St. Justine's Hospital
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.

Overall Status Not yet recruiting
Start Date October 31, 2019
Completion Date September 2020
Primary Completion Date June 2020
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Recruitment: screening One year
Recruitment: consent One year
Recruitment: enrolment One year
Secondary Outcome
Measure Time Frame
Representativeness: exclusion One year
Representativeness: opt-out One year
Compliance One year
Separation One year
Suspension One year
Data collection One year
Data entry One year.
Outcomes One year.
Enrollment 120
Condition
Intervention

Intervention Type: Procedure

Intervention Name: Less red blood cell transfusions

Description: 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.

Arm Group Label: Restrictive arm (intervention)

Other Name: Restrictive red blood cell transfusion strategy

Intervention Type: Procedure

Intervention Name: More red blood cell transfusion (standard transfusion strategy in PICU)

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

Arm Group Label: Standard care arm (comparator)

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)

Gender: All

Minimum Age: N/A

Maximum Age: 18 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Jacques Lacroix Principal Investigator St-Justine Hospital Center
Overall Contact

Last Name: Jacques Lacroix

Phone: 514-345-4931

Phone Ext.: 5556

Email: [email protected]

Verification Date

October 2019

Responsible Party

Type: Principal Investigator

Investigator Affiliation: St. Justine's Hospital

Investigator Full Name: Jacques Lacroix, MD, FRCPC, Professor

Investigator Title: Professor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Restrictive arm (intervention)

Type: Experimental

Description: 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.

Label: Standard care arm (comparator)

Type: Active Comparator

Description: Clinical teams will follow their usual transfusion practices.

Acronym P-OpTTICCA
Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Intervention Model Description: parallel open-label pragmatic non-inferiority randomised controlled trial (RCT)

Primary Purpose: Treatment

Masking: Double (Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov