Small-Volume Tubes to Reduce Anemia and Transfusion (STRATUS): A Pragmatic Stepped Wedge Cluster Randomized Trial
Authors: Siegal Deborah M , Belley-Cote Emilie , Arnold Donald M. , D'Aragon Frederick , Stephen Hill , Lee Shun Fu , Pinto Tara , Rochwerg Bram , Connolly Stuart J. , Zarychanski Ryan , Crowther Mark 
Published: November 2019

Background: Intensive care unit (ICU) patients undergo frequent blood sampling for laboratory testing resulting in blood loss that contributes to anemia and red blood cell (RBC) transfusion. Only 10% of the blood collected is used for testing suggesting that lower sample volumes may reduce the incidence/severity of anemia and use of RBC transfusion without compromising care.
Small-volume (soft-draw) Vacutainer® tubes for blood collection (2-3 mL) have the same cost, physical dimensions, and blood draw technique as standard-volume tubes (4-10 mL) and are compatible with laboratory analyzers. We previously conducted a mixed-methods pilot study (n=369) in which small-volume tubes were implemented in the ICU resulting in a 45% reduction in blood loss with acceptability to end-users and no increased frequency of inadequate samples.
We are currently conducting the STRATUS trial, a multi-center stepped wedge cluster randomized trial to determine whether a policy of using small-volume blood collection tubes reduces RBC transfusion compared to standard-volume tubes in adult ICU patients. Using this design an intervention can be incorporated into everyday practice at a site of care (such as an ICU) where individual randomization is not feasible. It is ideal for studying the effectiveness and implementation of interventions that have a high likelihood of benefit and low risk of harm.
Study Design and Methods: STRATUS is a pragmatic stepped wedge cluster randomized trial being conducted at 25 ICUs (clusters) in Canada over 18 months. At 6-week intervals (steps), 2 ICUs are randomly selected to switch from standard-volume tubes (control) to small-volume tubes (intervention) for blood sampling. All patients admitted to the ICU during the study period are enrolled with waived consent and undergo blood sampling using the allocated tubes. To be eligible for STRATUS, ICUs met the following criteria: (i) adult care only (≥18 years), (ii) unit size ≥14 beds, (iii) capacity for mechanical ventilation; (iv) use of standard-volume Vacutainer® blood collection tubes at baseline; and (v) availability of electronic administrative and laboratory information. The primary outcome is the number of RBC units transfused per patient during their ICU stay in patients admitted to ICU for ≥48 hours. Secondary outcomes include (i) number of RBC units transfused per patient for the entire cohort, (ii) percentage change in estimated blood loss; (iii) change in hemoglobin concentration from ICU admission to discharge adjusted for RBC transfusion; (iv) number of samples with inadequate volume for testing; (v) ICU and hospital mortality; and (vi) ICU and hospital length of stay. The study is approved by local and provincial research ethics boards. Data are collected from electronic administrative and health record sources. Assuming a power of 90% with a type I error of 5% (2-sided) and intra-cluster correlation coefficient (ICC) of 0.01, 25 sites with 729 patients per site (total 18,240 ICU patients) are required to detect a minimum difference of 5 units per 100 patients (or 2.5% reduction). As the interventions are applied in hospital, we expect minimal loss to follow-up. From trial initiation January 2, 2019 to August 1, 2019, 6 sites have been switched to small-volume blood collection tubes on schedule. Up to May 2, 2019 enrolment was 4,186 patients.
Significance: STRATUS will determine whether the use of small-volume blood collection tubes reduces RBC transfusion in ICU patients using an innovative cluster trial design that incorporates the intervention into routine ICU practice. With electronic administrative and health record data collection and a clinically relevant primary outcome, this pragmatic trial has the potential to change blood collection practices widely.

Disclosures
Siegal: Portola: Honoraria; BMS-Pfizer: Honoraria; Novartis: Honoraria; Bayer: Honoraria; Leo Pharma: Honoraria; Aspen Pharma: Honoraria. Arnold:Novartis: Honoraria, Research Funding; Rigel: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; Principia: Consultancy. Connolly:Bayer Healthcare: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Portola Pharmaceuticals: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding. Crowther:Octapharma: Membership on an entity's Board of Directors or advisory committees; Shionogi: Membership on an entity's Board of Directors or advisory committees; Alexion: Speakers Bureau; Asahi Kasei: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Other: preparing educational material and/or providing educational presentations; Pfizer: Other: preparing educational material and/or providing educational presentations; Servier Canada: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS Canada: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Other: Data and Safety Monitoring Board, Research Funding, Speakers Bureau; Diagnostica Stago: Other: preparing educational material and/or providing educational presentations, Research Funding; Alnylam: Equity Ownership.