Cluster-Randomized Trial of Thrombolysis Implementation Support in Metropolitan and Regional Australian Stroke Centers: Lessons for Individual and Systems Behavior Change

Abstract

Background Intravenous thrombolytic therapy (IVT) with tissue plasminogen activator for acute ischemic stroke is underutilized in many parts of the world. Randomized trials to test the effectiveness of thrombolysis implementation strategies are limited. Methods and Results This study aimed to test the effectiveness of a multicomponent, multidisciplinary tissue plasminogen activator implementation package in increasing the proportion of thrombolyzed cases while maintaining accepted benchmarks for low rates of intracranial hemorrhage and high rates of functional outcomes at 3 months. A cluster randomized controlled trial of 20 hospitals in the early stages of thrombolysis implementation across 3 Australian states was undertaken. Monitoring of IVT rates during the baseline period allowed hospitals (the unit of randomization) to be grouped into 3 baseline IVT strata-very low rates (0% to ≤4.0%); low rates (>4.0% to ≤10.0%); and moderate rates (>10.0%). Hospitals were randomized to an implementation package (experimental group) or usual care (control group) using a 1:1 ratio. The 16-month intervention was based on behavioral theory and analysis of the steps, roles, and barriers to rapid assessment for thrombolysis eligibility and involved comprehensive strategies addressing individual and system-level change. The primary outcome was the difference in tissue plasminogen activator proportions between the 2 groups postintervention. The absolute difference in postintervention IVT rates between intervention and control hospitals adjusted for baseline IVT rate and stratum was not significant (primary outcome rate difference=1.1% (95% CI -1.5% to 3.7%; P=0.38). Rates of intracranial hemorrhage remained below international benchmarks. Conclusions The implementation package resulted in no significant change in tissue plasminogen activator implementation, suggesting that ongoing support is needed to sustain initial modifications in behavior. Clinical Trial Registration URL: www.anzctr.org.au Unique identifiers: ACTRN12613000939796 and U1111-1145-6762.

Keywords: health system change; implementation; ischemic stroke; quality improvement; thrombolysis.

Figure 1

Intervention elements and time frames. *Data collected from March 2014 onwards. NB: Gray boxes indicate that the activity was undertaken in that month. Functions are included in brackets. PCA is 1 or more members of the RT. FTF indicates face to face; PCA, primary change agent; RT, research team; SC, site champions (usually lead nurse and lead clinician); tPA, tissue plasminogen activator; WG, working group.

Figure 2

Trial profile. Baseline, January 2011 to August 2013; intervention, September 2013 to December 2014; follow‐up, January to December 2015. tPA indicates tissue plasminogen activator.

Figure 3

Differences in intravenous thrombolysis rates between intervention and control hospitals over time. (*rate difference intervention to control P < 0.05).

Figure 4

Intravenous thrombolysis rate ratios and 95% CIs over the intervention and postintervention time periods.