Cluster‐Randomized Trial of Thrombolysis Implementation Support in Metropolitan and Regional Australian Stroke Centers: Lessons for Individual and Systems Behavior Change
Authors: Levi Christopher R. , Attia John A. , D'Este Cate , Ryan Annika E. , Henskens Frans , Kerr Erin , Parsons Mark W. , Sanson‐Fisher Robert W. , Bladin Christopher F. , Lindley Richard I. , Middleton Sandy , Paul Christine L. , Anderson Craig , Ang Tim , Bivard Andrew , Cadigan Greg , Celestino Sherisse , Coles Tim , Corbett Alistair , Dark Lisa , Day Susan , Dennett Jennifer , Donnan Geoffrey , Evans Malcolm , Fernando Kavisha , Geraghty Richard , Gerraty Richard , Grady Alice , Grimley Rohan , Gu Jason , Hankey Graeme J. , Hoffman Kim , Hughes James , Ip Jerome , Jenkins Bronwyn , Jones Mark , Jude Martin , Kaauwai Lara , Kanard Malcolm , Kinchington Matthew , Krause Martin , Kuhle Sarah , Levy Stanley , Longworth Mark , Macdonald Beverley , Mackey Elizabeth , Mandaleson Krishna , Miteff Ferdi , Mohr Katherine , Moore Stephen , Morris Kristy , O'Brien Elizabeth , Oldmeadow Christopher , Paddock Bruce , Parrey Kim , Peake Rachel , Russell Michelle , Stevenson Margaret , Taneja Sanjeev , Teasdale Natalie , Terpening Zoe , Van Berkel Anne , Watson John D. G. , Weiner Yolande , Wijeratne Tissa , Wilson Alison , Wolfe Nigel 
Published: January 2020

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:
ACTRN
12613000939796 and U1111‐1145‐6762