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: ACTRN 12613000939796 and U1111‐1145‐6762

Process evaluation of an implementation trial to improve the triage, treatment and transfer of stroke patients in emergency departments (T3 trial): a qualitative study

“…These findings fill an important gap in the literature by providing insights into the challenges involved with implementing new and complex interventions for time-critical conditions such as stroke in the ED. The ED is a setting for which there is limited evidence for successful stroke care intervention uptake [ 21 ].…”

Thrombolysis implementation intervention and clinical outcome: a secondary analysis of a cluster randomized trial

“…Although the TIPS trial did observe a significant but transient increase in thrombolysis rates (OR = 1•6; 95% CI; 1•1-2•3) during the initial 16-month active intervention period [7], this posthoc analysis at the individual patient level, found that the intervention promoting thrombolysis implementation did not result in any significant difference in excellent or poor outcome between patients treated at intervention versus control hospitals. A non-significant decrease in the rate of hemorrhages following intravenous thrombolysis was seen during both active and post-intervention period.…”

“…The trial resulted in a transient uplift in intravenous thrombolysis rates in the intervention hospitals. However, the primary outcome of the trial was an overall non-significant increase in thrombolysis rates in the intervention versus control sites which was not sustained beyond the 16-month intervention period [7]. As described in the main trial outcome paper [7], there were challenges with intervention implementation at some regional hospitals, and the uptake of "best practice" knowledge translation strategies was limited by clinical leadership availability and staffing constraints [8].…”

“…However, the primary outcome of the trial was an overall non-significant increase in thrombolysis rates in the intervention versus control sites which was not sustained beyond the 16-month intervention period [7]. As described in the main trial outcome paper [7], there were challenges with intervention implementation at some regional hospitals, and the uptake of "best practice" knowledge translation strategies was limited by clinical leadership availability and staffing constraints [8]. However, despite the non-significant change in overall thrombolysis rates seen in the trial, it was considered possible that the TIPS intervention may have had a positive effect on individual patient clinical outcomes, for example, influencing improved selection of cases for thrombolysis treatment and streamlining of workflows [9].…”

Door to needle time for thrombolysis: A secondary analysis of the TIPS cluster randomized controlled trial

“…This intervention was based on the behaviour change wheel 14 . The study achieved significant improvement of intravenous thrombolysis rates in the intervention hospitals during the active intervention phase, however, this improvement was no longer significant during the post-intervention phase 15 . In this study, we will explore the effect of the TIPS intervention on DTN, as well as door-to-imaging (DTI), and imaging-to-needle (ITN) times.…”