WP3c – Improving Reperfusion strategies in Ischemic Stroke (IRIS)

WP leaders

Charles Majoie (AUMC) & Yvo Roos (AUMC)

The workpackage

The RCT MR CLEAN-NO IV (CONTRAST 1.0 WP3c) studied the value of intravenous alteplase administration prior to EVT. It finished enrolment of 539 patients in 3 countries 1.5 years earlier than expected, with 0% loss-to-follow-up. The trial found comparable results with and without alteplase – but there was not enough statistical certainty to confirm non-inferiority.

Globally, five other randomized trials studied this topic: in China (DIRECT-MT, DEVT, Japan (SKIP), Switzerland (SWIFT DIRECT), Australia (DIRECT-SAFE). Only the Chinese trials found significant non-inferiority, though opinions on the used noninferiority boundaries differed. In all trials, confidence intervals were wide. The effect of alteplase differed between patient subgroups – but the trials individually had insufficient power for reliable subgroup analyses.

We propose a collaboration between all trials under the name of IRIS: Improving Reperfusion strategies in acute Ischemic Stroke. In an individual patient data meta-analysis, we can calculate the most reliable treatment effects, explore non-inferiority definitions, and perform accurate subgroup analyses. Together, we can provide the highest-level evidence for worldwide reliable guideline recommendations, and pave the way to more individualized, patient-tailored stroke care.


The key objectives of the IRIS pooling are:

  1. To provide a pooled analysis of individual patient data from 5 randomized controlled trials, to investigate whether direct EVT is non-inferior to IVT followed by EVT in patients with an ischemic stroke due to a large vessel occlusion, by prespecified non-inferiority margins.
  2. To explore whether direct EVT is non-inferior to IVT followed by EVT in prespecified subgroups.
  3. To further investigate workflow implications of the results from aims 1) and 2).
  4. To further investigate implications of imaging results from aims 1) and 2) (i.e., improving recanalization and reperfusion, thrombus imaging characteristics, etc.).
  5. To improve patient selection and to contribute towards more tailored decision-making concerning IVT use in patients requiring EVT for acute ischemic stroke.