Safety, harm, and efficacy of IRRAflow ^® versus external ventricular drainage for intraventricular hemorrhage: A randomized clinical trial

Importance

Intraventricular hemorrhage (IVH) is associated with high morbidity and mortality. A strong need exists for treatment advances. IRRAflow ^® was recently introduced as a method for minimally invasive, controlled, and accelerated IVH wash-out. However, no current evidence supports this technology. Here, we present the first pivotal safety/efficacy evaluation in a randomized controlled setting.

Objective

To evaluate the safety and efficacy of active hematoma irrigation using the IRRAflow ^® device compared with standard external ventricular drainage (EVD) for the IVH treatment.

Design, setting, and participants

This investigator-initiated, prospective multi-center, 1:1 randomized, single-blinded, clinical trial was conducted at the Aarhus University Hospital and Odense University Hospital in Denmark from January 13, 2022 to November 24, 2022. The trial was set to include 58 IVH patients with prespecified interim analysis at final endpoint collection for the first 20 patients.

Interventions

Patients were randomized to receive either IRRAflow ^® or standard EVD treatment. The IRRAflow ^® performs periodic active irrigation and aspiration contrary to standard passive gravity-driven EVD.

Main outcomes and measures

Outcomes were chosen to reflect key IRRAflow ^® value propositions. The primary outcome was rate of catheter occlusions. The main outcome of the prespecified interim analysis was risk of severe adverse events (SAEs). Secondary outcomes were hematoma clearance rate, shunt dependency rate, procedure time for primary catheter placement, length of intensive care unit (ICU) stay, treatment duration, functional outcome (modified Rankin Scale (mRS) and extended Glasgow Outcome Scale (eGOS)) 90 days after inclusion, adverse events (AEs) (including catheter-related infections and procedure-related complications), and overall survival.

Results

The study was terminated early due to a significantly increased risk of SAEs in the IRRAflow ^® group compared with EVD (risk difference = 0.43, 95% confidence interval (CI) (0.059;0.813), p=0.044), incidence rate ratio divided by person time = 6.0, 95%CI 1.38-26.11) p=0.012).

The catheter occlusion rate was 37.5% in the IRRAflow ^® group versus 6.6% in the EVD group (p=0.141), which met the prespecified 0.2 alpha level. The median procedure time for primary catheter placement was 53.5 min compared with 12 min in the control group (p=0.0001). No significant difference was observed for other secondary outcomes. The majority of SAEs had a causal relationship with the intervention.

Conclusion and relevance

We found that the current IRRAflow ^® treatment is encumbered by a significantly increased number of SAEs. We recommend caution when using the device. Based on root-cause analysis, our recommendation is that a number of changes be implemented to improve the safety of the device in IVH treatment. We believe that our results are pivotal in ensuring the future safety of patients with IVH.

Trial registration

<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://ClicalTrials.gov">ClicalTrials.gov</ext-link> identifier: <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT05204849">NCT05204849</ext-link> , registered 15 December 2021, updated 24 December 2022.