Intraventricular extension of hemorrhage (IVH) is a particularly poor prognostic sign, with
expected mortality between 50% and 80%. IVH is a significant and independent contributor to
morbidity and mortality, yet therapy directed at ameliorating intraventricular clot has been
limited. Conventional therapy centers on managing hypertension and intracranial pressure
while correcting coagulopathy and avoiding complications such as rebleeding and
hydrocephalus. Surgical therapy alone has not changed the natural history of the disease
significantly. Although ventriculostomy appears to be effective in controlling ICP, this
technique does little to reduce morbidity and does not address the inflammatory process. The
severity of communicating hydrocephalus appears to be related to IVH volume and the duration
of exposure of CSF to clotted blood.
Management of hemorrhagic patients is typically orchestrated by neurosurgeons and
neuro-intensivists. Comprehensive care should include surveillance and monitoring of
intracranial pressure (ICP), Cerebral Perfusion Pressure (CPP), and hemodynamic function.
Furthermore, prevention of infection, complications of immobility through positioning and
mobilization within physiological tolerance play an important role in optimizing outcomes
after intracerebral hemorrhage (ICH).
There are multiple approaches to facilitating Cerebrospinal Fluid (CSF) drainage and
intracranial pressure (ICP) monitoring. Routinely, ICP is measured by use of devices inserted
into the brain parenchyma or cerebral ventricles. A Ventricular Catheter (VC) inserted into
the lateral ventricle allows for drainage of CSF to help reduce ICP.
The IRRAflow system performs active, controlled fluid exchange, based on the notion that it
is faster to wash out IVH, compared to gravity drainage alone. IRRAflow combines periodic,
controlled irrigation and aspiration of the catheter probe with neutral physiological fluids.
The continuous perfusion cleans the entire inner catheter probe's surface while the fluid
movement helps to disrupt potential clot or bacteria colony formation on the catheter probe's
intracranial external surface, thereby eliminating the underlying reasons for the problems
associated with passive drainage: blockage and infection. Furthermore, IRRAflow perfusion is
combined with continuous ICP monitoring that includes safety alarms. Contrary, with passive
drainage, such as today's standard of care, the external ventricular drain (EVD), is
inherently inefficient because of its inability to overcome blood clot adhesion. As a result,
EVD's generally need a lot of treatment time for the evacuation of a clinically significant
blood volume and often leave enough volume of residual blood to create secondary adverse
effects, like hydrocephalus. IRRAflow was designed to increase drainage efficiency by means
of gradual and continuous dilution of the pathological intracranial fluids through irrigating
the catheter with physiological fluids as well as the continuous pressure fluctuations inside
the pathological collection, which are created by the appropriate irrigation patterns. By
design, the IRRAflow catheter probe is irrigated regularly in a way that maintains its
patency. Catheter blockages are theoretically very unlikely since any material build-up at
the catheter's tip is washed away during the next irrigation phase, which will occur in, at
most, a couple of minutes. Additionally, the volume and flow rate of each irrigation is such
that the length of the IRRAflow catheter probe's outer surface is washed by backflow, thus
arguably reducing the chance for bacterial colonisation (Data on File at IRRAS). As for
safety, IRRAflow automatically, reliably, and continuously monitors ICP and alerts hospital
personnel with visual and sound alarms immediately when the patient's ICP is out of the
pressure range set by the treating neurosurgeon, which eliminates any delay in detecting
under or over drainage and any treatment's compromise.
The clinical efficacy of the IRRAflow system is currently validated to a limited extent based
on case series (Evidence grade 4) with a total number of patients around 200 distributed
across multiple countries including in Greece, India, Sweden, Germany, UK, USA, and Finland.
The system has been used to treat subarachnoid, intraventricular, intraparenchymal, and
subdural hemorrhages. The system was CE Marked in 2014 and began limited market release in
Germany in 2017. It received US FDA clearance in July of 2018 and began to be used
commercially based on the conclusion that the device was safe. Case report data on the 200
initial patients has been collected by the company and maintained on file. The data has shown
that zero IRRAflow catheter occlusions have been experienced when the irrigation setting has
been activated (unpublished). Furthermore, treatment times were much shorter and
posttreatment residual blood volumes were less than expected by the treating neurosurgeons
(31), (Data on File at IRRAS). To date there have not been any documented blockages or probe
associated infections detected in any IRRAflow treatment.
At present time, there is no level 1 evidence for treatment efficacy. However, the treatment
is new and intuitively rational, and it is applied for patients with intraventricular
hemorrhage, which has an extremely high mortality and morbidity rate, for whom there are no
other treatment options.
In light of the above, the current clinical ACTIVE study is being initiated to evaluate the
hypothesis that active irrigation by IRRAflow® will reduce the time needed for clearance of
intraventricular blood from intraventricular space compared with passive drainage. Further,
active controlled irrigation can improve catheter occlusion and infection rates compared with
passive drainage. This is accomplished through IRRAflow's mechanism of action, Active Fluid
Exchange (continuous, intelligent irrigation combined with continuous drainage and ICP
monitoring). This active fluid exchange could enable an optimal washout of the ventricles
thus leading to better outcomes than traditional treatment. Clinical evidence supporting this
hypothesis has already been established by Zhang et al., 2007, and the aforementioned
article. The investigators aim to provide that similar results can be obtain through less
invasive methods.
The investigators expect that the ACTIVE study will provide the first grade 1 evidence to
date characterizing the IRRAflow IVH clearance performance, documenting device safety, and
additionally provide preliminary indications of the potential correlated improvements in
clinical outcome and cost-effectiveness of treatment as well as a potential reduction in
post-surgical complications such as post-ictus hydrocephalus and central nervous system (CNS)
infection. Endpoints and objectives are elaborated further below. If positive, the Study will
provide a pivotal argument for the use of active fluid exchange in the treatment of
hemorrhagic stroke with ventricular involvement, potentially changing standard practice for
the better
The proposed study is a multi center prospective, controlled, randomized trial to evaluate
the efficacy and safety of evacuation of intraventricular hematoma by Active external
ventricular drainage (INTERVENTION - IRRAflow) compared to passive external ventricular
drainage (CONTROL - EVD).
Randomization of the study will occur following enrollment upon the patient presentation to
the emergency room. Upon initial diagnosis and enrollment, if it is determined that a CSF
drainage is necessary, the patient will be randomized to either the IRRAflow with Active
Fluid Exchange arm (intervention) or a standard practice EVD arm (control). The randomization
will occur in a 1 to 1 fashion. This means, that 50% of cases will be randomized to the
intervention and 50% to control. Drainage therapy with EVD or IRRAflow will commence for as
long as it is deemed necessary by the treating physician. All patients enrolled in the trial
will receive additional supportive and medical treatment by choice of the treating physician
and in accordance with standard of care. Such treatment may include neurointensive care,
neuromonitoring, and surgical or endovascular occlusion identified sources of intracranial
hemorrhage, e.g. vascular anomalies, aneurisms, etc. Interventional treatment will be stopped
in case of 1) patient exclusion from the trial, 2) ethical or medical safety
contraindications for further interventional treatment determined by the Investigators.
