Study protocol for ACTIVE study: safety and feasibility evaluation of external ventricular drainage with ACTIVE fluid exchange in intraventricular hemorrhage-a phase 2, multi-center, randomized controlled trial.

ABSTRACT

BACKGROUND: Primary intraventricular hemorrhage (IVH) or IVH secondary to intracerebral (ICH) and subarachnoid hemorrhage (SAH) are known to have a very poor prognosis, with an expected mortality between 50 and 80% (Hinson et al. Current Neurology and Neuroscience Reports 1073-82, 2010). Clearance of IVH might improve patient outcome. METHODS: The study is designed as an investigator-initiated, comparative, prospective, multi-center, 11 randomized phase 2 trial evaluating the efficacy and safety of active irrigation in external ventricular drainage (intervention arm-IRRAflow) compared to passive external ventricular drainage (control arm-EVD). The trial will enroll 58 patients with primary or secondary IVH. Major eligibility criteria include age ≥18 years of age, IVH documented on head CT or MRI scan (Graeb score ≥3), need of cerebrospinal fluid drainage, deterioration of consciousness or medical sedation at the time of enrollment, and indication for active treatment evaluated by the treating physicians. Exclusion criteria included patients with fixed and dilated pupils and pregnant or nursing women. The primary endpoint of the study is catheter occlusion evaluated by time to first observed occlusion from VC placement. Secondary endpoints include clearance of ventricular blood as measured by head CT scan, rates of catheter-related infection and shunt dependency, length of intensive care unit stay, functional status-Extended Glascow Outcome Scale (eGOS) and modified Rankin scale (mRS) at discharge to rehabilitation and 90 days-and mortality rates at 30 days and 90 days. DISCUSSION: With no standardized treatment for IVH and a poor prognosis, new treatments are needed. IVH patients often need CSF drainage to treat hydrocephalus and to decrease ICP. Standard treatment with passive external ventricular drainage is related to an increased risk of infections which is found in up to 22% of treated cases. The passive VC is known to have a risk of occlusion and is seen in 19-47% of the cases. We hypothesize that the use of active fluid change using the IRRAflow system will be safe and feasible and will reduce the occlusion and infection rates in patients with IVH. TRIAL REGISTRATION ClicalTrials.gov NCT05204849. Registered 15 December 2021. Updated 24 January 2022.