Efficacy of rFVIIa (NiaStase RT ®) on haematoma growth reduction and clinical evolution in patients with intracerebral haemorrhage with non-contrast CT radio- markers of haemorrhage expansion: a randomized, controlled, double-blind trial

Abstract

Background Haematoma expansion has been associated with early neurological deterioration, mortality and worse functional outcome in patients with intracerebral haemorrhage (ICH). rFVIIa (NiaStase RT®) has shown promising results in avoiding early haematoma growth, but previous studies have been done in all patients regardless of their risk for haematoma expansion. Some studies have isolated patients with high risk for haematoma expansion (SPOTLIGHT), but they used CT angiography (CTA) techniques (not available in all hospitals) and had long therapeutic windows. Therefore, evidence of the drug’s effectiveness up until now has been unclear. Some non-contrast computerized tomography (NCCT) characteristics of ICH have been associated with this early haematoma expansion. These radio-markers could be used in all hospitals with available CT, and might guarantee a correct therapeutic window for the drug. Purpose The aim of this study is to evaluate the effect of rFVIIa (NiaStase RT®) on patients with high risk of haematoma growth evaluated with NCCT radio-markers. We will assess its effects on mortality and morbidity on the patients it is given to.

Design Multicentre, double blind, placebo-controlled randomized clinical trial in the tertiary centres of the

Institut Català de la Salut (ICS).

Population Patients admitted to tertiary centres within the Institut Català de la Salut (ICS) with the diagnosis of acute primary spontaneous ICH (nontraumatic and non-anticoagulant-related ICH), with NCCT radio-markers of haemorrhage growth. A non-probabilistic consecutive sampling will be performed expecting to gather a minimum sample of 148 patients. These patients will be randomized in two groups, one for intervention (NiaStase RT®) and the other for control.

Methods The patients will be administered either 80 μg/kg dose of rFVIIa (NiaStase RT®) or placebo. The CT scan will be repeated after 1 hour of drug infusion and 24 hours post dosing to assess the rate and degree of ICH growth. Likewise, neurological status measured by NIHSS and disability degree measured by mRS will be evaluated during the hospital stay and in the follow-up visits, which will be at 3 and 6 months and 1 year after the event. Mortality will be assessed for up to a year after the event