IMPROVING OUTCOME IN SUBARACHNOID HEMORRHAGE WITH NADROPARINE

Mortality and morbidity after aSAH is high and are, for a large part, caused by
delayed cerebral ischemia (DCI). For long, DCI after aneurysmal subarachnoid
hemorrhage (aSAH) was thought to be caused by vasospasm, induced by blood in
the subarachnoïd space. Growing experimental and clinical evidence now suggest
activation of several (intravascular) pathophysiological pathways, affecting
the cerebral microcirculation. Recently, in a retrospective analysis of our
Academic Medical Center (AMC) aSAH patient registry, we observed lower
in-hospital mortality and less non-home discharge in patients treated with
therapeutic low-molecular weight heparin (LMWH), compared to patients treated
with standard, prophylactic LMWH. This points towards a potential benefit of
higher doses of LMWH in the acute course after an aSAH. We therefore
hypothesize that treatment with therapeutic LMWH will improve clinical outcome
in endovascularly treated aSAH patients.

This study has been transitioned to CTIS with ID 2024-511679-14-00 check the CTIS register for the current data.

Our primary objective is to evaluate whether aSAH patients treated with
therapeutic dose nadroparine have a lower 30-days mortality rate compared to
aSAH patients treated with prophylactic dose nadroparine.

A single-center, prospective, phase II randomized clinical trial.

Therapeutic dose of nadroparine (5700IE twice daily), continued until 21 days
after initial SAH or untill discharge, compared to a standard profylactic dose
(2850IE once daily).

An aneurysmal subarachnoid hemorrhage is a life-threatening form of stroke.
Mortality in aSAH amounts to 32%-39% and 50% of the survivors experience a
permanent disability, in which DCI is a leading cause. In a recent
retrospective analysis of the same cohort of patients, a benefit has been shown
for treatment with therapeutic dosages of LMWH compared to standard
prophylactic dosages. The biggest risk related to LMWH is the theoretically
higher chance of hemorrhages; spontaneous and after surgery. In contrast, there
was no increase in (hemorrhagic) complications in patients treated with a
therapeutic dose of LMWH, investigated in a retrospectively cohort in our own
centre. The expected benefit is large, as half of the patients is younger than
55-years-old. Reduction in death or disability, leading to improved clinical
outcome, could significantly decrease the loss of productive life years, with
enormous economic and social impact.