Clinical trial NCT01569100: Atorvastatin After Aneurysmal Subarachnoid Hemorrhage
Official title: Atorvastatin Effect in Incidence and Ischemic Complications of Vasospasm After Subarachnoid Aneurysmal Hemorrhage: a Cohort Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: SAH
Lead sponsor: Groupe Hospitalier Pitie-Salpetriere
Sponsor class: OTHER
First posted: 2012-04-02
Enrollment: 278
Sex: ALL
Minimum age (years): 16
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients admitted between April 20, 2004, and October 1, 2007, to the Pitie- Salpetriere Teaching Hospital in Paris with aneurysmal SAH and treated by endovascular coiling or surgery within 96 hrs after SAH onset were considered for inclusion.

Brief summary: The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, known as statins, have recently been demonstrated to improve endothelial function. Additionally, numerous studies have shown statins as having antiinflammatory and cell-signaling effects together with a selective up-regulation of the eNOS activity. These findings are of potential benefit for the prevention of cerebral vasospasm after a aneurysmal subarachnoid hemorrhage. Indeed, one of the possible mechanisms for this vasospasm is the eNOS depletion or even increase of eNOS expression after the hemorrhage. The purpose of this study is to observe the immediate effect of statins after aneurysmal subarachnoid hemorrhage (aSAH) in cerebral vasospasm and outcome at one year.

Detailed description: Up to now, the preventive and curative treatment of vasospasm secondary to subarachnoid aneurismal hemorrhage has been based on three major approaches: increasing arterial pressure and cerebral blood flow with the use of triple H therapy, increasing the ischemic threshold of neurons with nimodipine and reopening proximal arteries with angioplasty and/or intra-arterial administration of nimodipine, verapamil, milrinone or papaverine. Recently, several teams have observed the efficacy of diverse statins in the prevention of vasospasm by improving the imbalance between the nitric oxide and the endothelin pathways, a major actor in the physiopathology of vasospasm. Indeed, this family of molecules improve the bioavailability of endogenous nitric oxide and upregulate the endothelial NO synthase.

In humans, statin administered within the first 72 hours showed to significantly reduce the incidence of vasospasm up to 50% an therefore, induce a lower morbidity and mortality of this severely ill population. The aim of this study is to demonstrate that atorvastatin reduces the incidence of cerebral vasospasm-related morbidity and mortality within 1 year post aneurysmal subarachnoid hemorrhage (aSAH) treated by either clipping or endovascular coiling.

Eligibility criteria: Inclusion Criteria:

* SAH patient \> 16 years-old admitted to the Pitie- Salpetriere Teaching Hospital
* Securing procedure within 96 hours of bleeding

Exclusion Criteria:

* Securing procedure \> 96 hours of bleeding
* Rebleeding of original aneurysm

Primary outcomes:
measure: S100B assay measured daily from days 1-15
timeFrame: Day 1 through 15
Secondary outcomes:
measure: Ischemic lesion volume
timeFrame: admission upon death or hospital discharge
Other outcomes:
Locations:
Study officials:
affiliation: Departments of Anesthesiology and Critical Care, Pitie-Salpetriere Hospital, APHP, University Pierre et Marie Curie, Paris, France
name: Louis Puybasset, Pr
role: PRINCIPAL_INVESTIGATOR
References: