Clinical trial NCT02712788: Milrinone in Addition to Hyperdynamic Therapy in the Treatment of Vasospasm Following Aneurysmal Subarachnoid Hemorrhage
Official title: Milrinone in Addition to Hyperdynamic Therapy in the Treatment of Vasospasm Following Aneurysmal Subarachnoid Hemorrhage
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cerebral Vasospasm
Keywords: Subarachnoid Hemorrhage
Cerebral Vasospasm
Milrinone
Hyperdynamic Therapy
Lead sponsor: Indiana University
Sponsor class: OTHER
First posted: 2016-03-18
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the usefulness of adding Milrinone to the current standard treatment for cerebral vasospasm.

Detailed description: The goal of this study is to assess the efficacy of milrinone as an agent to treat cerebral vasospasm by adding it to standard therapy. This will take the form of a randomized, controlled trial in which patients will receive either standard hyperdynamic therapy or hyperdynamic therapy + milrinone. The hypothesis of this study is that good outcomes will be 25% more common in the experimental (milrinone) group than the control (standard therapy) group.

Eligibility criteria: Inclusion Criteria:

* Subjects ≥ 18 years of age
* Aneurysmal subarachnoid hemorrhage, proven on CT angiogram or digital subtraction angiography
* Aneurysm treated, either by endovascular embolization or surgical clip ligation
* Evidence of increased velocities on transcranial dopplers (TCDs) and/or radiographic evidence of vasospasm as seen on angiogram
* Cerebral vasospasm as demonstrated by patient's clinical exam (new focal deficit or change in mental status not attributable to any other cause)

Exclusion Criteria:

* Recurrent subarachnoid hemorrhage
* Untreated ruptured aneurysm, for any reason
* Patients who die prior to treatment for aneurysm
* Patients who are not able to complete at least 6 months of follow-up
* Patients who are admitted already in vasospasm (i.e. a delayed admission)
* Creatinine clearance less than 20 ml/min
* Women with a positive pregnancy test or who are lactating
* Other comorbidity which may adversely affect patient outcome, at the discretion of the principal investigator

Primary outcomes:
measure: Modified Rankin Scale (mRS) at 6 Months
timeFrame: 6 months
Secondary outcomes:
measure: mRS at 12 Months
timeFrame: 12 months
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University Heath Methodist Hospital
state: Indiana
Study officials:
affiliation: Indiana University
name: Scott Shapiro, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Abla AA, Wilson DA, Williamson RW, Nakaji P, McDougall CG, Zabramski JM, Albuquerque FC, Spetzler RF. The relationship between ruptured aneurysm location, subarachnoid hemorrhage clot thickness, and incidence of radiographic or symptomatic vasospasm in patients enrolled in a prospective randomized controlled trial. J Neurosurg. 2014 Feb;120(2):391-7. doi: 10.3171/2013.10.JNS13419. Epub 2013 Dec 6.
citation: Diringer MN, Bleck TP, Claude Hemphill J 3rd, Menon D, Shutter L, Vespa P, Bruder N, Connolly ES Jr, Citerio G, Gress D, Hanggi D, Hoh BL, Lanzino G, Le Roux P, Rabinstein A, Schmutzhard E, Stocchetti N, Suarez JI, Treggiari M, Tseng MY, Vergouwen MD, Wolf S, Zipfel G; Neurocritical Care Society. Critical care management of patients following aneurysmal subarachnoid hemorrhage: recommendations from the Neurocritical Care Society's Multidisciplinary Consensus Conference. Neurocrit Care. 2011 Sep;15(2):211-40. doi: 10.1007/s12028-011-9605-9.
citation: Fraticelli AT, Cholley BP, Losser MR, Saint Maurice JP, Payen D. Milrinone for the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Stroke. 2008 Mar;39(3):893-8. doi: 10.1161/STROKEAHA.107.492447. Epub 2008 Jan 31.
citation: Lannes M, Teitelbaum J, del Pilar Cortes M, Cardoso M, Angle M. Milrinone and homeostasis to treat cerebral vasospasm associated with subarachnoid hemorrhage: the Montreal Neurological Hospital protocol. Neurocrit Care. 2012 Jun;16(3):354-62. doi: 10.1007/s12028-012-9701-5.
citation: Nishiguchi M, Ono S, Iseda K, Manabe H, Hishikawa T, Date I. Effect of vasodilation by milrinone, a phosphodiesterase III inhibitor, on vasospastic arteries after a subarachnoid hemorrhage in vitro and in vivo: effectiveness of cisternal injection of milrinone. Neurosurgery. 2010 Jan;66(1):158-64; discussion 164. doi: 10.1227/01.NEU.0000363153.62579.FF.