Milrinone in Addition to Hyperdynamic Therapy in the Treatment of Vasospasm Following Aneurysmal Subarachnoid Hemorrhage

Phase 2

Terminated

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo (Normal Saline) will be administered intravenously and titrated based on symptoms in addition to hyperdynamic therapy and angiographic therapy as indicated per institutional protocol.
Milrinone	Milrinone	Milrinone will be administered intravenously at an initial rate of 0.75mCg/kg/min and titrated based on symptoms in addition to hyperdynamic therapy and angiographic therapy as indicated per institutional protocol.

Primary Outcome Measures

Name	Time	Method
Modified Rankin Scale (mRS) at 6 Months	6 months	Reported as number for each subject and then will look statistically to see if there is a difference between the active arm and the placebo arm. The Modified Rankin scale is Scored as follows: 0 = No symptoms, 1 = No significant disability. Able to carry out all usual activities, despite some symptoms, 2 = Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities, 3 = Moderate disability. Requires some help, but able to walk unassisted, 4 = Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted, 5 = Severe disability. Requires constant nursing care and attention, bedridden, incontinent, 6 = Death. Higher scores indicate worse outcome.

Secondary Outcome Measures

Name	Time	Method
mRS at 12 Months	12 months	Reported as number for each subject and then will look statistically to see if there is a difference between the active arm and the placebo arm. THe Modified Rankin Scale is Scored as follows: 0 = No symptoms, 1 = No significant disability. Able to carry out all usual activities, despite some symptoms, 2 = Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities, 3 = Moderate disability. Requires some help, but able to walk unassisted, 4 = Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted, 5 = Severe disability. Requires constant nursing care and attention, bedridden, incontinent, 6 = Death. Higher scores indicate worse outcome.