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

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

Detailed Description
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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.

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

Conditions
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Cerebral Vasospasm

Intervention / Treatment
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* Drug: Milrinone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Milrinone<br>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. | Drug: Milrinone<br> <br> |
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Rankin Scale (mRS) at 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. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mRS at 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. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Subarachnoid Hemorrhage, Cerebral Vasospasm, Milrinone, Hyperdynamic Therapy