Cerebral Vasospasm
Conditions
Keywords
Subarachnoid Hemorrhage, Cerebral Vasospasm, Milrinone, Hyperdynamic Therapy
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.
Interventions
DRUGMilrinone
DRUGPlacebo
Sponsors
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Milrinone | 2 |
| 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.
Placebo | 2 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Milrinone | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 2 Participants | 4 Participants |
| Region of Enrollment United States | 2 participants | 2 participants | 4 participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 1 / 2 | 1 / 2 |
| serious Total, serious adverse events | 1 / 2 | 1 / 2 |
Outcome results
Primary
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.
Time frame: 6 months
Population: The 2 subjects in the milrinone arm were unable to be analyzed. 1 subject was withdrawn due to ineligibilty and the other was withdrawn per physician discretion.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Modified Rankin Scale (mRS) at 6 Months | 1.5 score on a scale |
Secondary
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.
Time frame: 12 months
Population: The 2 subjects in the milrinone arm were unable to be analyzed. 1 was withdrawn due to ineligibility and the other was withdrawn due to physician discretion.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | mRS at 12 Months | 2 score on a scale |