Non-Traumatic Subarachnoid Hemorrhage
Conditions
Keywords
Beta-adrenergic blockade, Cardiac dysfunction, Inflammation
Brief summary
To determine the effect of early metoprolol administration after non-traumatic subarachnoid hemorrhage (SAH).
Detailed description
To determine the effect of early metoprolol administration after non-traumatic subarachnoid hemorrhage (SAH) on the brain and cardiac tissue damage and inflammation, we will conduct a pilot randomized controlled trial comparing (1) sympathetic nervous system (SNS) activation, (2) cardiac rhythm abnormalities, (3) biomarkers of brain and cardiac tissue damage, and (4) and neutrophil activity in patients receiving metoprolol (n=10) or placebo (n=10) for the first 72-hours after SAH.
Interventions
DRUGMetoprolol
Metoprolol Dosing: Metoprolol Injection (instructions: 5mg, once) Metoprolol Tab (25mg PO, q12 hours, timed to start 1hr after Metoprolol Injection, 6 doses) If unable to take PO medication, Metoprolol Injection (instructions, 5mg q6hrs for 12 doses) Continue for 72-hours of administration unless reaching stopping criteria
DRUGPlacebo
Placebo Dosing: Placebo Injection (instructions: 5mL NS, once) Placebo Tab (1 tab PO, q12 hours, timed to start 1hr after placebo injection, 6 doses) If unable to take PO medication, Placebo Injection (instructions, 5mL q6hrs for 12 doses) Continue for 72-hours of administration unless reaching stopping criteria
Sponsors
MaineHealth
Madeleine Puissant
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* \>18 years of age * Neuro-imaging confirmed non-traumatic subarachnoid hemorrhage
Exclusion criteria
* Traumatic cause of subarachnoid hemorrhage (e.g. fall, motor vehicle accident, other blunt trauma) as this is a different mechanism of hemorrhage. * Other forms of traumatic or non-traumatic intracranial bleed including intracerebral hemorrhage (ICH), subdural hemorrhage, epidural hemorrhage * Pregnancy (as the study medication, metoprolol, has FDA Pregnancy Category C rating) * Unstable vital signs not amenable to beta-1 adrenergic receptor inhibitor (B1ARi) administration including: * Systolic blood pressure \< 80 mmHg not stabilized on vasopressor medications * Heart rate \< 50 bpm associated with hypotension * Patients requiring vasopressor agents due to hypotension (SBP \<80 mmHg) * Other vital sign exclusion at the discretion of the treatment team * Previous history of severe heart failure (Stage C or D Heart Failure and/or NYHA Class III or IV) * Patient or legally authorized representative unwilling to provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Delta QTc length | 7 days | Change (Delta) QTc length between intervention and control groups. |
| Delta neutrophil activity | 7 days | Delta neutrophil activity between intervention and control groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Need for Vasopressors | 7-days | Any documented intravenous vasoactive medication administration |
| Sympathetic Nervous System (SNS) Activity | 7-days | Catecholamine Measurements |
| Neutrophil Activity | 7 days | Measurement of neutrophils in CSF and serum samples |
| Adverse events | 7-days | Including but not limited to symptomatic bradycardia, symptomatic hypotension, or complete heart block |
| ICU Length of Stay (LOS) | Up to 15-weeks | Number of full days |
| Hospital Length of Stay (LOS) | Up to 15-weeks | Number of full days |
| In-hospital mortality | Up to 15-weeks | Whether patient died during during sentinel hospitalization |
| Evidence of Clinical Vasospasm | Up to 15-weeks | Evidence of clinical vasospasm |
| Number of patients with evidence of cardiac injury | 7-days | Measurement of troponin levels, echocardiograph |
Countries
United States
Contacts
Primary ContactMadeleine Puissant, MD, PhD
Backup ContactChristine Lord
Outcome results
None listed