Beta-1 Adrenergic Inhibition to Reduce Cardiac Injury and Inflammation After Subarachnoid Hemorrhage (BADCATS) (BADCATS)

To determine the effect of early metoprolol administration after non-traumatic subarachnoid hemorrhage (SAH).

Study Overview

• Status: Recruiting
• Conditions: Non-Traumatic Subarachnoid Hemorrhage
• Intervention / Treatment: Drug: Metoprolol; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Madeleine Puissant, MD, PhD; Phone Number: 2076613660; Email: Madeleine.Puissant@mainehealth.org
• Study Contact Backup: Name: Christine Lord; Email: Christine.Lord@mainehealth.org

Study Locations

• United States
  • Maine
    • Portland, Maine, United States, 04012
      • Recruiting
      • MaineHealth
      • Contact: Christine Lord; Phone Number: 2076613660; Email: christine.lord@mainehealth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metoprolol (Beta-adrenergic blockade); Patients will receive metoprolol during the first 72-hours of hospitalization after non-traumatic SAH.	Drug: Metoprolol; 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; Other Names: Metoprolol succinate
Placebo Comparator: Placebo; Patients will receive placebo during the first 72-hours of hospitalization after non-traumatic SAH.	Drug: Placebo; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delta QTc length	Change (Delta) QTc length between intervention and control groups.	7 days
Delta neutrophil activity	Delta neutrophil activity between intervention and control groups.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Including but not limited to symptomatic bradycardia, symptomatic hypotension, or complete heart block	7-days
Number of patients with evidence of cardiac injury	Measurement of troponin levels, echocardiograph	7-days
Need for Vasopressors	Any documented intravenous vasoactive medication administration	7-days
Sympathetic Nervous System (SNS) Activity	Catecholamine Measurements	7-days
Neutrophil Activity	Measurement of neutrophils in CSF and serum samples	7 days
Evidence of Clinical Vasospasm	Evidence of clinical vasospasm	Up to 15-weeks
ICU Length of Stay (LOS)	Number of full days	Up to 15-weeks
Hospital Length of Stay (LOS)	Number of full days	Up to 15-weeks
In-hospital mortality	Whether patient died during during sentinel hospitalization	Up to 15-weeks

Collaborators and Investigators

• Sponsor: Madeleine Puissant
• Collaborators: MaineHealth
• Investigators: Principal Investigator: Madeleine Puissant, MD, PhD, MaineHealth

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: August 19, 2024
• First Submitted That Met QC Criteria: August 22, 2024
• First Posted (Actual): August 23, 2024

Study Record Updates

• Last Update Posted (Estimated): November 26, 2024
• Last Update Submitted That Met QC Criteria: November 22, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Inflammation; Cardiac dysfunction; Beta-adrenergic blockade
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Intracranial Hemorrhages; Inflammation; Hemorrhage; Subarachnoid Hemorrhage; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Anti-Arrhythmia Agents; Adrenergic Agents; Antihypertensive Agents; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-Antagonists; Adrenergic Antagonists; Metoprolol
• Other Study ID Numbers: 2146714

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data will be shared.
• IPD Sharing Time Frame: At study completion and until 6-months post-publication.
• IPD Sharing Access Criteria: A de-identified data set will be made available and people may request access to this.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No