Metoprolol for Subarachnoid Hemorrhage

(BADCATS Trial)

Overseen by Madeleine Puissant, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Madeleine Puissant

Disqualifiers: Pregnancy, Severe heart failure, others

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

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

Do I need to stop my current medications for this trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team to get a clear answer.

What data supports the effectiveness of the drug Metoprolol for subarachnoid hemorrhage?

Research shows that Metoprolol, a type of beta-blocker, can help stabilize heart rate and blood pressure in patients with subarachnoid hemorrhage, reducing the need for additional blood pressure medication and improving survival rates. This suggests it may help manage the body's stress response after a brain bleed. ^{1 2 3 4 5}

Is metoprolol generally safe for humans?

Metoprolol, used for conditions like high blood pressure and heart failure, has been studied for safety and is generally well-tolerated. Common side effects can include headache, dizziness, tiredness, and sleep disturbances, but these vary depending on individual factors like genetics. ^{3 6 7 8 9}

How does the drug metoprolol differ from other treatments for subarachnoid hemorrhage?

Metoprolol is a beta-blocker that is typically used for heart-related conditions, and its use for subarachnoid hemorrhage is novel because it may help manage blood pressure and reduce stress on the heart, which is not a standard approach for this condition. ^{3 4 6 7 10}

Research Team

Madeleine Puissant, MD, PhD

Principal Investigator

MaineHealth

Eligibility Criteria

This trial is for adults over 18 who have had a non-traumatic subarachnoid hemorrhage, confirmed by neuro-imaging. It's not specified here, but typically there would be more criteria about the patient's health status and possibly other factors like how recently they've had the hemorrhage.

Inclusion Criteria

I am older than 18 years.

I have a brain bleed not caused by injury, confirmed by a scan.

Exclusion Criteria

I have had a brain bleed, such as a stroke or head injury.

My vital signs are unstable and I can't take beta-1 blockers.

Pregnancy

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants receive metoprolol or placebo during the first 72-hours of hospitalization after non-traumatic SAH

1 week

Daily monitoring during hospitalization

Follow-up

Participants are monitored for safety and effectiveness after treatment, including measurement of cardiac and brain biomarkers

7 weeks

Weekly follow-up visits

Extended Follow-up

Participants are monitored for long-term outcomes such as hospital and ICU length of stay, and in-hospital mortality

Up to 15 weeks

Treatment Details

Interventions

• Metoprolol (Beta Blocker)

Trial Overview The BADCATS trial is testing whether giving metoprolol early after a brain aneurysm that caused bleeding (subarachnoid hemorrhage) can reduce heart damage and inflammation compared to a placebo.

Participant Groups

Group I: Metoprolol (Beta-adrenergic blockade) Experimental Treatment 1 Intervention

Patients will receive metoprolol during the first 72-hours of hospitalization after non-traumatic SAH.

Group II: Placebo Placebo Group 1 Intervention

Patients will receive placebo during the first 72-hours of hospitalization after non-traumatic SAH.

Metoprolol is already approved in Canada for the following indications:

Approved in Canada as Lopressor, Toprol XL for:

• Hypertension
• Angina
• Heart Failure
• Myocardial Infarction

Who Is Running the Clinical Trial?

Madeleine Puissant

Lead Sponsor

Trials

1

Recruited

20+

MaineHealth

Collaborator

Trials

76

Recruited

43,800+

Dr. Andrew Mueller

MaineHealth

Chief Executive Officer since 2021

MD from University of North Carolina School of Medicine

Dr. Adrian Moran

MaineHealth

Chief Medical and Transformation Officer

MD from University College Dublin, Executive MBA in Healthcare from Brandeis University

Findings from Research

In patients with subarachnoid hemorrhage (SAH), lipophilic beta-blockers (propranolol, oxprenolol, metoprolol) achieve significantly higher concentrations in the brain compared to the hydrophilic beta-blocker atenolol, which may enhance their therapeutic effects.

Atenolol's low brain concentration and the resulting minimal central nervous system side effects suggest it may be safer for long-term use in SAH patients, despite its lower efficacy in the brain compared to lipophilic alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beta-blocker brain concentrations in man. Cruickshank, JM., Neil-Dwyer, G.[2019]

In a study of 25 patients with acute aneurysmal subarachnoid hemorrhage, treatment with the beta-blocker metoprolol significantly normalized pulse rates during the first two weeks compared to a control group, indicating its efficacy in managing autonomic disorders.

Patients receiving metoprolol did not require additional antihypertensive medication and experienced better survival rates, with no severe side effects reported, highlighting its safety and potential as a preferred treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beta-blockade in acute aneurysmal subarachnoid haemorrhage. Hamann, G., Haass, A., Schimrigk, K.[2019]

Metoprolol, a cardioselective beta blocker, offers a new treatment option for paroxysmal supraventricular tachycardia in infants and children, particularly for those who do not respond to traditional therapies like digitalis and nonselective beta blockers.

This approach may improve patient outcomes by providing a more targeted therapy that minimizes side effects associated with nonselective beta blockers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of supraventricular tachycardia with metoprolol, a cardioselective beta blocker. Hepner, SI., Davoli, E.[2017]

Metoprolol is an effective treatment for mild to moderate hypertension and angina pectoris, showing comparable efficacy to other medications like beta-blockers and diuretics, and can be administered in both twice-daily and once-daily doses.

While metoprolol has shown some benefits in reducing mortality in post-myocardial infarction patients over a longer term, its use during the acute phase of myocardial infarction remains controversial due to mixed results in mortality reduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metoprolol. An updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy, in hypertension, ischaemic heart disease and related cardiovascular disorders. Benfield, P., Clissold, SP., Brogden, RN.[2018]

In a study of 60 patients over 6 months, metoprolol succinate was found to be safe and well tolerated, with no significant differences in quality of life or withdrawal rates compared to placebo.

Patients taking metoprolol succinate experienced a significant increase in left ventricular ejection fraction and a reduction in ventricular ectopic beats, indicating improved heart function and rhythm stability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metoprolol CR/XL in patients with heart failure: A pilot study examining the tolerability, safety, and effect on left ventricular ejection fraction. Goldstein, S., Kennedy, HL., Hall, C., et al.[2019]

In a 36-month study involving patients with hypercholesterolemia, metoprolol CR/XL significantly reduced the progression of carotid intima-media thickness (IMT) compared to placebo, indicating its potential antiatherosclerotic effect when used alongside statins.

The study suggests that beta-blockers like metoprolol and statins work through different mechanisms in the atherosclerotic process, providing additive benefits for patients undergoing lipid-lowering therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of controlled release/extended release metoprolol on carotid intima-media thickness in patients with hypercholesterolemia: a 3-year randomized study. Wiklund, O., Hulthe, J., Wikstrand, J., et al.[2019]

Timolol and MK-761 effectively blocked the positive effects of isoproterenol on heart muscle contractions without reducing overall contractile force, indicating their potential as beta-adrenergic blockers.

Despite their effectiveness in isolated muscle tests, neither beta-blocker improved survival rates in hemorrhagic shock in anesthetized cats, suggesting that beta-adrenergic blockade may not be a useful treatment strategy for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Actions of non-cardiodepressant beta-adrenergic blocking agents in hemorrhagic shock. Lefer, AM., Lefer, DJ., Levin, RJ.[2014]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Beta-blocker brain concentrations in man. [2019]

2. Austria pubmed.ncbi.nlm.nih.gov

Beta-blockade in acute aneurysmal subarachnoid haemorrhage. [2019]

3. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Evolution of oral drug forms of metoprolol: advantages of long acting modified release forms with modified release]. [2017]

4. United States pubmed.ncbi.nlm.nih.gov

Successful treatment of supraventricular tachycardia with metoprolol, a cardioselective beta blocker. [2017]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Metoprolol. An updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy, in hypertension, ischaemic heart disease and related cardiovascular disorders. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Metoprolol CR/XL in patients with heart failure: A pilot study examining the tolerability, safety, and effect on left ventricular ejection fraction. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Effect of controlled release/extended release metoprolol on carotid intima-media thickness in patients with hypercholesterolemia: a 3-year randomized study. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

[Rationale and methods of the UNAMET study (dose- and CYP2D6-genotype-dependent adverse drug reactions of metoprolol)--a contribution to quality improvement in pharmacotherapy]. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

Actions of non-cardiodepressant beta-adrenergic blocking agents in hemorrhagic shock. [2014]

10. United States pubmed.ncbi.nlm.nih.gov

Prevention of Syncope Trial (POST): a randomized, placebo-controlled study of metoprolol in the prevention of vasovagal syncope. [2022]