Metoprolol for Subarachnoid Hemorrhage

(BADCATS Trial)

Overseen By Madeleine Puissant, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Madeleine Puissant

Disqualifiers: Pregnancy, Severe heart failure, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how metoprolol can aid individuals who have experienced a non-traumatic subarachnoid hemorrhage, a type of brain bleeding not caused by injury. Researchers aim to determine if early administration of metoprolol can enhance recovery. Participants will receive either metoprolol or a placebo (a pill with no active medicine) during the first three days in the hospital. Individuals with this specific type of brain bleed, confirmed by imaging, may be suitable candidates. As a Phase 4 trial, metoprolol is already FDA-approved and proven effective, and this research seeks to understand its benefits for more patients.

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 is the safety track record for Metoprolol?

Research shows that metoprolol is usually well-tolerated. Studies have found that it can lower the risk of death by 34% in certain heart conditions compared to a placebo over a year. It is often used to treat heart issues and lower blood pressure, with its safety for these purposes well-established.

Researchers have also studied metoprolol in people with vasovagal syncope, a condition that causes fainting. It was found to be safe, although it didn't significantly reduce fainting episodes. Observational studies have not found any link between metoprolol use during pregnancy and negative effects on the baby.

Since this trial is in a later phase, researchers have tested metoprolol’s safety in many people over time. This provides strong evidence that it is generally safe for human use. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for subarachnoid hemorrhage (SAH) focus on managing symptoms and preventing complications, often using calcium channel blockers like nimodipine. But metoprolol works differently, targeting the beta-adrenergic receptors to help stabilize heart rate and blood pressure. Researchers are excited about metoprolol because it may offer a new way to protect the brain by potentially reducing secondary brain injury in the critical initial hours after a hemorrhage. Unlike standard treatments, which take time to show effectiveness, metoprolol could provide rapid benefits within the first 72 hours of hospitalization.

What is the effectiveness track record for metoprolol in treating subarachnoid hemorrhage?

In this trial, participants will receive either metoprolol or a placebo during the first 72 hours of hospitalization after non-traumatic subarachnoid hemorrhage (SAH). Research has shown that metoprolol, a beta-blocker, can stabilize heart rate and blood pressure in patients with SAH, a type of brain bleeding. Studies have also found that metoprolol succinate can reduce the risk of death by 34% compared to a placebo over a year. This suggests that metoprolol might improve outcomes for these patients by managing vital body functions. Beta-blockers like metoprolol block the effects of adrenaline, helping to maintain a steady heart rate and lower blood pressure. ^{1 4 6 7 8}

Who Is on the Research Team?

Madeleine Puissant, MD, PhD

Principal Investigator

MaineHealth

Are You a Good Fit for This Trial?

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

Pregnancy

Patient or legally authorized representative unwilling to provide informed consent

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Metoprolol

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.

How Is the Trial Designed?

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 United States, European Union, Canada for the following indications:

Approved in United States as Lopressor, Toprol XL for:

• Hypertension
• Acute Myocardial Infarction
• Congestive Heart Failure
• Angina

Approved in European Union as Lopressor, Toprol XL for:

• Hypertension
• Angina Pectoris
• Heart Failure
• Myocardial Infarction

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+

Published Research Related to This Trial

In a randomized, placebo-controlled trial involving 208 patients with vasovagal syncope, metoprolol did not significantly reduce the risk of recurrent syncope compared to placebo over a 1-year treatment period.

The study found that neither the age of the patients nor their initial tilt-test results predicted any benefit from metoprolol, indicating that this beta-blocker is not effective for preventing vasovagal syncope.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of Syncope Trial (POST): a randomized, placebo-controlled study of metoprolol in the prevention of vasovagal syncope. Sheldon, R., Connolly, S., Rose, S., et al.[2022]

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]

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 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, particularly in its controlled release (CR/XL) form, has been shown to significantly lower mortality rates in patients with chronic heart failure compared to other forms, such as immediate release (IR) and sustained release (SR).

While metoprolol SR does not demonstrate superior antihypertensive efficacy compared to IR or CR/XL, the new controlled release formulation (CD/ERT) has been proven bioequivalent to CR/XL, suggesting it may offer similar benefits in managing heart conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evolution of oral drug forms of metoprolol: advantages of long acting modified release forms with modified release]. Leonova, MV., Maneshina, OA., Belousov, IuB.[2017]

The ongoing UNAMET study is evaluating the impact of metoprolol on quality of life and the incidence of adverse drug reactions (ADRs) in outpatients, using standard questionnaires over a 6-week period.

The study aims to determine if genotyping for the CYP2D6 enzyme can help guide initial dosing of metoprolol, particularly for patients who are poor metabolizers and may be at higher risk for ADRs.

NCBI (Pubmed)

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]. Fux, R., Meisner, C., Schwab, M., et al.[2015]

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]

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]

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]

Citations

1. withpower.com withpower.com/trial/phase-4-non-traumatic-subarachnoid-hemorrhage-8-2024-97a2a

Metoprolol for Subarachnoid Hemorrhage (BADCATS Trial) Research shows that Metoprolol, a type of beta-blocker, can help stabilize heart rate and blood pressure in patients with subarachnoid hemorrhage, reducing the ...

2. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK532923/

Metoprolol - StatPearls - NCBI Bookshelf [4] The results showed that metoprolol succinate reduced the risk of death by 34% compared with placebo over a mean follow-up of 1 year.

3. researchgate.net researchgate.net/publication/353493601_Effectiveness_comparisons_of_drug_therapies_for_postoperative_aneurysmal_subarachnoid_hemorrhage_patients_network_meta-analysis_and_systematic_review

(PDF) Effectiveness comparisons of drug therapies for ... Conclusions Both nimodipine and cilostazol have exact curative effect to improve the outcome of postoperative patients with aSAH, and cilostazol ...

4. bmcneurol.biomedcentral.com bmcneurol.biomedcentral.com/articles/10.1186/s12883-021-02303-8

Effectiveness comparisons of drug therapies for postoperative ... Efficacy and safety of fasudil in patients with subarachnoid hemorrhage: final results of a randomized trial of fasudil versus nimodipine.

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/019962s049lbl.pdf

This label may not be the latest approved by FDA. For current ... Metoprolol succinate was also shown to delay the increase in left ventricular end-systolic and end-diastolic volumes after 6 months of treatment.

6. rxlist.com rxlist.com/toprol-xl-drug.htm

Toprol XL (Metoprolol Succinate): Side Effects, Uses, ... Risk Summary. Untreated hypertension and heart failure during pregnancy can lead to adverse outcomes for the mother and the fetus (see Clinical Considerations).

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2025/219373s000lbl.pdf

LOPRESSOR® (metoprolol tartrate) oral solution Available data from published observational studies have not demonstrated an association of adverse developmental outcomes with maternal use of metoprolol ...

8. webmd.com webmd.com/drugs/2/drug-8814-2372/metoprolol-succinate-oral/metoprolol-succinate-extended-release-capsule-oral/details

Metoprolol (Lopressor, Toprol XL, others) - Uses, Side ... These effects can help your heart work better, lower blood pressure, and may reduce your risk for heart attack and stroke.