Metoprolol for Subarachnoid Hemorrhage
(BADCATS Trial)
Recruiting in Palo Alto (17 mi)
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.12345
Is metoprolol generally safe for humans?
How does the drug metoprolol differ from other treatments for subarachnoid hemorrhage?
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
See 3 more
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 OverviewThe 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
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Metoprolol (Beta-adrenergic blockade)Experimental Treatment1 Intervention
Patients will receive metoprolol during the first 72-hours of hospitalization after non-traumatic SAH.
Group II: PlaceboPlacebo Group1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
MaineHealthPortland, ME
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Who Is Running the Clinical Trial?
Madeleine PuissantLead Sponsor
MaineHealthCollaborator
References
Beta-blocker brain concentrations in man. [2019]Patients with subarachnoid haemorrhage (SAH) have been shown to benefit from beta-blockade. SAH patients who came to surgery were investigated if they had been receiving chronic (approximately one week) oral treatment with either hydrophilic atenolol (100 mg/day) or one of the following lipophilic beta-blockers: propranolol (80 mg b.i.d.), oxprenolol (80 mg b.i.d.), or metoprolol (100 mg b.i.d.). Cerebrospinal fluid concentrations of beta-blockers did not reflect their concentrations in the brain. Brain concentrations of the three lipophilic beta-blockers were 10-20 times higher than those of atenolol. The approximate brain/plasma concentration ratios were 26 for propranolol, 50 for oxprenolol, 12 for metoprolol, and 0.2 for atenolol. The brain is thus buffered from peak blood concentrations of atenolol, and this may account for the low incidence of CNS-related side-effects with this hydrophilic beta-blocker.
Beta-blockade in acute aneurysmal subarachnoid haemorrhage. [2019]The effects of beta-blockade to prevent autonomic disorders after acute aneurysmal subarachnoid haemorrhage were prospectively investigated. 11 patients were treated with the beta-1-selective beta-blocker metoprolol (up to 200 mg/die intravenously). 14 patients received standard therapy as controls. Pulse rate, blood pressure and dosage of the additional antihypertensive medication as signs of sympathetic disturbance were registered. The main result was the normalizing of the pulse rate especially during the first two weeks in contrast to the control group. The patients in the beta-blocker group did not need further antihypertensive medication. This was mainly a result of the reduction in sympathetic activation. No severe side-effects were documented and the survival was better in the treated group. Thus, beta-blockade is able to prevent and reduce autonomic disorders, especially activation of the sympathetic tone, in subarachnoid haemorrhage. Metoprolol as a so called cardioselective beta-blocker seems to be one of the suitable agents and is considered superior to the non-selective agents.
[Evolution of oral drug forms of metoprolol: advantages of long acting modified release forms with modified release]. [2017]Review oral modified release drug forms of beta-adrenoblocker metoprolol which is used in arterial hypertension and ischemic heart disease is presented. Metoprolol has salts such as tartrate which is used for production of immediate release (IR) and sustained release (SR) forms and succinate used for production of controlled release form (CR/XL). Metoprolol SR has monolith matrix type, metoprolol CR/XL-system of multiple pellets. Effect of metoprolol tartrate (IR) on mortality was demonstrated in a number of studies in patients with arterial hypertension (AH) (MAPHY), myocardial infarction (SMT, GMT, MIAMI), dilated cardiomyopathy and heart failure (MDC). Studies of efficacy of metoprolol SR are scarce. Antihypertensive efficacy of metoprolol SR in patients with AH did not exceed that of a metoprolol IR or CR/XL. First retrospective analysis of efficacy of metoprolol tartrate and succinate (CR/XL) in patients after myocardial infarction allowed to obtain comparable results of 34% mortality lowering. In a prospective study in patients with chronic heart failure (COMET) metoprolol tartrate IR was not superior to carvedilol when mortality lowering was concerned. At the same time administration of controlled release metoprolol (CR/XL) in 2 large clinical trials (RESOLVD, MERITAHF) was advantageous in patients with chronic heart failure relative to lowering of mortality and rate of hospitalizations. A novel controlled release form of metoprolol has been created as a tartrate salt on the basis of pellet technology (CD/ERT) and its bioequivalence to metoprolol CR/XL has been proved.
Successful treatment of supraventricular tachycardia with metoprolol, a cardioselective beta blocker. [2017]Paroxysmal supraventricular tachycardia is a common problem in infancy and childhood. Past treatment has included digitalis and nonselective beta blockers (propranolol). We describe a new mode of therapy with a cardioselective beta blocker (metoprolol) that may be of use in patients resistant to standard therapy.
Metoprolol. An updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy, in hypertension, ischaemic heart disease and related cardiovascular disorders. [2018]During the intervening years since metoprolol was first reviewed in the Journal (1977), it has become widely used in the treatment of mild to moderate hypertension and angina pectoris. Although much data have accumulated, its precise mechanisms of action in these diseases remain largely uncertain. Optimum treatment of hypertension and angina pectoris with metoprolol is achieved through dose titration within the therapeutic range. It has been clearly demonstrated that metoprolol is at least as effective as other beta-blockers, diuretics and certain calcium antagonists in the majority of patients. Although a twice daily dosage regimen is normally used, satisfactory control can be maintained in many patients with single daily doses of conventional or, more frequently, slow release formulations. Addition of a diuretic may improve the overall response rate in hypertension. Several controlled trials have studied the effects of metoprolol administered during the acute phase and after myocardial infarction. In early intervention trials a reduction in total mortality was achieved in one moderately large trial of prolonged treatment, but in another, which excluded patients already being treated with beta-blockers or certain calcium antagonists and where treatment was only short term, mortality was significantly reduced only in 'high risk' patients. Overall results with metoprolol have not demonstrated that early intervention treatment in all patients produces clinically important improvement in short term mortality. Thus, the use of metoprolol during the early stages of myocardial infarction is controversial, largely because of the requirement to treat all patients to save a small number at 'high risk'. This blanket coverage approach to treatment may be more justified during the post-infarction follow-up phase since it has been shown that metoprolol slightly, but significantly, reduces the mortality rate for periods of up to 3 years. Metoprolol is generally well tolerated and its beta 1-selectivity may facilitate its administration to certain patients (e.g. asthmatics and diabetics) in whom non-selective beta-blockers are contraindicated. Temporary fatigue, dizziness and headache are among the most frequently reported side effects. After a decade of use, metoprolol is well established as a first choice drug in mild to moderate hypertension and stable angina, and is beneficial in post-infarction patients. Further study is needed in less well established areas of treatment such as cardiac arrhythmias, idiopathic dilated cardiomyopathy and hypertensive cardiomegaly.
Metoprolol CR/XL in patients with heart failure: A pilot study examining the tolerability, safety, and effect on left ventricular ejection fraction. [2019]This study was designed to investigate the tolerability, safety, and effect on left ventricular function of a new long-acting preparation of metoprolol, metoprolol succinate (CR/XL).
Effect of controlled release/extended release metoprolol on carotid intima-media thickness in patients with hypercholesterolemia: a 3-year randomized study. [2019]Beta-adrenergic blockade has in several studies been shown to improve survival after myocardial infarction. In animal experiments beta-blockers have also shown an antiatherosclerotic effect. The aim of this study was to test the hypothesis that the beta-blocker metoprolol succinate controlled release/extended release (CR/XL), when given to patients with hypercholesterolemia on concomitant lipid-lowering therapy, provides an additional antiatherosclerotic effect to that provided by the statins, measured as carotid intima-media thickness (IMT).
[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]Metoprolol has not yet been systematically studied in terms of quality of life and incidence of adverse drug reactions (ADRs). Metoprolol is metabolized by polymorphic CYP2D6, therefore poor CYP2D6 metabolizers may be at higher risk of ADRs. Therefore, it is to be proven whether genotyping is useful to guide initial dose selection. In the ongoing UNAMET study, nonrandomized out-patients start treatment with metoprolol for various disorders. With the use of standard questionnaires, the patients are prospectively evaluated for common ADRs (headache, dizziness, tiredness, sleep disturbances, dyspnea, cold extremities, sexual dysfunction) and quality of life. The questionnaires are filled out before and until 6 weeks after initiating therapy; blood pressure and heart rate are also measured. The acquired data are then related to the patients' metoprolol dose and plasma concentrations, as well as to their metabolic ratio of metoprolol/alpha-OH-metoprolol and CYP2D6 genotype.
Actions of non-cardiodepressant beta-adrenergic blocking agents in hemorrhagic shock. [2014]Two new beta-adrenergic blocking agents, timolol and MK-761, were found to effectively antagonize the positive inotropic effects of isoproterenol on isolated cat papillary muscles without depressing contractile force. However, appropriate doses of these beta-adrenergic blockers (ie, 12.5--25 microgram/kg) did not significantly prolong survival in hemorrhagic shock in anesthetized cats. MK-761 prevented some of the plasma accumulations of myocardial depressant factor (MDF) during shock. Nevertheless both beta-blockers failed to prevent the accumulation of the lysosomal protease cathepsin D or peptide fragments (ie, amino-nitrogen groups) in the blood during shock. We conclude that neither agent is of significant benefit in severe hemorrhagic shock, and probably beta-adrenergic blockade is not a productive approach to pursue in the therapeutics of hemorrhagic shock.
Prevention of Syncope Trial (POST): a randomized, placebo-controlled study of metoprolol in the prevention of vasovagal syncope. [2022]Previous studies that assessed the effects of beta-blockers in preventing vasovagal syncope provided mixed results. Our goal was to determine whether treatment with metoprolol reduces the risk of syncope in patients with vasovagal syncope.