Ignite Creation Date:
2024-10-26 @ 3:42 PM
Last Modification Date:
2024-10-26 @ 3:42 PM
Study NCT ID:
NCT06635707
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-09-14
Brief Title:
Efficacy and Safety Study of Urapidil Alone or With Esmolol in Treating Acute Hypertensive Intracerebral Hemorrhage
Sponsor:
None
Organization:
None
Study Overview
Official Title:
The Study on the Efficacy and Safety of Using Urapidil Alone or in Combination With Esmolol for the Treatment of Acute Hypertensive Intracerebral Hemorrhage A Prospective Open-label Observational Multicenter Research
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The objective of this study is to investigate the efficacy and safety of urapidil monotherapy versus the combination of esmolol in treating participants with acute hypertensive intracerebral hemorrhage through a prospective open-label observational multicenter clinical trial aiming to provide guidance for clinicians in formulating rational treatment plans
Detailed Description:
Hypertensive intracerebral hemorrhage HICH is a prevalent and severe condition that poses significant challenges to the medical community due to its harmful nature and complexity Over the past few decades there has been considerable controversy surrounding blood pressure management strategies for patients with acute HICH Both hypertension and hypotension following cerebral hemorrhage are associated with adverse outcomes Multiple trials aimed at reducing blood pressure in patients with acute cerebral hemorrhage have been conducted and among patients recruited within six hours of symptom onset blood pressure reduction has been linked to decreased hematoma expansion Current international guidelines from the European Stroke Organization the American Heart Association AHAAmerican Stroke Association and the Canadian Stroke Best Practice Recommendations support the prompt reduction of systolic blood pressure to 140 mmHg after symptom onset aiming to maintain systolic blood pressure between 130 and 150 mmHg However for certain patients such as those with extremely high blood pressure after ICH systolic blood pressure 220 mmHg a more individualized approach is necessary Notably patients with very high blood pressure systolic blood pressure 220 mmHg were not included in these trials and reducing systolic blood pressure to 140 mmHg in this population may be harmful associated with higher rates of neurological deterioration and adverse renal events
Elevated blood pressure BP is common in patients with acute spontaneous intracerebral hemorrhage ICH and is closely related to hematoma growth which is a crucial independent predictor of clinical deterioration and outcomes in ICH patients Previous studies have shown that hematoma growth primarily occurs within the first six hours after spontaneous cerebral hemorrhage Consequently early blood pressure reduction may be beneficial in preventing hematoma growth Research indicates that ICH patients who achieve target blood pressure more quickly are less likely to experience hematoma growth Specifically patients who reach a target systolic blood pressure SBP of 140 mmHg within the first hour after randomization exhibit a lower absolute hematoma growth rate Studies have supported the benefit of shortening the time to achieve target blood pressure in ICH patients corroborating these findings Hematoma growth is primarily attributed to ongoing bleeding and secondary vascular rupture occurring predominantly within the first six hours after ICH onset particularly during the initial 2-3 hours with a gradual decline in frequency over time
Changes in the autonomic nervous system ANS have been previously observed in acute stroke patients characterized by impaired cardiovascular regulation and altered balance between sympathetic and parasympathetic nerves Clinically significantly autonomic dysfunction is associated with poor prognosis increased mortality or sudden death after stroke Variations in heart rate variability HRV and baroreceptor sensitivity BRS have traditionally been considered surrogate markers of cardiovascular ANS modulation Previous studies on HRV in acute brain injury have primarily focused on ischemic cerebral infarction or traumatic brain injury TBI In both TBI and ischemic cerebral infarction HRV parameters have shown independent associations with outcomes
Urapidil URA is a selective α1-adrenoceptor antagonist that also acts as a central 5-HT1A receptor agonist exerting both peripheral and central hypotensive effects The hypotensive effect of URA is dose-dependent and may vary among individuals URA demonstrates a self-limiting hypotensive effect even at high doses without causing severe hypotension It reduces cardiac preload and afterload decreases myocardial oxygen consumption and increases cardiac output without causing reflex tachycardia or affecting heart rate Additionally URA does not increase intracranial pressure does not impair hemodynamics in the middle cerebral artery and is conducive to maintaining cerebral perfusion pressure Furthermore URA enhances renal blood flow reduces renal vascular resistance does not increase shunt fraction and does not decrease arterial oxygen partial pressure
Esmolol is an ultra-short-acting highly selective β1-blocker that competitively antagonizes β1 receptors in myocardial cells It exerts its pharmacological effects by blocking the activity of adrenaline and noradrenaline At high doses it may also block β2 receptors in airway and vascular smooth muscle At therapeutic doses esmolol has no intrinsic sympathomimetic activity or membrane-stabilizing effects When administered intravenously it takes effect within 60 seconds and its pharmacological effects disappear within 10 to 30 minutes after infusion cessation Electrophysiological studies suggest that esmolol exhibits typical β1-blocker effects including reduced heart rate prolonged sinus cycle length prolonged sinus node recovery time prolonged AH interval and antegrade Wenckebach period slowed conduction in atrial and ventricular myocardium and cardiac conduction system and prolonged refractoriness By blocking sympathetic excitation esmolol lowers the threshold for ventricular fibrillation VF
Patients with acute HICH often experience increased heart rate and uncontrolled blood pressure Previous studies have shown that the time taken to normalize blood pressure and heart rate variability are correlated with adverse outcomes in patients The present study aims to evaluate the effectiveness of urapidil alone and in combination with esmolol in reducing blood pressure and controlling heart rate in patients with acute
Elevated blood pressure BP is common in patients with acute spontaneous intracerebral hemorrhage ICH and is closely related to hematoma growth which is a crucial independent predictor of clinical deterioration and outcomes in ICH patients Previous studies have shown that hematoma growth primarily occurs within the first six hours after spontaneous cerebral hemorrhage Consequently early blood pressure reduction may be beneficial in preventing hematoma growth Research indicates that ICH patients who achieve target blood pressure more quickly are less likely to experience hematoma growth Specifically patients who reach a target systolic blood pressure SBP of 140 mmHg within the first hour after randomization exhibit a lower absolute hematoma growth rate Studies have supported the benefit of shortening the time to achieve target blood pressure in ICH patients corroborating these findings Hematoma growth is primarily attributed to ongoing bleeding and secondary vascular rupture occurring predominantly within the first six hours after ICH onset particularly during the initial 2-3 hours with a gradual decline in frequency over time
Changes in the autonomic nervous system ANS have been previously observed in acute stroke patients characterized by impaired cardiovascular regulation and altered balance between sympathetic and parasympathetic nerves Clinically significantly autonomic dysfunction is associated with poor prognosis increased mortality or sudden death after stroke Variations in heart rate variability HRV and baroreceptor sensitivity BRS have traditionally been considered surrogate markers of cardiovascular ANS modulation Previous studies on HRV in acute brain injury have primarily focused on ischemic cerebral infarction or traumatic brain injury TBI In both TBI and ischemic cerebral infarction HRV parameters have shown independent associations with outcomes
Urapidil URA is a selective α1-adrenoceptor antagonist that also acts as a central 5-HT1A receptor agonist exerting both peripheral and central hypotensive effects The hypotensive effect of URA is dose-dependent and may vary among individuals URA demonstrates a self-limiting hypotensive effect even at high doses without causing severe hypotension It reduces cardiac preload and afterload decreases myocardial oxygen consumption and increases cardiac output without causing reflex tachycardia or affecting heart rate Additionally URA does not increase intracranial pressure does not impair hemodynamics in the middle cerebral artery and is conducive to maintaining cerebral perfusion pressure Furthermore URA enhances renal blood flow reduces renal vascular resistance does not increase shunt fraction and does not decrease arterial oxygen partial pressure
Esmolol is an ultra-short-acting highly selective β1-blocker that competitively antagonizes β1 receptors in myocardial cells It exerts its pharmacological effects by blocking the activity of adrenaline and noradrenaline At high doses it may also block β2 receptors in airway and vascular smooth muscle At therapeutic doses esmolol has no intrinsic sympathomimetic activity or membrane-stabilizing effects When administered intravenously it takes effect within 60 seconds and its pharmacological effects disappear within 10 to 30 minutes after infusion cessation Electrophysiological studies suggest that esmolol exhibits typical β1-blocker effects including reduced heart rate prolonged sinus cycle length prolonged sinus node recovery time prolonged AH interval and antegrade Wenckebach period slowed conduction in atrial and ventricular myocardium and cardiac conduction system and prolonged refractoriness By blocking sympathetic excitation esmolol lowers the threshold for ventricular fibrillation VF
Patients with acute HICH often experience increased heart rate and uncontrolled blood pressure Previous studies have shown that the time taken to normalize blood pressure and heart rate variability are correlated with adverse outcomes in patients The present study aims to evaluate the effectiveness of urapidil alone and in combination with esmolol in reducing blood pressure and controlling heart rate in patients with acute
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None