Esmolol for the Treatment of Hypertension After Intracerebral Hemorrhage Study (ETHICHS)

Phase 4TerminatedNCT03743103

Cristália Produtos Químicos Farmacêuticos Ltda.20 enrolled

Overview

Because of its pharmacokinetic characteristics, such as short half-life and its safety profile, esmolol hydrochloride is a beta blocker suitable for venous use in the form of continuous infusion. Strategies that improve the blood pressure control of patients with hemorrhagic stroke during the first hours of hospitalization are determinant in controlling the hematoma expansion and determining factor in its prognosis. This study was designed with the objective of evaluating the beneficial effects of combining esmolol hydrochloride with sodium nitroprusside for the blood pressure control of participants with hemorrhagic stroke.

Participants with parenchymal intracranial hemorrhage (diagnosis confirmed by computed tomography or magnetic resonance imaging), and: * with systolic pressure \> 150 mmHg, * not contraindicated for treatment with beta-blockers, * who can start the drug treatment within 6 hours of the stroke, * having a target of ≤ 140 mmHg of systolic pressure within 1 hour after initiation of treatment.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hemorrhagic Stroke

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Signature of the TCLE by participant or companion. 2. Spontaneous intracerebral hemorrhage confirmed by computed tomography or magnetic resonance imaging and fit to be included in the study and initiate therapy with study medications within 6 hours after the event. 3. Intracerebral hemorrhage (volume \< 30 cm3). 4. No immediate surgical indication. 5. Both sexes, aged above 18 years. 6. Systolic blood pressure (\> 150 mmHg and \< 220 mmHg) measured on two occasions with a minimum difference of 2 minutes. Exclusion Criteria: 1. Cerebral hemorrhage secondary to structural lesions in the brain, vascular malformations, coagulopathies or traumatic brain injury, if known at the time of randomization. 2. Participant in deep coma, defined by the Glasgow Coma Scale score of 3 to 5. 3. Uncontrolled asthmatic or COPD participants, if known at the time of randomization. 4. Participants with Grade IV Heart Failure, defined as heart rate \< 50 beats per minute. 5. Previous hemorrhagic stroke, if known at the time of randomization 6. Participants with Cerebral Vascular Stroke. 7. Participants who have presented previous ischemic cerebrovascular accident, if known at the time of randomization. 8. Chronic diseases with life expectancy less than 3 months. 9. Score ≥ 4 on the ICH score at the time of recruitment. 10. In use of anticoagulants in the last 48 hours, if known at the time of randomization. 11. Patients with contraindication to any of the study medications. 12. Intubation Orotraqueal on arrival at the service. 13. Pheochromocytoma, if known at the time of randomization. 14. Patients with hyperthyroidism, if known at the time of randomization. 15. Known pregnancy or breastfeeding . At the discretion of the investigator, an examination for confirmation may be requested.

Locations (7)

Hospital Geral de Fortaleza

Fortaleza, Ceará, Brazil

Hospital São Rafael

Salvador, Estado de Bahia, Brazil

Hospital Madre Teresa

Belo Horizonte, Minas Gerais, Brazil

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Hospital das Clínicas da Faculdade de Medicina de Botucatu

Botucatu, São Paulo, Brazil

Hospital das Clínicas de Riberião Preto

Ribeirão Preto, São Paulo, Brazil

Universidade Federal de São Paulo

São Paulo, Brazil

Outcomes

Primary Outcomes

To evaluate comparatively the drug test and the comparator drug

Variation of systolic and diastolic pressure during the time of use of the investigational products measured by ABPM (outpatient blood pressure monitoring).

Time frame: 7 days

Secondary Outcomes

To compare the percentage of participants

To compare the percentage of participants with controlled systolic pressure (goal ≤ 140 mmHg)

Time frame: in the first hour of treatment between the groups.

Rankin Scale

To compare the ranks of the modified Rankin Scale (Applied by blind-investigator) between groups.

Time frame: in 90 ± 4 days

NIH Stroke Scale (NIHSS) and Glasgow Coma Scale

Compare the variation in scores on the NIH Stroke Scale (NIHSS) and Glasgow Coma Scale (whichever comes first) between groups.

Time frame: from admission to discharge or 7th day

MOCA scale

To compare the cognitive performance assessed between the groups.

Time frame: in 90 ± 4 days

Hematoma volume expansion and perihematoma volume of cerebral edema

To compare the percentages of between admission tomography and control tomography after the end of infusion of investigational products

Time frame: 24 ± 4 hours

Severe hypotensive events with clinical consequences

To compare the frequency of severe hypotensive events with clinical consequencesrequiring corrective therapy with vasopressors during the use of investigational products between groups.

Time frame: in 90 ± 4 days

Adverse events related with investigational product

To compare the frequency and intensity of adverse events related to the use of research products between groups.

Time frame: in 90 ± 4 days

Severe cardiovascular events

Compare the frequency of severe cardiovascular events (acute myocardial infarction, cardiac arrest, arrhythmias, or the development of severe congestive heart failure) or major neurological complications (eg need for neurosurgery, intraventricular bypass placement, cerebral infarction, convulsive seizures, intoxication, neurological toxicity) within the first 90 days of follow-up between groups.

Time frame: in 90 ± 4 days

Bradycardia

Compare the frequency and duration of major bradycardia (\<50 beats per minute) between groups.

Time frame: in 90 ± 4 days

QT interval variability

Compare the QT interval variability measured by Holter during the infusion period of the investigational products between the groups

Time frame: during the infusion period

Frequency of changes in the ECO

Compare the frequency of changes in the Echocardiogram (Differences observed between the examination performed in the first 72 ± 4 hours and the return after 90 ± 3 days) between the groups.

Time frame: in the first 72 ± 4 hours and the return after 90 ± 3 days

Frequency of changes in the level of BNP

To compare the frequency of changes in the level of B-type natriuretic peptide (BNP) measured at baseline times, 24 ± 4 and 72 ± 4 hours between groups.

Time frame: at baseline times, 24 ± 4 and 72 ± 4 hours

Frequency of changes in baseline cardiac troponin levels

To compare the frequency of changes in baseline cardiac troponin levels, 24 ± 4 and 72 ± 4 hours

Time frame: 24 ± 4 and 72 ± 4 hours

Frequency of intra-cranial hypertension

To compare the frequency of intra-cranial hypertension diagnosed by measuring the diameter of the optic nerve sheath by transorbital ultrasound daily for 7 days or high, whichever occurs first between the groups.

Time frame: 7 days