Back to resultsEsmolol for the Treatment of Hypertension After Intracerebral Hemorrhage Study (ETHICHS) (ETHICHS)
Primary Purpose
Hemorrhagic Stroke
Status
Terminated
Phase
Phase 4
Locations
Brazil
Study Type
Interventional
Intervention
Brevibloc, 10 Mg/mL Intravenous Solution
Nitroprusside, Sodium
Sponsored by
About this trial
This is an interventional treatment trial for Hemorrhagic Stroke
Eligibility Criteria
Inclusion Criteria:
- Signature of the TCLE by participant or companion.
- 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.
- Intracerebral hemorrhage (volume < 30 cm3).
- No immediate surgical indication.
- Both sexes, aged above 18 years.
- Systolic blood pressure (> 150 mmHg and < 220 mmHg) measured on two occasions with a minimum difference of 2 minutes.
Exclusion Criteria:
- Cerebral hemorrhage secondary to structural lesions in the brain, vascular malformations, coagulopathies or traumatic brain injury, if known at the time of randomization.
- Participant in deep coma, defined by the Glasgow Coma Scale score of 3 to 5.
- Uncontrolled asthmatic or COPD participants, if known at the time of randomization.
- Participants with Grade IV Heart Failure, defined as heart rate < 50 beats per minute.
- Previous hemorrhagic stroke, if known at the time of randomization
- Participants with Cerebral Vascular Stroke.
- Participants who have presented previous ischemic cerebrovascular accident, if known at the time of randomization.
- Chronic diseases with life expectancy less than 3 months.
- Score ≥ 4 on the ICH score at the time of recruitment.
- In use of anticoagulants in the last 48 hours, if known at the time of randomization.
- Patients with contraindication to any of the study medications.
- Intubation Orotraqueal on arrival at the service.
- Pheochromocytoma, if known at the time of randomization.
- Patients with hyperthyroidism, if known at the time of randomization.
- Known pregnancy or breastfeeding . At the discretion of the investigator, an examination for confirmation may be requested.
Sites / Locations
- Hospital São Rafael
- Hospital Geral de Fortaleza
- Hospital Madre Teresa
- Hospital de Clínicas de Porto Alegre
- Hospital das Clínicas da Faculdade de Medicina de Botucatu
- Hospital das Clínicas de Riberião Preto
- Universidade Federal de São Paulo
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Brevibloc, 10 Mg/mL Intravenous Solution
Nitroprusside, Sodium
Arm Description
10 mL/h every 5 minutes until reaching the pressure target
0.5 mcg / kg / min every 3 minutes until reaching the pressure target
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
To compare the percentage of participants
To compare the percentage of participants with controlled systolic pressure (goal ≤ 140 mmHg)
Rankin Scale
To compare the ranks of the modified Rankin Scale (Applied by blind-investigator) between groups.
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.
MOCA scale
To compare the cognitive performance assessed between the groups.
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
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.
Adverse events related with investigational product
To compare the frequency and intensity of adverse events related to the use of research products between groups.
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.
Bradycardia
Compare the frequency and duration of major bradycardia (<50 beats per minute) between groups.
QT interval variability
Compare the QT interval variability measured by Holter during the infusion period of the investigational products between the groups
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.
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.
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
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.
Full Information
NCT ID
NCT03743103
First Posted
November 13, 2018
Last Updated
February 7, 2023
Sponsor
Cristália Produtos Químicos Farmacêuticos Ltda.
1. Study Identification
Unique Protocol Identification Number
NCT03743103
Brief Title
Esmolol for the Treatment of Hypertension After Intracerebral Hemorrhage Study (ETHICHS)
Acronym
ETHICHS
Official Title
A Randomized, Exploratory, Open-label, Phase IV, Blinded Endpoint, Multicenter and Prospective Study to Evaluate the Effect of the Addition of Esmolol on the Current Therapeutic Regimen Used for the Treatment of Hemorrhagic Stroke
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Terminated
Why Stopped
Low enrollement
Study Start Date
April 18, 2019 (Actual)
Primary Completion Date
October 31, 2021 (Actual)
Study Completion Date
October 31, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cristália Produtos Químicos Farmacêuticos Ltda.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemorrhagic Stroke
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Brevibloc, 10 Mg/mL Intravenous Solution
Arm Type
Experimental
Arm Description
10 mL/h every 5 minutes until reaching the pressure target
Arm Title
Nitroprusside, Sodium
Arm Type
Active Comparator
Arm Description
0.5 mcg / kg / min every 3 minutes until reaching the pressure target
Intervention Type
Drug
Intervention Name(s)
Brevibloc, 10 Mg/mL Intravenous Solution
Other Intervention Name(s)
Brevibloc
Intervention Description
10 mL/h every 5 minutes until reaching the pressure target
Intervention Type
Drug
Intervention Name(s)
Nitroprusside, Sodium
Other Intervention Name(s)
Nitroprus
Intervention Description
0.5 ug/kg/min every 3 minutes until reaching the pressure target
Primary Outcome Measure Information:
Title
To evaluate comparatively the drug test and the comparator drug
Description
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 Outcome Measure Information:
Title
To compare the percentage of participants
Description
To compare the percentage of participants with controlled systolic pressure (goal ≤ 140 mmHg)
Time Frame
in the first hour of treatment between the groups.
Title
Rankin Scale
Description
To compare the ranks of the modified Rankin Scale (Applied by blind-investigator) between groups.
Time Frame
in 90 ± 4 days
Title
NIH Stroke Scale (NIHSS) and Glasgow Coma Scale
Description
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
Title
MOCA scale
Description
To compare the cognitive performance assessed between the groups.
Time Frame
in 90 ± 4 days
Title
Hematoma volume expansion and perihematoma volume of cerebral edema
Description
To compare the percentages of between admission tomography and control tomography after the end of infusion of investigational products
Time Frame
24 ± 4 hours
Title
Severe hypotensive events with clinical consequences
Description
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
Title
Adverse events related with investigational product
Description
To compare the frequency and intensity of adverse events related to the use of research products between groups.
Time Frame
in 90 ± 4 days
Title
Severe cardiovascular events
Description
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
Title
Bradycardia
Description
Compare the frequency and duration of major bradycardia (<50 beats per minute) between groups.
Time Frame
in 90 ± 4 days
Title
QT interval variability
Description
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
Title
Frequency of changes in the ECO
Description
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
Title
Frequency of changes in the level of BNP
Description
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
Title
Frequency of changes in baseline cardiac troponin levels
Description
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
Title
Frequency of intra-cranial hypertension
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signature of the TCLE by participant or companion.
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.
Intracerebral hemorrhage (volume < 30 cm3).
No immediate surgical indication.
Both sexes, aged above 18 years.
Systolic blood pressure (> 150 mmHg and < 220 mmHg) measured on two occasions with a minimum difference of 2 minutes.
Exclusion Criteria:
Cerebral hemorrhage secondary to structural lesions in the brain, vascular malformations, coagulopathies or traumatic brain injury, if known at the time of randomization.
Participant in deep coma, defined by the Glasgow Coma Scale score of 3 to 5.
Uncontrolled asthmatic or COPD participants, if known at the time of randomization.
Participants with Grade IV Heart Failure, defined as heart rate < 50 beats per minute.
Previous hemorrhagic stroke, if known at the time of randomization
Participants with Cerebral Vascular Stroke.
Participants who have presented previous ischemic cerebrovascular accident, if known at the time of randomization.
Chronic diseases with life expectancy less than 3 months.
Score ≥ 4 on the ICH score at the time of recruitment.
In use of anticoagulants in the last 48 hours, if known at the time of randomization.
Patients with contraindication to any of the study medications.
Intubation Orotraqueal on arrival at the service.
Pheochromocytoma, if known at the time of randomization.
Patients with hyperthyroidism, if known at the time of randomization.
Known pregnancy or breastfeeding . At the discretion of the investigator, an examination for confirmation may be requested.
Facility Information:
Facility Name
Hospital São Rafael
City
Salvador
State/Province
Bahia
ZIP/Postal Code
04011-032
Country
Brazil
Facility Name
Hospital Geral de Fortaleza
City
Fortaleza
State/Province
Ceará
ZIP/Postal Code
60150-160
Country
Brazil
Facility Name
Hospital Madre Teresa
City
Belo Horizonte
State/Province
Minas Gerais
ZIP/Postal Code
30380-090
Country
Brazil
Facility Name
Hospital de Clínicas de Porto Alegre
City
Porto Alegre
State/Province
Rio Grande Do Sul
ZIP/Postal Code
90035-903
Country
Brazil
Facility Name
Hospital das Clínicas da Faculdade de Medicina de Botucatu
City
Botucatu
State/Province
São Paulo
ZIP/Postal Code
18607-741
Country
Brazil
Facility Name
Hospital das Clínicas de Riberião Preto
City
Ribeirão Preto
State/Province
São Paulo
ZIP/Postal Code
14015-130
Country
Brazil
Facility Name
Universidade Federal de São Paulo
City
São Paulo
ZIP/Postal Code
04022-002
Country
Brazil
12. IPD Sharing Statement
Learn more about this trial
Esmolol for the Treatment of Hypertension After Intracerebral Hemorrhage Study (ETHICHS)
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