Hemorrhagic StrokePhase 4ETHICHSNCT03743103
Esmolol for the Treatment of Hypertension After Intracerebral Hemorrhage Study (ETHICHS)
A Phase 4 study testing Brevibloc, 10 Mg/mL Intravenous Solution and Nitroprusside, Sodium in people with Hemorrhagic Stroke, run by Cristália Produtos Químicos Farmacêuticos Ltda. at 7 sites in Brazil.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hemorrhagic Stroke
- What is being tested?
- Brevibloc, 10 Mg/mL Intravenous Solution and Nitroprusside, Sodium
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 7 sitesBrazil
- Study dates
- 18 Apr 2019to 31 Oct 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Brazil7 sites
Hospital Madre Teresa
Belo Horizonte, Minas Gerais, 30380-090
Hospital das Clínicas da Faculdade de Medicina de Botucatu
Botucatu, São Paulo, 18607-741
Hospital Geral de Fortaleza
Fortaleza, Ceará, 60150-160
Hospital de Clínicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035-903
Hospital das Clínicas de Riberião Preto
Ribeirão Preto, São Paulo, 14015-130
Hospital São Rafael
Salvador, Estado de Bahia, 04011-032
Universidade Federal de São Paulo
São Paulo, 04022-002
About this study
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
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.
Read the 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.
- Conditions
- Hemorrhagic Stroke
- Being tested
- Brevibloc, 10 Mg/mL Intravenous Solution, Nitroprusside, Sodium
- Medical subject headings
- Hemorrhagic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Brevibloc, 10 Mg/mL Intravenous SolutionDrug
Also called Brevibloc
10 mL/h every 5 minutes until reaching the pressure target
Nitroprusside, SodiumDrug
Also called Nitroprus
0.5 ug/kg/min every 3 minutes until reaching the pressure target
| Study group | Role | What they receive |
|---|---|---|
| Brevibloc, 10 Mg/mL Intravenous Solution | Experimental | 10 mL/h every 5 minutes until reaching the pressure target Receives: Drug: Brevibloc, 10 Mg/mL Intravenous Solution; Drug: Nitroprusside, Sodium |
| Nitroprusside, Sodium | Active comparator | 0.5 mcg / kg / min every 3 minutes until reaching the pressure target Receives: Drug: Nitroprusside, Sodium |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 7 days
Secondary outcomes (14)
To compare the percentage of participants
To compare the percentage of participants with controlled systolic pressure (goal ≤ 140 mmHg)
Measured: 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.
Measured: 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.
Measured: from admission to discharge or 7th day
MOCA scale
To compare the cognitive performance assessed between the groups.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: in 90 ± 4 days
Bradycardia
Compare the frequency and duration of major bradycardia (<50 beats per minute) between groups.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2018
- Study start18 Apr 2019
- Primary completion31 Oct 2021
- Study completion31 Oct 2021
Why it stopped: Low enrollement
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hemorrhagic StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cristália Produtos Químicos Farmacêuticos Ltda.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03743103
- Sponsor's protocol ID
- CRT088
- Acronym
- ETHICHS
- Status last verified
- Jan 2023
- First submitted
- 13 Nov 2018
- Last updated
- 9 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03743103
- Acronym / sponsor ID
- ETHICHS / CRT088
- Conditions
- Hemorrhagic Stroke
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low enrollement
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Cristália Produtos Químicos Farmacêuticos Ltda.Industry (pharma, biotech, devices)
- Study start
- 18 Apr 2019 (actual)
- Primary completion
- 31 Oct 2021 (actual)
- Study completion
- 31 Oct 2021 (actual)
- First posted
- 15 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Brevibloc, 10 Mg/mL Intravenous Solution | Experimental | Drug: Brevibloc, 10 Mg/mL Intravenous Solution, Drug: Nitroprusside, Sodium10 mL/h every 5 minutes until reaching the pressure target |
| Nitroprusside, Sodium | Active comparator | Drug: Nitroprusside, Sodium0.5 mcg / kg / min every 3 minutes until reaching the pressure target |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Brevibloc, 10 Mg/mL Intravenous SolutionAlso: Brevibloc10 mL/h every 5 minutes until reaching the pressure target | Drug | Brevibloc, 10 Mg/mL Intravenous Solution |
| Nitroprusside, SodiumAlso: Nitroprus0.5 ug/kg/min every 3 minutes until reaching the pressure target | Drug | Brevibloc, 10 Mg/mL Intravenous Solution, Nitroprusside, Sodium |
Primary outcome
To evaluate comparatively the drug test and the comparator drug
Time frame: 7 days
Variation of systolic and diastolic pressure during the time of use of the investigational products measured by ABPM (outpatient blood pressure monitoring).
14 secondary outcomes
To compare the percentage of participants
Time frame: in the first hour of treatment between the groups.
Rankin Scale
Time frame: in 90 ± 4 days
NIH Stroke Scale (NIHSS) and Glasgow Coma Scale
Time frame: from admission to discharge or 7th day
MOCA scale
Time frame: in 90 ± 4 days
Hematoma volume expansion and perihematoma volume of cerebral edema
Time frame: 24 ± 4 hours
Severe hypotensive events with clinical consequences
Time frame: in 90 ± 4 days
Adverse events related with investigational product
Time frame: in 90 ± 4 days
Severe cardiovascular events
Time frame: in 90 ± 4 days
Bradycardia
Time frame: in 90 ± 4 days
QT interval variability
Time frame: during the infusion period
Frequency of changes in the ECO
Time frame: in the first 72 ± 4 hours and the return after 90 ± 3 days
Frequency of changes in the level of BNP
Time frame: at baseline times, 24 ± 4 and 72 ± 4 hours
Frequency of changes in baseline cardiac troponin levels
Time frame: 24 ± 4 and 72 ± 4 hours
Frequency of intra-cranial hypertension
Time frame: 7 days
Results and safety
The study was stopped early (reason given: Low enrollement). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Brevibloc, 10 Mg/mL Intravenous Solution and Nitroprusside, Sodium in people with Hemorrhagic Stroke, run by Cristália Produtos Químicos Farmacêuticos Ltda. at 7 sites in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Low enrollement). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate comparatively the drug test and the comparator drug (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2023.