Clinical trial NCT03743103: Esmolol for the Treatment of Hypertension After Intracerebral Hemorrhage Study (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
Overall status: TERMINATED
Phase: PHASE4
Conditions: Hemorrhagic Stroke
Lead sponsor: Cristália Produtos Químicos Farmacêuticos Ltda.
Sponsor class: INDUSTRY
First posted: 2018-11-15
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: To evaluate comparatively the drug test and the comparator drug
timeFrame: 7 days
Secondary outcomes:
measure: To compare the percentage of participants
timeFrame: in the first hour of treatment between the groups.
measure: Rankin Scale
timeFrame: in 90 ± 4 days
measure: NIH Stroke Scale (NIHSS) and Glasgow Coma Scale
timeFrame: from admission to discharge or 7th day
measure: MOCA scale
timeFrame: in 90 ± 4 days
measure: Hematoma volume expansion and perihematoma volume of cerebral edema
timeFrame: 24 ± 4 hours
measure: Severe hypotensive events with clinical consequences
timeFrame: in 90 ± 4 days
measure: Adverse events related with investigational product
timeFrame: in 90 ± 4 days
measure: Severe cardiovascular events
timeFrame: in 90 ± 4 days
measure: Bradycardia
timeFrame: in 90 ± 4 days
measure: QT interval variability
timeFrame: during the infusion period
measure: Frequency of changes in the ECO
timeFrame: in the first 72 ± 4 hours and the return after 90 ± 3 days
measure: Frequency of changes in the level of BNP
timeFrame: at baseline times, 24 ± 4 and 72 ± 4 hours
measure: Frequency of changes in baseline cardiac troponin levels
timeFrame: 24 ± 4 and 72 ± 4 hours
measure: Frequency of intra-cranial hypertension
timeFrame: 7 days
Other outcomes:
Locations:
city: Salvador
country: Brazil
facility: Hospital São Rafael
state: Bahia
city: Fortaleza
country: Brazil
facility: Hospital Geral de Fortaleza
state: Ceará
city: Belo Horizonte
country: Brazil
facility: Hospital Madre Teresa
state: Minas Gerais
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
state: Rio Grande Do Sul
city: Botucatu
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina de Botucatu
state: São Paulo
city: Ribeirão Preto
country: Brazil
facility: Hospital das Clínicas de Riberião Preto
state: São Paulo
city: São Paulo
country: Brazil
facility: Universidade Federal de São Paulo
Study officials:
References: