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

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ClinicalTrials.gov Identifier: NCT03743103
Recruitment Status : Not yet recruiting
First Posted : November 15, 2018
Last Update Posted : November 15, 2018
Sponsor:
Information provided by (Responsible Party):
Cristália Produtos Químicos Farmacêuticos Ltda.

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.

Condition or disease Intervention/treatment Phase
Hemorrhagic Stroke Drug: Brevibloc, 10 Mg/mL Intravenous Solution Drug: Nitroprusside, Sodium Phase 4

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : December 10, 2018
Estimated Primary Completion Date : February 28, 2020
Estimated Study Completion Date : May 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Brevibloc, 10 Mg/mL Intravenous Solution
10 mL/h every 5 minutes until reaching the pressure target
Drug: Brevibloc, 10 Mg/mL Intravenous Solution
10 mL/h every 5 minutes until reaching the pressure target
Other Name: Brevibloc

Drug: Nitroprusside, Sodium
0.5 ug/kg/min every 3 minutes until reaching the pressure target
Other Name: Nitroprus

Active Comparator: Nitroprusside, Sodium
0.5 mcg / kg / min every 3 minutes until reaching the pressure target
Drug: Nitroprusside, Sodium
0.5 ug/kg/min every 3 minutes until reaching the pressure target
Other Name: Nitroprus




Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. To compare the percentage of participants [ Time Frame: in the first hour of treatment between the groups. ]
    To compare the percentage of participants with controlled systolic pressure (goal ≤ 140 mmHg)

  2. Rankin Scale [ Time Frame: in 90 ± 4 days ]
    To compare the ranks of the modified Rankin Scale (Applied by blind-investigator) between groups.

  3. NIH Stroke Scale (NIHSS) and Glasgow Coma Scale [ Time Frame: from admission to discharge or 7th day ]
    Compare the variation in scores on the NIH Stroke Scale (NIHSS) and Glasgow Coma Scale (whichever comes first) between groups.

  4. MOCA scale [ Time Frame: in 90 ± 4 days ]
    To compare the cognitive performance assessed between the groups.

  5. Hematoma volume expansion and perihematoma volume of cerebral edema [ Time Frame: 24 ± 4 hours ]
    To compare the percentages of between admission tomography and control tomography after the end of infusion of investigational products

  6. Severe hypotensive events with clinical consequences [ Time Frame: in 90 ± 4 days ]
    To compare the frequency of severe hypotensive events with clinical consequencesrequiring corrective therapy with vasopressors during the use of investigational products between groups.

  7. Adverse events related with investigational product [ Time Frame: in 90 ± 4 days ]
    To compare the frequency and intensity of adverse events related to the use of research products between groups.

  8. Severe cardiovascular events [ Time Frame: in 90 ± 4 days ]
    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.

  9. Bradycardia [ Time Frame: in 90 ± 4 days ]
    Compare the frequency and duration of major bradycardia (<50 beats per minute) between groups.

  10. QT interval variability [ Time Frame: during the infusion period ]
    Compare the QT interval variability measured by Holter during the infusion period of the investigational products between the groups

  11. Frequency of changes in the ECO [ Time Frame: in the first 72 ± 4 hours and the return after 90 ± 3 days ]
    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.

  12. Frequency of changes in the level of BNP [ Time Frame: at baseline times, 24 ± 4 and 72 ± 4 hours ]
    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.

  13. Frequency of changes in baseline cardiac troponin levels [ Time Frame: 24 ± 4 and 72 ± 4 hours ]
    To compare the frequency of changes in baseline cardiac troponin levels, 24 ± 4 and 72 ± 4 hours

  14. Frequency of intra-cranial hypertension [ Time Frame: 7 days ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03743103


Contacts
Contact: Octavio M Pontes Neto, MD, PhD +5516981013465 opontesneto@fmrp.usp.br
Contact: Ricardo Baradelli +551137236571 ricardo.baradelli@cristalia.com.br

Locations
Brazil
Hospital São Rafael Not yet recruiting
Salvador, Bahia, Brazil, 04011-032
Contact: Rogério H Passos, MD         
Principal Investigator: Rogério H Passos, MD         
Hospital Geral de Fortaleza Not yet recruiting
Fortaleza, Ceará, Brazil, 60150-160
Contact: Fabrício O Lima, MD         
Principal Investigator: Fabrício O Lima, MD         
Hospital Madre Teresa Not yet recruiting
Belo Horizonte, Minas Gerais, Brazil, 30380-090
Contact: Fidel CA Meira, MD         
Principal Investigator: Fidel CA Meira, MD         
Hospital de Clínicas de Porto Alegre Not yet recruiting
Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
Contact: Sheila CO Martins, MD, PhD         
Principal Investigator: Sheila CO Martins, MD, PhD         
Hospital das Clínicas da Faculdade de Medicina de Botucatu Not yet recruiting
Botucatu, São Paulo, Brazil, 18607-741
Contact: Rodrigo Bazan, MD         
Principal Investigator: Rodrigo Bazan, MD         
Hospital das Clínicas de Riberião Preto Not yet recruiting
Ribeirão Preto, São Paulo, Brazil, 14015-130
Contact: Octávio M Pontes Neto, MD, PhD         
Principal Investigator: Octávio M Pontes Neto, MD, PhD         
Universidade Federal de São Paulo Not yet recruiting
São Paulo, Brazil, 04022-002
Contact: Gisele S Silva, MD         
Principal Investigator: Gisele S Silva, MD         
Sponsors and Collaborators
Cristália Produtos Químicos Farmacêuticos Ltda.

Responsible Party: Cristália Produtos Químicos Farmacêuticos Ltda.
ClinicalTrials.gov Identifier: NCT03743103     History of Changes
Other Study ID Numbers: CRT088
First Posted: November 15, 2018    Key Record Dates
Last Update Posted: November 15, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Cardiovascular Diseases
Stroke
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Hemorrhage
Pathologic Processes
Esmolol
Nitroprusside
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antihypertensive Agents
Vasodilator Agents
Nitric Oxide Donors