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Trial record 6 of 326 for:    clonidine

Safety of Clonidine in Infants With Hypoxic Ischemic Encephalopathy During Therapeutic Hypothermia (HIE)

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ClinicalTrials.gov Identifier: NCT01862250
Recruitment Status : Completed
First Posted : May 24, 2013
Results First Posted : January 5, 2018
Last Update Posted : January 5, 2018
Sponsor:
Collaborator:
University of Maryland, College Park
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:
This research is being done to find out the safety of the investigational study drug, Clonidine Hydrochloride ( CLON). , in infants who are undergoing whole body cooling for the treatment of hypoxic ischemic encephalopathy (HIE). The only known and effective treatment for HIE is therapeutic hypothermia or whole body cooling for72 hours. During the cooling process, babies get agitated, shiver and are uncomfortable. To treat these side effects morphine is frequently used. CLON is very effective in decreasing shivering in adults and children. Furthermore, in some preclinical studies, clonidine has been shown to be neuroprotective (safe for the brain in models of brain injury)..This is a Phase I-II to determine if low dose CLON will reduce the incidence of shivering and whether it has short term cardiovascular safety. In this Phase I-II study, the investigators will determine the (i) the maximum tolerated dose of CLON during cooling for HIE, (ii) the effects of CLON on heart rate, blood pressure, core body temperature and cerebral autoregulation (ability to maintain constant blood flow to the brain) and (iii) association between blood levels and changes in the above parameters. In this study the investigators hope to find ways to improve sedation, shivering and agitation in newborn infants with HIE on the cooling protocol. Our ultimate goal is determine the potential neuro-protective properties of clonidine in newborn babies with HIE.

Condition or disease Intervention/treatment Phase
Encephalopathy, Hypoxic-Ischemic Drug: Clonidine (Duraclon®) Phase 1 Phase 2

Detailed Description:

The most desirable sedative-analgesic agent used in infants with HIE would 1) have an excellent safety profile, 2) provide adequate analgesia and sedation, 3) reduce shivering, 4) cause minimal respiratory depression, 5) preserve cerebrovascular autoregulation, and 6) confer neuroprotection. Several lines of evidence suggest alpha 2 adrenergic receptor agonist class of sedatives-analgesics may have all these properties. The investigators have recently developed a sensitive assay to measure clonidine levels which will allow us to perform population Pharmacokinetic (PK)/Pharmacodynamic (PD) analyses of clonidine in sick newborns. Thus, this phase I/II trial is designed to test the hypothesis clonidine , an alpha- 2 adrenergic receptor agonist, will reduce the incidence of shivering without adversely affecting heart rate (HR), blood pressure (BP), temperature regulation or cerebrovascular autoregulation.

Essentially all classes of sedative-analgesic agents affect mean arterial blood pressure (MAP) which can alter cerebral perfusion and affect cerebrovascular autoregulation. Cerebrovascular autoregulation is when blood flow to the brain is held relatively constant over a wide range of MAPs; it ensures a steady supply of oxygenated blood to the brain, and is only functional within a specific range of MAP's. When MAP deviates from this range and drops below the lower limit of autoregulation, blood flow becomes passive to MAP and the brain is placed at risk for ischemic injury. Brain injury alters cerebrovascular autoregulation in the region of injury, and together with sub-optimal MAP after hypoxic brain injury could cause more brain ischemia leading to poor outcomes, seizures, and permanent neurologic injuries. Little information is available on the effect of HIE alone or in combination with hypothermia on cerebrovascular autoregulation, and no information is published on the direct effect of sedative-analgesics on alterations in hemodynamic parameters and subsequent indirect or direct effects on cerebrovascular autoregulation in newborns with HIE. Thus, this study will establish the safety of clonidine, a commonly used sedative-analgesic in infants and children, in a population of infants with HIE undergoing therapeutic hypothermia. A secondary exploratory outcome is to determine the efficacy of clonidine in reducing shivering during the cooling phase of the therapeutic hypothermia protocol.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I-II Clinical Trial to Determine the Safety of Clonidine in Infants With Hypoxic Ischemic Encephalopathy During Therapeutic Hypothermia
Actual Study Start Date : October 3, 2013
Actual Primary Completion Date : April 14, 2015
Actual Study Completion Date : April 14, 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hypothermia

Arm Intervention/treatment
Experimental: Clonidine infants with HIE
Infants in this group will receive Intravenous clonidine at 1µg/kg/dose either every 6 or 8 hrs from the start of cooling to the end of re-warming
Drug: Clonidine (Duraclon®)

Clonidine at dosing intervals of 6, 8, 12, 18 or 24 hours. If the following is observed the event will be recorded, and no additional clonidine will be given and blood will be drawn to measure plasma level of clondine.

  • 10 mm Hg reduction in MAP or MAP ≤ 40 mm Hg sustained for ≥30 min after administration
  • 20% drop in HR from the infant's baseline, sustained for ≥30 min after administration
  • HR ≤70/min, sustained for ≥30 min after administration




Primary Outcome Measures :
  1. Steady State Clonidine Blood Levels During Hypothermia [ Time Frame: 3 days ]

    Trough clonidine blood levels were measured after 4-7 doses of clonidine were given intravenously with a dosing interval of every 8 hrs. Mean and standard deviation (SD) of the number of doses given prior to levels being drawn was 5.3 (mean) and 0.37 (SD).

    Time after last dose before measurement was 9hrs (mean) and 2.7hrs (SD).


  2. Amount of Morphine Given [ Time Frame: Up to 2 days ]
    Intravenous morphine (mg/kg) was given. The standard dose is 0.05 mg/kg per dose


Secondary Outcome Measures :
  1. Presence of Shivering After Clonidine [ Time Frame: 48hrs ]
    Babies were assessed after administration of clonidine for the presence or absence of shivering.

  2. Time to Passive Rewarming [ Time Frame: Beginning at 72 hours up to 12 hours ]
    Following 2 hours of therapeutic hypothermia, the temperature of the thermo-blanket is adjusted up half degree per hour allowing passive rewarming until 36.5 degrees is reached



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Ages Eligible for Study:   35 Weeks to 42 Weeks   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Infants ≥35 0/7 weeks gestation with the diagnosis of HIE who are being treated with therapeutic hypothermia, who have indwelling arterial lines
  • Informed parental consent

Exclusion Criteria:

  • Infants who are considered moribund and the clinical team is considering withdrawal of support
  • Infants who need > 20 µg/kg/min of dopamine or the addition of epinephrine or dobutamine to maintain a mean arterial pressure (MAP) ≥ 45 mmHg, or milrinone for cardiovascular support
  • Baseline heart rate (HR) <80 bpm during hypothermia
  • Infants suspected of major chromosomal anomalies, except trisomy 21
  • Infants with major cardiovascular anomalies
  • Infants with severe persistent pulmonary hypertension of the newborn who are enrolled and who then need Extracorporal Membrane Oxygenation (ECMO) will be withdrawn from the study

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): NCT01862250


Locations
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United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Johns Hopkins University
University of Maryland, College Park
Investigators
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Principal Investigator: Estelle B Gauda, MD Johns Hopkins University

Publications:
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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01862250     History of Changes
Obsolete Identifiers: NCT02252848
Other Study ID Numbers: ID: NA_00072308
First Posted: May 24, 2013    Key Record Dates
Results First Posted: January 5, 2018
Last Update Posted: January 5, 2018
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Clonidine
Brain Diseases
Brain Ischemia
Hypoxia-Ischemia, Brain
Hypoxia, Brain
Ischemia
Hypothermia
Hypoxia
Pathologic Processes
Central Nervous System Diseases
Nervous System Diseases
Body Temperature Changes
Signs and Symptoms
Signs and Symptoms, Respiratory
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action