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
|Condition or disease||Intervention/treatment||Phase|
|Encephalopathy, Hypoxic-Ischemic||Drug: Clonidine (Duraclon®)||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||13 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
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.
- 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).
- 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
- Presence of Shivering After Clonidine [ Time Frame: 48hrs ]Babies were assessed after administration of clonidine for the presence or absence of shivering.
- 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
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
|United States, Maryland|
|Johns Hopkins Hospital|
|Baltimore, Maryland, United States, 21287|
|Principal Investigator:||Estelle B Gauda, MD||Johns Hopkins University|