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Hypoxic-Ischemic Encephalopathy Therapy Optimization in Neonates for Better Neuroprotection With Inhalative CO2 (HENRIC)

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ClinicalTrials.gov Identifier: NCT02700854
Recruitment Status : Recruiting
First Posted : March 7, 2016
Last Update Posted : March 17, 2017
Sponsor:
Information provided by (Responsible Party):
Ágnes Jermendy, Semmelweis University

Brief Summary:
This is a Phase I, open-label, single center trial to evaluate the feasibility and safety of low concentration CO2 gas mixture (5% CO2 + 95% air) inhalation in asphyxiated, cooled, mechanically ventilated newborns at risk of hypocapnia with The hypothesis is that hypocapnia, which is driven by hyperventilation in the presence of metabolic acidosis, is deleterious to the injured brain and can be safely avoided with low concentration CO2 inhalation.

Condition or disease Intervention/treatment Phase
Hypoxic-Ischaemic Encephalopathy Perinatal Asphyxia Hypocapnia Other: 5% carbon-dioxide inhalation Phase 1

Detailed Description:

Specific aims:

  1. To test the feasibility of low concentration inhalative CO2 gas mixture (5% CO2 + 95% air) administration to achieve a desired range of pCO2 of 40-60 mmHg in asphyxiated, cooled, mechanically ventilated newborns at risk of hypocapnia with moderate to severe hypoxic-ischemic encephalopathy.
  2. To test the safety of CO2 gas mixture (5% CO2 + 95% air) inhalation in asphyxiated, cooled, mechanically ventilated newborns at risk of hypocapnia with moderate to severe hypoxic-ischemic encephalopathy.

Term infants (≥ 36 weeks of gestation) will have to be at risk of hypocapnia to be eligible, as defined by a temperature corrected pCO2 ≤ 40 mmHg in blood gas analysis, at any time within six hours of life.

The gas mixture will be administered through patient circuits in conventional ventilators. Administered CO2 level will be closely monitored at the inhalation circuit (constant 5% = 36 mmHg). Blood gas samples will be taken hourly to ensure targeted and tolerable pCO2 levels.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Hypoxic-Ischemic Encephalopathy Therapy Optimization for Better Neuroprotection With Inhalative CO2 in Asphyxiated, Cooled, Mechanically Ventilated Neonates at Risk for Hypocapnia
Study Start Date : February 2016
Estimated Primary Completion Date : September 2017
Estimated Study Completion Date : February 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 5% carbon-dioxide inhalation
5% carbon-dioxide will be administered through patient circuits to asphyxiated, cooled, mechanically ventilated newborns at risk for hypocapnia
Other: 5% carbon-dioxide inhalation
5% CO2 (36 mmHg) and 95% air gas mixture inhalation, for a maximum of 12 hours or until metabolic acidosis recovery occurs as measured by BE > -5 mmol/L in arterial blood gas samples
Other Name: N-Carbogen




Primary Outcome Measures :
  1. Percentage of time spent in the desired pCO2 range of 40-60 mmHg (temp. corrected) during CO2 inhalation. [ Time Frame: 3 days ]

Secondary Outcome Measures :
  1. Number of seizures, either detected clinically or by amplitude integrated EEG monitoring [ Time Frame: Within one week ]
  2. Time until the end point of metabolic acidosis (BE > -5 mmol/L) [ Time Frame: During CO2 inhalation (max. 12 hours) ]
  3. Time until the end point of acidosis (pH > 7.25) [ Time Frame: During therapeutic hypothermia (max. 72 hours) ]
  4. Severe hypotension (mean arterial pressure less than 25 mmHg), despite full inotrope support and volume replacement. [ Time Frame: During therapeutic hypothermia (max. 72 hours) ]
  5. Intracranial haemorrhage detected by MRI [ Time Frame: Within seven days ]
  6. Reduction in Lac/NAA ratio on magnetic resonance spectroscopy [ Time Frame: Within seven days ]
  7. Preserved fractional anisotropy measured on diffusion weighted MRI [ Time Frame: Within seven days ]
  8. Death [ Time Frame: Within one month ]


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Ages Eligible for Study:   up to 6 Hours   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • At any time within six hours of life the temperature corrected pCO2 is less than or equal to 40 mmHg after the parameters of mechanical ventilation is set according to standard protocol (SIMV+VG 5ml/kg, fr 20/min, PEEP 5 H20cm, Ti 0,35-0,45 sec).
  • Moderate hypoxic- ischaemic encephalopathy, fulfilling TOBY criteria (A, B, C).
  • ≥ 36. gest. week
  • < 6th hours of life
  • Hypothermia treatment
  • Parental consent form
  • Spontaneous breathing
  • Endotracheal intubation
  • AUC, VUC in place

Exclusion Criteria:

  • Major birth defect
  • Meconium aspiration syndrome
  • Need for combined catecholamine therapy
  • FiO2 > 40%
  • Htc < 35%
  • Acid-base status: pH < 6.8, lactate > 15mM
  • Excessive bicarbonate administration during initial stabilization (> 1mmol/kg)

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): NCT02700854


Contacts
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Contact: Enikő Szakmár, MD +36307488941 drszakmareniko@gmail.com
Contact: Ágnes Jermendy, MD, PhD, MPH +36204600798 jermendy@gmail.com

Locations
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Hungary
Semmelweis University, 1st Department of Pediatrics Recruiting
Budapest, Hungary, 1085
Contact: Viktória Ollé    +36 (1) 3343186 x 52620    titkarsag.gyer1@med.semmelweis-univ.hu   
Sponsors and Collaborators
Semmelweis University
Investigators
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Study Director: Miklós Szabó, MD, PhD Semmelweis University, 1st Department of Pediatrics

Publications:
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Responsible Party: Ágnes Jermendy, assistant lecturer, Semmelweis University
ClinicalTrials.gov Identifier: NCT02700854     History of Changes
Other Study ID Numbers: 1Ped-AsphHENRIC001
First Posted: March 7, 2016    Key Record Dates
Last Update Posted: March 17, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Ágnes Jermendy, Semmelweis University:
Hypothermia treatment
Hypocapnia
Inhaled CO2
Neuroprotection

Additional relevant MeSH terms:
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Ischemia
Brain Diseases
Hypoxia
Brain Ischemia
Hypoxia-Ischemia, Brain
Asphyxia
Hypocapnia
Pathologic Processes
Central Nervous System Diseases
Nervous System Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Cerebrovascular Disorders
Vascular Diseases
Cardiovascular Diseases
Hypoxia, Brain
Death
Wounds and Injuries