Clinical Trial: Hypoxic-Ischemic Encephalopathy Therapy Optimization in Neonates for Better Neuroprotection With Inhalative CO2

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Hypoxic-Ischemic Encephalopathy Therapy Optimization for Better Neuroprotection With Inhalative CO2 in Asphyxiated, Cooled, Mechanically Ventilated Neonates at Risk for Hypocapni

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.

Detailed Summary:

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.


Sponsor: Semmelweis University

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

Original Primary Outcome: Same as current

Current Secondary Outcome:

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


Original Secondary Outcome: Same as current

Information By: Semmelweis University

Dates:
Date Received: February 24, 2016
Date Started: February 2016
Date Completion: February 2020
Last Updated: March 16, 2017
Last Verified: March 2017