HENRIC: Hypoxic-Ischemic Encephalopathy Therapy Optimization in Neonates for Better Neuroprotection With Inhalative CO2
Study Details
Study Description
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 |
|---|---|---|
|
Phase 1 |
Detailed Description
Specific aims:
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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.
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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.
Study Design
Arms and Interventions
| 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 Names:
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Outcome Measures
Primary Outcome Measures
- Percentage of time spent in the desired pCO2 range of 40-60 mmHg (temp. corrected) during CO2 inhalation. [3 days]
Secondary Outcome Measures
- Number of seizures, either detected clinically or by amplitude integrated EEG monitoring [Within one week]
- Time until the end point of metabolic acidosis (BE > -5 mmol/L) [During CO2 inhalation (max. 12 hours)]
- Time until the end point of acidosis (pH > 7.25) [During therapeutic hypothermia (max. 72 hours)]
- Severe hypotension (mean arterial pressure less than 25 mmHg), despite full inotrope support and volume replacement. [During therapeutic hypothermia (max. 72 hours)]
- Intracranial haemorrhage detected by MRI [Within seven days]
- Reduction in Lac/NAA ratio on magnetic resonance spectroscopy [Within seven days]
- Preserved fractional anisotropy measured on diffusion weighted MRI [Within seven days]
- Death [Within one month]
Eligibility Criteria
Criteria
Inclusion Criteria:
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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).
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Moderate hypoxic- ischaemic encephalopathy, fulfilling TOBY criteria (A, B, C).
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≥ 36. gest. week
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< 6th hours of life
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Hypothermia treatment
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Parental consent form
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Spontaneous breathing
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Endotracheal intubation
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AUC, VUC in place
Exclusion Criteria:
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Major birth defect
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Meconium aspiration syndrome
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Need for combined catecholamine therapy
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FiO2 > 40%
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Htc < 35%
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Acid-base status: pH < 6.8, lactate > 15mM
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Excessive bicarbonate administration during initial stabilization (> 1mmol/kg)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Semmelweis University, 1st Department of Pediatrics | Budapest | Hungary | 1085 |
Sponsors and Collaborators
- Semmelweis University
Investigators
- Study Director: Miklós Szabó, MD, PhD, Semmelweis University, 1st Department of Pediatrics
Study Documents (Full-Text)
None provided.More Information
Publications
- Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, Kapellou O, Levene M, Marlow N, Porter E, Thoresen M, Whitelaw A, Brocklehurst P; TOBY Study Group. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med. 2009 Oct 1;361(14):1349-58. doi: 10.1056/NEJMoa0900854. Erratum in: N Engl J Med. 2010 Mar 18;362(11):1056.
- Klinger G, Beyene J, Shah P, Perlman M. Do hyperoxaemia and hypocapnia add to the risk of brain injury after intrapartum asphyxia? Arch Dis Child Fetal Neonatal Ed. 2005 Jan;90(1):F49-52.
- Laffey JG, Kavanagh BP. Hypocapnia. N Engl J Med. 2002 Jul 4;347(1):43-53. Review.
- Pappas A, Shankaran S, Laptook AR, Langer JC, Bara R, Ehrenkranz RA, Goldberg RN, Das A, Higgins RD, Tyson JE, Walsh MC; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Hypocarbia and adverse outcome in neonatal hypoxic-ischemic encephalopathy. J Pediatr. 2011 May;158(5):752-758.e1. doi: 10.1016/j.jpeds.2010.10.019. Epub 2010 Dec 10.
- 1Ped-AsphHENRIC001