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

Perinatal Asphyxia Clinical Trial

— HENRIC  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02700854
• Other study ID #: 1Ped-AsphHENRIC001
• Status: Completed
• Phase: Phase 1
• Start date: February 2016
• Est. completion date: November 2019

Study information

• Verified date: April 2021
• Source: Semmelweis University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: November 2019
• Est. primary completion date: September 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 6 Hours

Eligibility

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)

Related Conditions & MeSH terms

• Asphyxia
• Brain Diseases
• Brain Ischemia
• Hypocapnia
• Hypoxia
• Hypoxia-Ischemia, Brain
• Hypoxic-Ischaemic Encephalopathy
• Ischemia
• Perinatal Asphyxia

Intervention

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

Locations

Country	Name	City	State
Hungary	Semmelweis University, 1st Department of Pediatrics	Budapest

Sponsors (1)

Lead Sponsor	Collaborator
Semmelweis University

Country where clinical trial is conducted

Hungary, 

References & Publications (4)

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. — View Citation

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. — View Citation

Laffey JG, Kavanagh BP. Hypocapnia. N Engl J Med. 2002 Jul 4;347(1):43-53. Review. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of time spent in the desired pCO2 range of 40-60 mmHg (temp. corrected) during CO2 inhalation.		3 days
Secondary	Number of seizures, either detected clinically or by amplitude integrated EEG monitoring		Within one week
Secondary	Time until the end point of metabolic acidosis (BE > -5 mmol/L)		During CO2 inhalation (max. 12 hours)
Secondary	Time until the end point of acidosis (pH > 7.25)		During therapeutic hypothermia (max. 72 hours)
Secondary	Severe hypotension (mean arterial pressure less than 25 mmHg), despite full inotrope support and volume replacement.		During therapeutic hypothermia (max. 72 hours)
Secondary	Intracranial haemorrhage detected by MRI		Within seven days
Secondary	Reduction in Lac/NAA ratio on magnetic resonance spectroscopy		Within seven days
Secondary	Preserved fractional anisotropy measured on diffusion weighted MRI		Within seven days
Secondary	Death		Within one month