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

Semmelweis University

Status and phase: Completed; Phase 1

Conditions: Perinatal Asphyxia; Hypocapnia; Hypoxic-Ischaemic Encephalopathy

Treatments: Other: 5% carbon-dioxide inhalation

Study type: Interventional

Funder types: Other

Identifiers

NCT02700854

1Ped-AsphHENRIC001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 10 patients

Sex: All

Ages: Under 6 hours old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 1 patient group

5% carbon-dioxide inhalation

Experimental group

Description:

5% carbon-dioxide will be administered through patient circuits to asphyxiated, cooled, mechanically ventilated newborns at risk for hypocapnia

Treatment:

Other: 5% carbon-dioxide inhalation