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

NCT ID: NCT02700854

Last Updated: 2021-04-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2019-11-30

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 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.

Conditions

Hypoxic-Ischaemic Encephalopathy; Perinatal Asphyxia; Hypocapnia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

5% carbon-dioxide inhalation

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

Group Type: EXPERIMENTAL

5% carbon-dioxide inhalation

Intervention Type: OTHER

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

Interventions

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

Intervention Type: OTHER

Other Intervention Names

N-Carbogen

Eligibility 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)

• Maximum Eligible Age: 6 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Semmelweis University

OTHER

Sponsor Role: lead

Responsible Party

Ágnes Jermendy

assistant lecturer

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Miklós Szabó, MD, PhD

Role: STUDY_DIRECTOR

Semmelweis University, 1st Department of Pediatrics

Locations

Semmelweis University, 1st Department of Pediatrics

Budapest, , Hungary

Countries

Hungary

References

Laffey JG, Kavanagh BP. Hypocapnia. N Engl J Med. 2002 Jul 4;347(1):43-53. doi: 10.1056/NEJMra012457. No abstract available.

Reference Type: BACKGROUND

PMID: 12097540 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21146184 (View on PubMed)

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. doi: 10.1136/adc.2003.048785.

Reference Type: BACKGROUND

PMID: 15613575 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19797281 (View on PubMed)

Other Identifiers

1Ped-AsphHENRIC001

Identifier Type: -

Identifier Source: org_study_id