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

NCT02700854 | Completed Phase 1 DMC

• 1 other identifier: 1Ped-AsphHENRIC001
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypoxic-Ischaemic Encephalopathy; Perinatal Asphyxia; Hypocapnia

Keywords

Hypothermia treatment; Hypocapnia; Inhaled CO2; Neuroprotection

Outcome Measures

Primary Outcomes (1)

• Percentage of time spent in the desired pCO2 range of 40-60 mmHg (temp. corrected) during CO2 inhalation.

  3 days

Secondary Outcomes (8)

• 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

Study Arms (1)

5% carbon-dioxide inhalation

EXPERIMENTAL

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

Other: 5% carbon-dioxide inhalation

Interventions

5% carbon-dioxide inhalation 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

Also known as: N-Carbogen

5% carbon-dioxide inhalation

Eligibility Criteria

• Age: Up to 6 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Semmelweis University: lead

Study Sites (1)

Semmelweis University, 1st Department of Pediatrics

Budapest, 1085, Hungary

Location

Related Publications (4)

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

  PMID: 12097540 BACKGROUND

• 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.

  PMID: 21146184 BACKGROUND

• 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.

  PMID: 15613575 BACKGROUND

• 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.

  PMID: 19797281 BACKGROUND

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain; Hypocapnia

Condition Hierarchy (Ancestors)

Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Miklós Szabó, MD, PhD

  Semmelweis University, 1st Department of Pediatrics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: assistant lecturer

Study Record Dates

• First Submitted: February 24, 2016
• First Posted: March 7, 2016
• Study Start: February 1, 2016
• Primary Completion: September 1, 2019
• Study Completion: November 1, 2019
• Last Updated: April 26, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1)