Hypoxic-Ischaemic EncephalopathyPhase 1HENRICNCT02700854
Hypoxic-Ischemic Encephalopathy Therapy Optimization in Neonates for Better Neuroprotection With Inhalative CO2
A Phase 1 study testing 5% carbon-dioxide inhalation in people with Hypoxic-Ischaemic Encephalopathy and Perinatal Asphyxia, run by Semmelweis University at 1 site in Hungary.
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… Read more about this study
- Who is it for?
- Ages Up to 6 hours
- Conditions the study is for
- Hypoxic-Ischaemic Encephalopathy, Perinatal Asphyxia, Hypocapnia
- What is being tested?
- 5% carbon-dioxide inhalation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteHungary
- Study dates
- Feb 2016to Nov 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 6 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Show all 9Show fewer
- Spontaneous breathing
- Endotracheal intubation
- AUC, VUC in place
Who cannot join
- 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 locations and contacts
1 site in 1 country.
Hungary1 site
Semmelweis University, 1st Department of Pediatrics
Budapest, 1085
About this study
Official title: Hypoxic-Ischemic Encephalopathy Therapy Optimization for Better Neuroprotection With Inhalative CO2 in Asphyxiated, Cooled, Mechanically Ventilated Neonates at Risk for Hypocapnia
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.
Read the detailed description
Specific aims:
- 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.
- 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.
- Being tested
- 5% carbon-dioxide inhalation
- Keywords
- Hypothermia treatment, Hypocapnia, Inhaled CO2, Neuroprotection
- Medical subject headings
- Hypoxia-Ischemia, Brain, Hypocapnia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5% carbon-dioxide inhalationOther
Also called N-Carbogen
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
| Study group | Role | What they receive |
|---|---|---|
| 5% carbon-dioxide inhalation | Experimental | 5% carbon-dioxide will be administered through patient circuits to asphyxiated, cooled, mechanically ventilated newborns at risk for hypocapnia Receives: Other: 5% carbon-dioxide inhalation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of time spent in the desired pCO2 range of 40-60 mmHg (temp. corrected) during CO2 inhalation.
Measured: 3 days
Secondary outcomes (8)
Number of seizures, either detected clinically or by amplitude integrated EEG monitoring
Measured: Within one week
Time until the end point of metabolic acidosis (BE > -5 mmol/L)
Measured: During CO2 inhalation (max. 12 hours)
Time until the end point of acidosis (pH > 7.25)
Measured: During therapeutic hypothermia (max. 72 hours)
Severe hypotension (mean arterial pressure less than 25 mmHg), despite full inotrope support and volume replacement.
Measured: During therapeutic hypothermia (max. 72 hours)
Intracranial haemorrhage detected by MRI
Measured: Within seven days
Reduction in Lac/NAA ratio on magnetic resonance spectroscopy
Measured: Within seven days
Preserved fractional anisotropy measured on diffusion weighted MRI
Measured: Within seven days
Death
Measured: Within one month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2016 (estimated)
- Study startFeb 2016
- Primary completionSep 2019
- Study completionNov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Hypoxic-Ischaemic EncephalopathyStudies of the same condition, open and under way.
- More trials run by Semmelweis UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Semmelweis University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ágnes Jermendy, Semmelweis University
- Investigators
- Miklós Szabó, MD, PhD, Study director, Semmelweis University, 1st Department of Pediatrics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02700854
- Sponsor's protocol ID
- 1Ped-AsphHENRIC001
- Acronym
- HENRIC
- Status last verified
- Apr 2021
- First submitted
- 24 Feb 2016
- Last updated
- 26 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Laffey JG, Kavanagh BP. Hypocapnia. N Engl J Med. 2002 Jul 4;347(1):43-53. doi: 10.1056/NEJMra012457. No abstract available.
PubMed 12097540Pappas 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.
PubMed 21146184Klinger 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.
PubMed 15613575Azzopardi 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.
PubMed 19797281
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hypoxic-Ischemic Encephalopathy Therapy Optimization for Better Neuroprotection With Inhalative CO2 in Asphyxiated, Cooled, Mechanically Ventilated Neonates at Risk for Hypocapnia
- ClinicalTrials.gov ID
- NCT02700854
- Acronym / sponsor ID
- HENRIC / 1Ped-AsphHENRIC001
- Keywords
- Hypothermia treatment, Hypocapnia, Inhaled CO2, Neuroprotection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Semmelweis UniversityUniversity, hospital or other
- Study start
- Feb 2016
- Primary completion
- Sep 2019 (actual)
- Study completion
- Nov 2019 (actual)
- First posted
- 7 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 5% carbon-dioxide inhalation | Experimental | Other: 5% carbon-dioxide inhalation5% carbon-dioxide will be administered through patient circuits to asphyxiated, cooled, mechanically ventilated newborns at risk for hypocapnia |
Who may qualify
- Ages
- Up to 6 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (7 listed)
- Major birth defect
- Meconium aspiration syndrome
- Need for combined catecholamine therapy
- FiO2 > 40%
- Htc < 35%
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 5% carbon-dioxide inhalationAlso: N-Carbogen5% 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 | 5% carbon-dioxide inhalation |
Primary outcome
Percentage of time spent in the desired pCO2 range of 40-60 mmHg (temp. corrected) during CO2 inhalation.
Time frame: 3 days
8 secondary outcomes
Number of seizures, either detected clinically or by amplitude integrated EEG monitoring
Time frame: Within one week
Time until the end point of metabolic acidosis (BE > -5 mmol/L)
Time frame: During CO2 inhalation (max. 12 hours)
Time until the end point of acidosis (pH > 7.25)
Time frame: During therapeutic hypothermia (max. 72 hours)
Severe hypotension (mean arterial pressure less than 25 mmHg), despite full inotrope support and volume replacement.
Time frame: During therapeutic hypothermia (max. 72 hours)
Intracranial haemorrhage detected by MRI
Time frame: Within seven days
Reduction in Lac/NAA ratio on magnetic resonance spectroscopy
Time frame: Within seven days
Preserved fractional anisotropy measured on diffusion weighted MRI
Time frame: Within seven days
Death
Time frame: Within one month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2021.
- Background: PubMed 12097540Laffey JG, Kavanagh BP. Hypocapnia. N Engl J Med. 2002 Jul 4;347(1):43-53. doi: 10.1056/NEJMra012457. No abstract available.
- Background: PubMed 21146184Pappas 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.
- Background: PubMed 15613575Klinger 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.
- Background: PubMed 19797281Azzopardi 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Miklós Szabó, MD, PhD study director
Semmelweis University, 1st Department of Pediatrics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 5% carbon-dioxide inhalation in people with Hypoxic-Ischaemic Encephalopathy and Perinatal Asphyxia, run by Semmelweis University at 1 site in Hungary.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hungary. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of time spent in the desired pCO2 range of 40-60 mmHg (temp. corrected) during CO2 inhalation. (time frame: 3 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02700854, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2021.