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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02700854
Other study ID # 1Ped-AsphHENRIC001
Secondary ID
Status Completed
Phase Phase 1
First received
Last updated
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
Health authority
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)

Study Design


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
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