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Hydrocortisone Therapy Optimization During Hypothermia Treatment in Asphyxiated Neonates (UniCort)

Primary Purpose

Hypoxic-Ischemic Encephalopathy, Asphyxia, Hypotension

Status
Recruiting
Phase
Phase 4
Locations
Hungary
Study Type
Interventional
Intervention
Hydrocortisone
Sponsored by
Semmelweis University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypoxic-Ischemic Encephalopathy focused on measuring Hypothermia treatment, Relative adrenal insufficiency, Hydrocortisone supplementation, Hydrocortisone pharmacokinetics, Hypoxic-Ischemic Encephalopathy, Asphyxia

Eligibility Criteria

undefined - 72 Hours (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria: gestational age ≥ 36 weeks provision of whole-body hypothermia treatment (as described by Azzopardi et al.) presence of systemic hypotension (defined as a mean arterial pressure less than the gestational age in weeks) indication for hydrocortisone treatment during hypothermia by the attending physician indwelling arterial catheter to take blood samples without additional painful punctures: umbilical arterial catheter or peripheral arterial catheter written informed parental consent Exclusion Criteria: infants who are expected to be > 6 hours of age (not suitable for cooling) critical congenital abnormalities genetic disease signed informed consent is unavailable

Sites / Locations

  • Semmelweis University Department of Pediatrics (Bókay street Unit)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Standard dose hydrocortisone

Modified dose hydrocortisone

Arm Description

The standard dose of hydrocortisone therapy in neonates for hypotension is 0.5 mg/kg every 6 hours.

The modified dose of hydrocortisone therapy will be determined based on the pharmacokinetic results.

Outcomes

Primary Outcome Measures

Mean blood pressure increase
5 mmHg increase in mean arterial blood pressure after drug administration

Secondary Outcome Measures

Cardiovascular management
Length, cumulative and peak dose of inotrope treatment
Presence of relative adrenal insufficiency at baseline
Low serum cortisol level at baseline
MRI outcome
Brain injury on MRI examinations
Long term neurodevelopmental outcome
Performance on motor and mental scales of Bayley III scales of infant development

Full Information

First Posted
April 19, 2023
Last Updated
April 30, 2023
Sponsor
Semmelweis University
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1. Study Identification

Unique Protocol Identification Number
NCT05836610
Brief Title
Hydrocortisone Therapy Optimization During Hypothermia Treatment in Asphyxiated Neonates
Acronym
UniCort
Official Title
Hydrocortisone Therapy Optimization During Hypothermia Treatment in Asphyxiated Neonates - a Pharmacokinetic Study
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 21, 2021 (Actual)
Primary Completion Date
September 2025 (Anticipated)
Study Completion Date
September 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Semmelweis University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a prospective, single center, pharmacokinetic study of intravenous hydrocortisone therapy for systemic low blood pressure during hypothermia treatment in asphyxiated newborns. Patients will be allocated to hydrocortisone supplementation while receiving conventional inotropic therapy as needed. The hypothesis is that a detailed study of hydrocortisone pharmacokinetics during therapeutic hypothermia would help to personalize steroid supplementation in asphyxiated neonates. As the overall metabolic rate decreases with lower body temperature, drug metabolism is likely to be reduced as well, and lower doses, or less frequent dosing will be sufficient to achieve the targeted steroid range and biological effects in asphyxiated neonates with relative adrenal insufficiency. Thus, the investigators are planning to measure initial, baseline serum cortisol levels and serial serum cortisol levels after hydrocortisone supplementation in cooled asphyxiated neonates.
Detailed Description
The ultimate goal of the present study, is to describe a new approach of more personalized and safe care to infants with birth asphyxia and hemodynamic instability. Asphyxiated infants often present with multiorgan failure and low blood pressure. Therapeutic hypothermia, the standard of care, could worsen hemodynamic instability; therefore, treatment of cardiovascular impairment represents a major challenge in this clinical setting. An association was previously described between hypotension and low serum cortisol values in this patient population, and it was suggested that relative adrenal insufficiency (RAI) is an important factor in the circulatory compromise of these patients. In the "CORTISoL" clinical trial, it was also demonstrated that low-dose hydrocortisone therapy was effective in the treatment of cardiovascular impairment in asphyxiated neonates; however, some gaps remain in the knowledge on optimal dosing. Importantly, steroid therapy should be administered at the lowest effective dose and for the shortest possible duration in this vulnerable population. In the current pharmacokinetic study, the investigators propose a stepwise approach to more detailed understanding of RAI and hydrocortisone pharmacokinetics in asphyxiated neonates. The findings would certainly aid clinical decision-making and allow for more personalized therapeutic interventions for the treatment of hemodynamic instability.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypoxic-Ischemic Encephalopathy, Asphyxia, Hypotension, Circulatory Failure Neonatal
Keywords
Hypothermia treatment, Relative adrenal insufficiency, Hydrocortisone supplementation, Hydrocortisone pharmacokinetics, Hypoxic-Ischemic Encephalopathy, Asphyxia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Sequential Assignment
Model Description
Pharmacokinetic analysis of the standard dose hydrocortisone therapy (0.5 mg/kg/6 hours) during hypothermia treatment, then compare the effects of the modified dose hydrocortisone therapy which will be determined based on the pharmacokinetic results.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Standard dose hydrocortisone
Arm Type
Active Comparator
Arm Description
The standard dose of hydrocortisone therapy in neonates for hypotension is 0.5 mg/kg every 6 hours.
Arm Title
Modified dose hydrocortisone
Arm Type
Active Comparator
Arm Description
The modified dose of hydrocortisone therapy will be determined based on the pharmacokinetic results.
Intervention Type
Drug
Intervention Name(s)
Hydrocortisone
Other Intervention Name(s)
Solu-Cortef
Intervention Description
intravenous bolus hydrocortisone therapy during hypothermia treatment
Primary Outcome Measure Information:
Title
Mean blood pressure increase
Description
5 mmHg increase in mean arterial blood pressure after drug administration
Time Frame
2 hours
Secondary Outcome Measure Information:
Title
Cardiovascular management
Description
Length, cumulative and peak dose of inotrope treatment
Time Frame
72 hours
Title
Presence of relative adrenal insufficiency at baseline
Description
Low serum cortisol level at baseline
Time Frame
Before hydrocortisone administration within max. 72 hours
Title
MRI outcome
Description
Brain injury on MRI examinations
Time Frame
4-10 days
Title
Long term neurodevelopmental outcome
Description
Performance on motor and mental scales of Bayley III scales of infant development
Time Frame
18-42 month
Other Pre-specified Outcome Measures:
Title
Multiorgan failure
Description
Presence of multiorgan failure during hypothermia
Time Frame
72 hours

10. Eligibility

Sex
All
Maximum Age & Unit of Time
72 Hours
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: gestational age ≥ 36 weeks provision of whole-body hypothermia treatment (as described by Azzopardi et al.) presence of systemic hypotension (defined as a mean arterial pressure less than the gestational age in weeks) indication for hydrocortisone treatment during hypothermia by the attending physician indwelling arterial catheter to take blood samples without additional painful punctures: umbilical arterial catheter or peripheral arterial catheter written informed parental consent Exclusion Criteria: infants who are expected to be > 6 hours of age (not suitable for cooling) critical congenital abnormalities genetic disease signed informed consent is unavailable
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dobi Marianna, MD
Phone
+36303357529
Email
mariannadobi@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Kata Kovacs, MD, PhD
Phone
+36204969653
Email
mail.kata.kovacs@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kata Kovacs, MD, PhD
Organizational Affiliation
Semmelweis University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Miklós Szabó, MD, PhD
Organizational Affiliation
Semmelweis University
Official's Role
Study Director
Facility Information:
Facility Name
Semmelweis University Department of Pediatrics (Bókay street Unit)
City
Budapest
State/Province
Pest Megye
ZIP/Postal Code
1083
Country
Hungary
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ollé Viktória
Email
titkarsag.gyer1@med.semmelweis-univ.hu

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
19797281
Citation
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.
Results Reference
background
PubMed Identifier
31155392
Citation
Kovacs K, Szakmar E, Meder U, Szakacs L, Cseko A, Vatai B, Szabo AJ, McNamara PJ, Szabo M, Jermendy A. A Randomized Controlled Study of Low-Dose Hydrocortisone Versus Placebo in Dopamine-Treated Hypotensive Neonates Undergoing Hypothermia Treatment for Hypoxic-Ischemic Encephalopathy. J Pediatr. 2019 Aug;211:13-19.e3. doi: 10.1016/j.jpeds.2019.04.008. Epub 2019 May 30.
Results Reference
background
PubMed Identifier
29626704
Citation
Kovacs K, Szakmar E, Meder U, Cseko A, Szabo AJ, Szabo M, Jermendy A. Serum cortisol levels in asphyxiated infants with hypotension. Early Hum Dev. 2018 May;120:40-45. doi: 10.1016/j.earlhumdev.2018.03.003. Epub 2018 Apr 4. No abstract available.
Results Reference
background
PubMed Identifier
27156187
Citation
Watterberg KL. Hydrocortisone Dosing for Hypotension in Newborn Infants: Less Is More. J Pediatr. 2016 Jul;174:23-26.e1. doi: 10.1016/j.jpeds.2016.04.005. Epub 2016 May 4. No abstract available.
Results Reference
background
PubMed Identifier
29778695
Citation
Concepcion KR, Zhang L. Corticosteroids and perinatal hypoxic-ischemic brain injury. Drug Discov Today. 2018 Oct;23(10):1718-1732. doi: 10.1016/j.drudis.2018.05.019. Epub 2018 May 17.
Results Reference
background
PubMed Identifier
20227357
Citation
Sarkar S, Barks JD. Systemic complications and hypothermia. Semin Fetal Neonatal Med. 2010 Oct;15(5):270-5. doi: 10.1016/j.siny.2010.02.001. Epub 2010 Mar 12.
Results Reference
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Hydrocortisone Therapy Optimization During Hypothermia Treatment in Asphyxiated Neonates

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