Hydrocortisone Therapy Optimization During Hypothermia Treatment in Asphyxiated Neonates

NCT ID: NCT05836610

Last Updated: 2023-05-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-21

Study Completion Date

2027-09-30

Brief Summary

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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

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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.

Conditions

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Hypoxic-Ischemic Encephalopathy Asphyxia Hypotension Circulatory Failure Neonatal

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Standard dose hydrocortisone

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

Group Type ACTIVE_COMPARATOR

Hydrocortisone

Intervention Type DRUG

intravenous bolus hydrocortisone therapy during hypothermia treatment

Modified dose hydrocortisone

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

Group Type ACTIVE_COMPARATOR

Hydrocortisone

Intervention Type DRUG

intravenous bolus hydrocortisone therapy during hypothermia treatment

Interventions

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Hydrocortisone

intravenous bolus hydrocortisone therapy during hypothermia treatment

Intervention Type DRUG

Other Intervention Names

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Solu-Cortef

Eligibility Criteria

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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
Maximum Eligible Age

72 Hours

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Semmelweis University

OTHER

Sponsor Role lead

Responsible Party

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Kata Kovacs

Assistant lecturer

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Kata Kovacs, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Semmelweis University

Miklós Szabó, MD, PhD

Role: STUDY_DIRECTOR

Semmelweis University

Locations

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Semmelweis University Department of Pediatrics (Bókay street Unit)

Budapest, Pest County, Hungary

Site Status RECRUITING

Countries

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Hungary

Central Contacts

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Dobi Marianna, MD

Role: CONTACT

+36303357529

Kata Kovacs, MD, PhD

Role: CONTACT

+36204969653

Facility Contacts

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Ollé Viktória

Role: primary

References

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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)

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.

Reference Type BACKGROUND
PMID: 31155392 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29626704 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27156187 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29778695 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20227357 (View on PubMed)

Other Identifiers

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SU-Ped-AsphCort 002

Identifier Type: -

Identifier Source: org_study_id

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