Hydrocortisone Therapy Optimization During Hypothermia Treatment in Asphyxiated Neonates

NCT05836610 | Recruiting Phase 4

• 1 other identifier: SU-Ped-AsphCort 002
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypoxic-Ischemic Encephalopathy; Asphyxia; Hypotension; Circulatory Failure Neonatal

Keywords

Hypothermia treatment; Relative adrenal insufficiency; Hydrocortisone supplementation; Hydrocortisone pharmacokinetics; Hypoxic-Ischemic Encephalopathy; Asphyxia

Outcome Measures

Primary Outcomes (1)

• Mean blood pressure increase

  5 mmHg increase in mean arterial blood pressure after drug administration

  2 hours

Secondary Outcomes (4)

• Cardiovascular management

  72 hours

• Presence of relative adrenal insufficiency at baseline

  Before hydrocortisone administration within max. 72 hours

• MRI outcome

  4-10 days

• Long term neurodevelopmental outcome

  18-42 month

Other Outcomes (1)

• Multiorgan failure

  72 hours

Study Arms (2)

Standard dose hydrocortisone

ACTIVE COMPARATOR

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

Drug: Hydrocortisone

Modified dose hydrocortisone

ACTIVE COMPARATOR

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

Drug: Hydrocortisone

Interventions

Hydrocortisone DRUG

intravenous bolus hydrocortisone therapy during hypothermia treatment

Also known as: Solu-Cortef

Modified dose hydrocortisone; Standard dose hydrocortisone

Eligibility Criteria

• Age: Up to 72 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• infants who are expected to be \> 6 hours of age (not suitable for cooling)
• critical congenital abnormalities
• genetic disease
• signed informed consent is unavailable

Sponsors & Collaborators

• Semmelweis University: lead

Study Sites (1)

Semmelweis University Department of Pediatrics (Bókay street Unit)

Budapest, Pest County, 1083, Hungary

RECRUITING

Related Publications (6)

• 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.

  PMID: 19797281 BACKGROUND

• 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.

  PMID: 31155392 BACKGROUND

• 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.

  PMID: 29626704 BACKGROUND

• 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.

  PMID: 27156187 BACKGROUND

• 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.

  PMID: 29778695 BACKGROUND

• 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.

  PMID: 20227357 BACKGROUND

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain; Asphyxia; Hypotension

Interventions

Hydrocortisone; hydrocortisone hemisuccinate

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; Death; Pathologic Processes; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• Kata Kovacs, MD, PhD

  Semmelweis University

  PRINCIPAL INVESTIGATOR

• Miklós Szabó, MD, PhD

  Semmelweis University

  STUDY DIRECTOR

Central Study Contacts

Dobi Marianna, MD

CONTACT

+36303357529; mariannadobi@gmail.com

Kata Kovacs, MD, PhD

CONTACT

+36204969653; mail.kata.kovacs@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant lecturer

Model Details: 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.

Study Record Dates

• First Submitted: April 19, 2023
• First Posted: May 1, 2023
• Study Start: September 21, 2021
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1)