Hypoxic-Ischemic EncephalopathyPhase 4UniCortNCT05836610
Hydrocortisone Therapy Optimization During Hypothermia Treatment in Asphyxiated Neonates
A Phase 4 study testing Hydrocortisone in people with Hypoxic-Ischemic Encephalopathy and Asphyxia, run by Semmelweis University at 1 site in Hungary.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 72 hours
- Conditions the study is for
- Hypoxic-Ischemic Encephalopathy, Asphyxia, Hypotension
- What is being tested?
- Hydrocortisone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteHungary
- Study dates
- 21 Sep 2021to Sep 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 72 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- infants who are expected to be > 6 hours of age (not suitable for cooling)
- critical congenital abnormalities
- genetic disease
- signed informed consent is unavailable
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Hungary1 site, 1 recruiting
- Recruiting
Semmelweis University Department of Pediatrics (Bókay street Unit)
Budapest, Pest County, 1083
Ollé Viktória, titkarsag.gyer1@med.semmelweis-univ.hu
About this study
Official title: Hydrocortisone Therapy Optimization During Hypothermia Treatment in Asphyxiated Neonates - a Pharmacokinetic Study
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.
Read the 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.
- Being tested
- Hydrocortisone
- Keywords
- Hypothermia treatment, Relative adrenal insufficiency, Hydrocortisone supplementation, Hydrocortisone pharmacokinetics, Hypoxic-Ischemic Encephalopathy, Asphyxia
- Medical subject headings
- Hypoxia-Ischemia, Brain, Asphyxia, Hypotension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydrocortisoneDrug
Also called Solu-Cortef
intravenous bolus hydrocortisone therapy during hypothermia treatment
| Study group | Role | What they receive |
|---|---|---|
| Standard dose hydrocortisone | Active comparator | The standard dose of hydrocortisone therapy in neonates for hypotension is 0.5 mg/kg every 6 hours. Receives: Drug: Hydrocortisone |
| Modified dose hydrocortisone | Active comparator | The modified dose of hydrocortisone therapy will be determined based on the pharmacokinetic results. Receives: Drug: Hydrocortisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean blood pressure increase
5 mmHg increase in mean arterial blood pressure after drug administration
Measured: 2 hours
Secondary outcomes (4)
Cardiovascular management
Length, cumulative and peak dose of inotrope treatment
Measured: 72 hours
Presence of relative adrenal insufficiency at baseline
Low serum cortisol level at baseline
Measured: Before hydrocortisone administration within max. 72 hours
MRI outcome
Brain injury on MRI examinations
Measured: 4-10 days
Long term neurodevelopmental outcome
Performance on motor and mental scales of Bayley III scales of infant development
Measured: 18-42 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2023
- Study start21 Sep 2021
- Primary completionSep 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Hypoxic-Ischemic 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- 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)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Semmelweis University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kata Kovacs, Semmelweis University
- Investigators
- Kata Kovacs, MD, PhD, Principal investigator, Semmelweis UniversityMiklós Szabó, MD, PhD, Study director, Semmelweis University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05836610
- Sponsor's protocol ID
- SU-Ped-AsphCort 002
- Acronym
- UniCort
- Status last verified
- Apr 2026
- First submitted
- 19 Apr 2023
- Last updated
- 28 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 19797281Kovacs 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.
PubMed 31155392Kovacs 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.
PubMed 29626704Watterberg 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.
PubMed 27156187Concepcion 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.
PubMed 29778695Sarkar 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.
PubMed 20227357
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hydrocortisone Therapy Optimization During Hypothermia Treatment in Asphyxiated Neonates - a Pharmacokinetic Study
- ClinicalTrials.gov ID
- NCT05836610
- Acronym / sponsor ID
- UniCort / SU-Ped-AsphCort 002
- Keywords
- Hypothermia treatment, Relative adrenal insufficiency, Hydrocortisone supplementation, Hydrocortisone pharmacokinetics, Hypoxic-Ischemic Encephalopathy, Asphyxia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Semmelweis UniversityUniversity, hospital or other
- Study start
- 21 Sep 2021 (actual)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 1 May 2023 (actual)
- 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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Standard dose hydrocortisone | Active comparator | Drug: HydrocortisoneThe standard dose of hydrocortisone therapy in neonates for hypotension is 0.5 mg/kg every 6 hours. |
| Modified dose hydrocortisone | Active comparator | Drug: HydrocortisoneThe modified dose of hydrocortisone therapy will be determined based on the pharmacokinetic results. |
Who may qualify
- Ages
- Up to 72 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (4 listed)
- infants who are expected to be > 6 hours of age (not suitable for cooling)
- critical congenital abnormalities
- genetic disease
- signed informed consent is unavailable
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 |
|---|---|---|
| HydrocortisoneAlso: Solu-Cortefintravenous bolus hydrocortisone therapy during hypothermia treatment | Drug | Modified dose hydrocortisone, Standard dose hydrocortisone |
Primary outcome
Mean blood pressure increase
Time frame: 2 hours
5 mmHg increase in mean arterial blood pressure after drug administration
4 secondary outcomes
Cardiovascular management
Time frame: 72 hours
Presence of relative adrenal insufficiency at baseline
Time frame: Before hydrocortisone administration within max. 72 hours
MRI outcome
Time frame: 4-10 days
Long term neurodevelopmental outcome
Time frame: 18-42 month
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2026.
- 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.
- Background: PubMed 31155392Kovacs 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.
- Background: PubMed 29626704Kovacs 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.
- Background: PubMed 27156187Watterberg 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.
- Background: PubMed 29778695Concepcion 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.
- Background: PubMed 20227357Sarkar 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.
- 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.
Kata Kovacs, MD, PhD principal investigator
Semmelweis University
Miklós Szabó, MD, PhD study director
Semmelweis University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Hydrocortisone in people with Hypoxic-Ischemic Encephalopathy and 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 6 inclusion and 4 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: looking for participants now, as of the sponsor's last update on 28 Apr 2026. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dobi Marianna, MD (+36303357529, mariannadobi@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean blood pressure increase (time frame: 2 hours). 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 NCT05836610, which also lists 6 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 28 Apr 2026.