Hydrocortisone Therapy Optimization During Hypothermia Treatment in Asphyxiated Neonates

Hypotension Clinical Trial

— UniCort  

Official title:

Hydrocortisone Therapy Optimization During Hypothermia Treatment in Asphyxiated Neonates - a Pharmacokinetic Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05836610
• Other study ID #: SU-Ped-AsphCort 002
• Status: Recruiting
• Phase: Phase 4
• Start date: September 21, 2021
• Est. completion date: September 2027

Study information

• Verified date: April 2023
• Source: Semmelweis University
• Contact: Dobi Marianna, MD
• Phone: +36303357529
• Email: mariannadobi[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: September 2027
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 72 Hours

Eligibility

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

Related Conditions & MeSH terms

• Asphyxia
• Brain Diseases
• Brain Ischemia
• Hypotension
• Hypothermia
• Hypoxia-Ischemia, Brain
• Hypoxic-Ischemic Encephalopathy
• Shock

Intervention

Drug:
• Hydrocortisone
intravenous bolus hydrocortisone therapy during hypothermia treatment

Locations

Country	Name	City	State
Hungary	Semmelweis University Department of Pediatrics (Bókay street Unit)	Budapest	Pest Megye

Sponsors (1)

Lead Sponsor	Collaborator
Semmelweis University

Country where clinical trial is conducted

Hungary, 

References & 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Multiorgan failure	Presence of multiorgan failure during hypothermia	72 hours
Primary	Mean blood pressure increase	5 mmHg increase in mean arterial blood pressure after drug administration	2 hours
Secondary	Cardiovascular management	Length, cumulative and peak dose of inotrope treatment	72 hours
Secondary	Presence of relative adrenal insufficiency at baseline	Low serum cortisol level at baseline	Before hydrocortisone administration within max. 72 hours
Secondary	MRI outcome	Brain injury on MRI examinations	4-10 days
Secondary	Long term neurodevelopmental outcome	Performance on motor and mental scales of Bayley III scales of infant development	18-42 month