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

Semmelweis University

Status and phase: Enrolling; Phase 4

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

Treatments: Drug: Hydrocortisone

Study type: Interventional

Funder types: Other

Identifiers

NCT05836610

SU-Ped-AsphCort 002

Details and patient eligibility

About

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.

Full 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.

Enrollment: 50 estimated patients

Sex: All

Ages: Under 72 hours old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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50 participants in 2 patient groups

Standard dose hydrocortisone

Active Comparator group

Description:

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

Treatment:

Drug: Hydrocortisone

Modified dose hydrocortisone

Active Comparator group

Description:

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

Treatment:

Drug: Hydrocortisone