UniCort: Hydrocortisone Therapy Optimization During Hypothermia Treatment in Asphyxiated Neonates

Sponsor

Semmelweis University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05836610

Collaborator

(none)

Enrollment

Location

Arms

71.3

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hypoxic-Ischemic Encephalopathy Asphyxia Hypotension Circulatory Failure Neonatal	Drug: Hydrocortisone	Phase 4

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

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention 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.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)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 21, 2021

Anticipated Primary Completion Date :

Sep 1, 2025

Anticipated Study Completion Date :

Sep 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Standard dose hydrocortisone The standard dose of hydrocortisone therapy in neonates for hypotension is 0.5 mg/kg every 6 hours.	Drug: Hydrocortisone intravenous bolus hydrocortisone therapy during hypothermia treatment Other Names: Solu-Cortef
Active Comparator: Modified dose hydrocortisone The modified dose of hydrocortisone therapy will be determined based on the pharmacokinetic results.	Drug: Hydrocortisone intravenous bolus hydrocortisone therapy during hypothermia treatment Other Names: Solu-Cortef

Arm

Intervention/Treatment

Active Comparator: Standard dose hydrocortisone

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

Drug: Hydrocortisone

intravenous bolus hydrocortisone therapy during hypothermia treatment

Other Names:

Solu-Cortef

Active Comparator: Modified dose hydrocortisone

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

Drug: Hydrocortisone

intravenous bolus hydrocortisone therapy during hypothermia treatment

Other Names:

Solu-Cortef

Outcome Measures

Primary Outcome Measures

Mean blood pressure increase [2 hours]
5 mmHg increase in mean arterial blood pressure after drug administration

Secondary Outcome Measures

Cardiovascular management [72 hours]
Length, cumulative and peak dose of inotrope treatment
Presence of relative adrenal insufficiency at baseline [Before hydrocortisone administration within max. 72 hours]
Low serum cortisol level at baseline
MRI outcome [4-10 days]
Brain injury on MRI examinations
Long term neurodevelopmental outcome [18-42 month]
Performance on motor and mental scales of Bayley III scales of infant development

Other Outcome Measures

Multiorgan failure [72 hours]
Presence of multiorgan failure during hypothermia

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 72 Hours

Sexes Eligible for Study:

All

Accepts 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