Hydrocortisone Treatment In Systemic Low Blood Pressure During Hypothermia in Asphyxiated Newborns

• Status: Active, not recruiting
• Trial end date: 2022-02-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a prospective, randomized, double-blind, placebo controlled, single center study to compare low dose hydrocortisone vs placebo in systemic low blood pressure during hypothermia treatment in asphyxiated newborns. Patients will be allocated to one of the treatment arms (hydrocortisone or placebo) while receiving conventional inotropic therapy as needed.

The hypothesis is that cooled asphyxiated neonates develop relative adrenal insufficiency that may contribute to hypotension and lower efficacy of inotropic therapy in this patient population. Thus, the investigators are planning to measure initial serum cortisol levels and investigate the cardiovascular effects of low dose hydrocortisone supplementation besides conventional inotropic therapy in a placebo-controlled fashion.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Semmelweis University
• Treatments: Cortisol succinate; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate

Criteria

Inclusion Criteria:

1. The infant will be assessed sequentially by criteria A, B and C, as described by the TOBY trial and listed below, to be eligible for hypothermia treatment.

A. Infants ≥ 36 completed weeks of gestation admitted to the NICU with at least one of the following:

• Apgar score of ≤ 5 at 10 minutes after birth

• Continued need for resuscitation, including endotracheal or mask ventilation, at 10 minutes after birth

• Acidosis within 60 minutes of birth (defined as any occurrence of umbilical cord, arterial or capillary pH < 7.00)

• Base Deficit ≥ 16 mmol/L in umbilical cord or any blood sample (arterial, venous or capillary) within 60 minutes of birth

B. Moderate to severe encephalopathy, consisting of altered state of consciousness (lethargy, stupor or coma) AND at least one of the following:

• hypotonia

• abnormal reflexes including oculomotor or pupillary abnormalities

• absent or weak suck

• clinical seizures

C. At least 30 minutes duration of aEEG recording that shows abnormal background aEEG activity or seizures. There must be one of the following:

• normal background with some seizure activity

• moderately abnormal activity

• suppressed activity

• continuous seizure activity

2. Invasive arterial blood pressure measurement: umbilical arterial catheter or peripheral arterial catheter to measure invasively the arterial blood pressure.

3. During hypothermia treatment low blood pressure was detected and treated with the following:

• fluid therapy: 10-20 ml/kg isotonic NaCl if hypotension is still present

• inotropic therapy: dopamine in parallel with study intervention

4. A written informed consent has been obtained from a parent of each infant after explanation of the study.

Exclusion Criteria:

1. Signed informed consent is unavailable.

2. Infants who are expected to be > 6 hours of age (not suitable for cooling).

3. Congenital abnormalities, cardiac anomalies, meconium aspiration syndrome.

4. Low blood pressure coincides with high heart rate (>120/min) in cooled infants, suggesting hypovolaemia.

5. Haematocrit level < 35%.

6. Need for combined, ≥2 types of inotropic therapy.