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

NCT02700828 | Completed Phase 2

• 1 other identifier: 1Ped-AsphCort 001
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hypoxic-Ischemic Encephalopathy; Asphyxia

Keywords

Hypothermia treatment; Circulatory failure; Neonatal hypotension; Relative adrenal insufficiency; Hydrocortisone supplementation

Outcome Measures

Primary Outcomes (1)

• Compare mean arterial blood pressure (MAP) change in the patients receiving hydrocortisone vs placebo

  Circulatory stability as measured by an increased MAP (5 mmHg) within two hours after drug administration

  2 hours

Secondary Outcomes (6)

• Frequency of initially low serum cortisol in hypotensive asphyxiated newborns undergoing therapeutic hypothermia

  before hydrocortisone administration within max. 72 hours

• Length of dopamine treatment in the patients receiving hydrocortisone vs placebo

  72 hours

• Cumulative dopamine dose in the patients receiving hydrocortisone vs placebo

  72 hours

• Change in hourly diuresis in the patients receiving hydrocortisone vs placebo

  72 hours

• Change in the echocardiography parameters (fractional shortening and cardiac output) in the patients receiving hydrocortisone vs placebo

  72 hours

Study Arms (2)

Hydrocortisone

ACTIVE COMPARATOR

Hydrocortisone is the pharmaceutical term for cortisol, the principal glucocorticoid secreted by the adrenal gland

Drug: Hydrocortisone

Placebo

PLACEBO COMPARATOR

Isotonic sodium chloride is an aqueous solution of 0.9 percent sodium chloride which is isotonic with the blood and tissue fluid

Drug: Placebo

Interventions

Hydrocortisone DRUG

4 \* 0,5 mg/kg /24 hours (in every 6 hours) iv., during hypothermia treatment (max. 72 hours)

Also known as: Solu-Cortef

Hydrocortisone

Placebo DRUG

4 \* 2 ml isotonic sodium chloride solution /24 hours (in every 6 hours) iv., during hypothermia treatment (max. 72 hours)

Also known as: Isotonic saline

Placebo

Eligibility Criteria

• Age: Up to 72 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• Signed informed consent is unavailable.
• Infants who are expected to be \> 6 hours of age (not suitable for cooling).
• Congenital abnormalities, cardiac anomalies, meconium aspiration syndrome.
• Low blood pressure coincides with high heart rate (\>120/min) in cooled infants, suggesting hypovolaemia.
• Haematocrit level \< 35%.
• Need for combined, ≥2 types of inotropic therapy.

Sponsors & Collaborators

• Semmelweis University: lead

Study Sites (1)

Semmelweis University, 1st Department of Paediatrics

Budapest, Pest County, 1083, Hungary

Location

Related Publications (10)

• 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.

  PMID: 19797281 BACKGROUND

• Noori S, Friedlich P, Wong P, Ebrahimi M, Siassi B, Seri I. Hemodynamic changes after low-dosage hydrocortisone administration in vasopressor-treated preterm and term neonates. Pediatrics. 2006 Oct;118(4):1456-66. doi: 10.1542/peds.2006-0661.

  PMID: 17015536 BACKGROUND

• Ibrahim H, Sinha IP, Subhedar NV. Corticosteroids for treating hypotension in preterm infants. Cochrane Database Syst Rev. 2011 Dec 7;2011(12):CD003662. doi: 10.1002/14651858.CD003662.pub4.

  PMID: 22161379 BACKGROUND

• Rios DR, Moffett BS, Kaiser JR. Trends in pharmacotherapy for neonatal hypotension. J Pediatr. 2014 Oct;165(4):697-701.e1. doi: 10.1016/j.jpeds.2014.06.009. Epub 2014 Jul 16.

  PMID: 25039051 BACKGROUND

• Hebbar KB, Stockwell JA, Leong T, Fortenberry JD. Incidence of adrenal insufficiency and impact of corticosteroid supplementation in critically ill children with systemic inflammatory syndrome and vasopressor-dependent shock. Crit Care Med. 2011 May;39(5):1145-50. doi: 10.1097/CCM.0b013e31820eb4e4.

  PMID: 21336126 BACKGROUND

• Ng PC, Lam CW, Fok TF, Lee CH, Ma KC, Chan IH, Wong E. Refractory hypotension in preterm infants with adrenocortical insufficiency. Arch Dis Child Fetal Neonatal Ed. 2001 Mar;84(2):F122-4. doi: 10.1136/fn.84.2.f122.

  PMID: 11207229 BACKGROUND

• Ng PC, Lee CH, Bnur FL, Chan IH, Lee AW, Wong E, Chan HB, Lam CW, Lee BS, Fok TF. A double-blind, randomized, controlled study of a "stress dose" of hydrocortisone for rescue treatment of refractory hypotension in preterm infants. Pediatrics. 2006 Feb;117(2):367-75. doi: 10.1542/peds.2005-0869.

  PMID: 16452355 BACKGROUND

• Seri I, Tan R, Evans J. Cardiovascular effects of hydrocortisone in preterm infants with pressor-resistant hypotension. Pediatrics. 2001 May;107(5):1070-4. doi: 10.1542/peds.107.5.1070.

  PMID: 11331688 BACKGROUND

• 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.

  PMID: 31155392 RESULT

• Kovacs K, Szakmar E, Dobi M, Varga Z, Meder U, Szabo AJ, McNamara PJ, Szabo M, Jermendy A. Neurodevelopmental outcome in infants with neonatal encephalopathy receiving hydrocortisone during therapeutic hypothermia: follow-up of the extended-CORTISoL trial. J Perinatol. 2025 Dec;45(12):1788-1794. doi: 10.1038/s41372-025-02428-5. Epub 2025 Sep 22.

  PMID: 40983658 DERIVED

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain; Asphyxia; Shock

Interventions

Hydrocortisone; hydrocortisone hemisuccinate; Sodium Chloride

Condition Hierarchy (Ancestors)

Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Death; Pathologic Processes; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Miklós Szabó, MD, PhD

  Semmelweis University, 1st Department of Paediatrics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: assistant lecturer

Study Record Dates

• First Submitted: February 24, 2016
• First Posted: March 7, 2016
• Study Start: February 1, 2016
• Primary Completion: November 1, 2017
• Study Completion: December 15, 2022
• Last Updated: April 21, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1)