Early Hydrocortisone Versus Regular Treatment in Shock in Extremely Preterm Neonates - an Open Randomized Controlled Trial

NCT07248761 | Active Not Recruiting Phase 4 DMC

• 1 other identifier: R-2024-3606-155
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to determine the effectiveness of early use of hydrocortisone (since the diagnosis of shock) for its resolution within the first 72 hours in premature infants under 1,500 g. The main questions it aims to answer are:

• Does the early use of hydrocortisone help solve shock in preterm infants under 1500 g faster than the standard treatment?
• Does the early use of hydrocortisone help prevent death within the first seven days of presentation of shock in comparison to premature infants who receive regular treatment? Researchers will compare the early use of hydrocortisone plus the standard treatment to solve shock against just standard treatment. Participants will:
• Be randomized to receive standard treatment for shock according to their neonatologist or this standard treatment plus hydrocortisone as soon as the diagnosis is done and treatment is started.
• Be followed either until shock is solved or if they present death due to this event of shock.

Conditions

Shock; Preterm Birth Complication; Preterm Intraventricular Hemorrhage; Asphyxia Perinatal; Distress Respiratory Syndrome; Hyperglycaemia (Non Diabetic); Neonatal Sepsis, Early-Onset; Neonatal Sepsis, Late-Onset; NEC - Necrotizing Enterocolitis; Patent Ductus Arteriosus in Preterm Infants; Intestinal Perforation

Keywords

Preterm neonates; Shock; Treatment; Hydrocortisone; Early

Outcome Measures

Primary Outcomes (1)

• Shock resolution

  The patient is hemodynamically stable and no longer requires vasoactive support.

  72 hours

Secondary Outcomes (1)

• Mortality.

  Seven days.

Study Arms (2)

Preterm neonates in shock who receive regular treatment.

ACTIVE COMPARATOR

The treatment this group receives is determined by the attending neonatologist. It may o may not include Hydrocortisone at some point of the evolution of the disease.

Other: Vasoactive drug therapies

Preterm neonates in shock who receive regular treatment plus Hydrocortisone from the beginning.

EXPERIMENTAL

This group receives the treatment that the attending neonatologist determines plus Hydrocortisone since the initiation of vasoactive drugs.

Drug: Intravascular Hydrocortisone (stress dosage): 1 mg/k/dose each 8 hours for 5 days

Interventions

Intravascular Hydrocortisone (stress dosage): 1 mg/k/dose each 8 hours for 5 days DRUG

The "Early Hydrocortisone Group" will be receiving Hydrocortisone since the diagnosis of shock and the vasoactive drugs are initiated.

Preterm neonates in shock who receive regular treatment plus Hydrocortisone from the beginning.

Vasoactive drug therapies OTHER

This group will receive the treatment that the attending physician will decide. It may include any kind of vasoactive drug and, at some point, Hydrocortisone if the attending considers the patient is going through a "Vasoactive resistant shock".

Preterm neonates in shock who receive regular treatment.

Eligibility Criteria

• Age: 0 Days - 14 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Preterm babies of 1,500 g or less
• Diagnosis of shock by attending physician during their first 14 days of life

You may not qualify if:

• Major physical malformations that compromise life itself.
• Preterm newborns with probable Congenital Adrenal Hyperplasia

Sponsors & Collaborators

• Coordinación de Investigación en Salud, Mexico: lead
• Instituto Mexicano del Seguro Social: collaborator

Study Sites (1)

UMAE Hospital de Gineco Obstetricia No. 4 "Luis Castelazo Ayala", IMSS

Mexico City, ALVARO OBREGON, 01090, Mexico

Location

Related Publications (40)

• Patra K, Greene MM, Silvestri JM. Neurodevelopmental impact of hydrocortisone exposure in extremely low birth weight infants: outcomes at 1 and 2 years. J Perinatol. 2015 Jan;35(1):77-81. doi: 10.1038/jp.2014.133. Epub 2014 Jul 31.

  PMID: 25078865 BACKGROUND

• Rademaker KJ, Uiterwaal CS, Groenendaal F, Venema MM, van Bel F, Beek FJ, van Haastert IC, Grobbee DE, de Vries LS. Neonatal hydrocortisone treatment: neurodevelopmental outcome and MRI at school age in preterm-born children. J Pediatr. 2007 Apr;150(4):351-7. doi: 10.1016/j.jpeds.2006.10.051.

  PMID: 17382109 BACKGROUND

• Baud O, Maury L, Lebail F, Ramful D, El Moussawi F, Nicaise C, Zupan-Simunek V, Coursol A, Beuchee A, Bolot P, Andrini P, Mohamed D, Alberti C; PREMILOC trial study group. Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial. Lancet. 2016 Apr 30;387(10030):1827-36. doi: 10.1016/S0140-6736(16)00202-6. Epub 2016 Feb 23.

  PMID: 26916176 BACKGROUND

• Ramaswamy VV, Kumar G, Pullattayil S AK, Aradhya AS, Suryawanshi P, Sahni M, Khurana S, Saini SS, K R, Dhir SK, Chawla D, Kumar P, More K. Timing of hydrocortisone therapy in neonates with shock: a systematic review, meta-analysis, and clinical practice guideline. Front Pediatr. 2025 Mar 12;13:1491976. doi: 10.3389/fped.2025.1491976. eCollection 2025.

  PMID: 40144277 BACKGROUND

• Kumbhat N, Noori S. Corticosteroids for Neonatal Hypotension. Clin Perinatol. 2020 Sep;47(3):549-562. doi: 10.1016/j.clp.2020.05.015. Epub 2020 May 22.

  PMID: 32713450 BACKGROUND

• Agakidou E, Chatziioannidis I, Kontou A, Stathopoulou T, Chotas W, Sarafidis K. An Update on Pharmacologic Management of Neonatal Hypotension: When, Why, and Which Medication. Children (Basel). 2024 Apr 19;11(4):490. doi: 10.3390/children11040490.

  PMID: 38671707 BACKGROUND

• Dudeja S, Saini SS, Sundaram V, Dutta S, Sachdeva N, Kumar P. Early hydrocortisone verses placebo in neonatal shock- a double blind Randomized controlled trial. J Perinatol. 2025 Mar;45(3):342-349. doi: 10.1038/s41372-025-02222-3. Epub 2025 Feb 13.

  PMID: 39948354 BACKGROUND

• Watterberg KL, Shaffer ML, Mishefske MJ, Leach CL, Mammel MC, Couser RJ, Abbasi S, Cole CH, Aucott SW, Thilo EH, Rozycki HJ, Lacy CB. Growth and neurodevelopmental outcomes after early low-dose hydrocortisone treatment in extremely low birth weight infants. Pediatrics. 2007 Jul;120(1):40-8. doi: 10.1542/peds.2006-3158.

  PMID: 17606560 BACKGROUND

• 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.

  PMID: 27156187 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

• Altit G, Vigny-Pau M, Barrington K, Dorval VG, Lapointe A. Corticosteroid Therapy in Neonatal Septic Shock-Do We Prevent Death? Am J Perinatol. 2018 Jan;35(2):146-151. doi: 10.1055/s-0037-1606188. Epub 2017 Aug 24.

  PMID: 28838003 BACKGROUND

• Higgins S, Friedlich P, Seri I. Hydrocortisone for hypotension and vasopressor dependence in preterm neonates: a meta-analysis. J Perinatol. 2010 Jun;30(6):373-8. doi: 10.1038/jp.2009.126. Epub 2009 Aug 20.

  PMID: 19693023 BACKGROUND

• Subhedar NV, Duffy K, Ibrahim H. Corticosteroids for treating hypotension in preterm infants. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD003662. doi: 10.1002/14651858.CD003662.pub3.

  PMID: 17253493 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

• 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

• Efird MM, Heerens AT, Gordon PV, Bose CL, Young DA. A randomized-controlled trial of prophylactic hydrocortisone supplementation for the prevention of hypotension in extremely low birth weight infants. J Perinatol. 2005 Feb;25(2):119-24. doi: 10.1038/sj.jp.7211193.

  PMID: 15329742 BACKGROUND

• Salas G, Travaglianti M, Leone A, Couceiro C, Rodriguez S, Farina D. [Hydrocortisone for the treatment of refractory hypotension: a randomized controlled trial]. An Pediatr (Barc). 2014 Jun;80(6):387-93. doi: 10.1016/j.anpedi.2013.08.004. Epub 2013 Oct 16. Spanish.

  PMID: 24139558 BACKGROUND

• Morabito LA, Corica D, Pepe G, Li Pomi A, Aversa T, Wasniewska MG. Critical illness-related corticosteroid insufficiency (CIRCI) in paediatric patients: a diagnostic and therapeutic challenge. Ital J Pediatr. 2024 Mar 11;50(1):46. doi: 10.1186/s13052-024-01616-x.

  PMID: 38462639 BACKGROUND

• Rulli I, Carcione AM, D'Amico F, Quartarone G, Chimenz R, Gitto E. Corticosteroids in Pediatric Septic Shock: A Narrative Review. J Pers Med. 2024 Dec 17;14(12):1155. doi: 10.3390/jpm14121155.

  PMID: 39728068 BACKGROUND

• Schlapbach LJ, Watson RS, Sorce LR, Argent AC, Menon K, Hall MW, Akech S, Albers DJ, Alpern ER, Balamuth F, Bembea M, Biban P, Carrol ED, Chiotos K, Chisti MJ, DeWitt PE, Evans I, Flauzino de Oliveira C, Horvat CM, Inwald D, Ishimine P, Jaramillo-Bustamante JC, Levin M, Lodha R, Martin B, Nadel S, Nakagawa S, Peters MJ, Randolph AG, Ranjit S, Rebull MN, Russell S, Scott HF, de Souza DC, Tissieres P, Weiss SL, Wiens MO, Wynn JL, Kissoon N, Zimmerman JJ, Sanchez-Pinto LN, Bennett TD; Society of Critical Care Medicine Pediatric Sepsis Definition Task Force. International Consensus Criteria for Pediatric Sepsis and Septic Shock. JAMA. 2024 Feb 27;331(8):665-674. doi: 10.1001/jama.2024.0179.

  PMID: 38245889 BACKGROUND

• Schwarz CE, Dempsey EM. Management of Neonatal Hypotension and Shock. Semin Fetal Neonatal Med. 2020 Oct;25(5):101121. doi: 10.1016/j.siny.2020.101121. Epub 2020 May 21.

  PMID: 32473881 BACKGROUND

• Ng PC, Lam CW, Lee CH, Ma KC, Fok TF, Chan IH, Wong E. Reference ranges and factors affecting the human corticotropin-releasing hormone test in preterm, very low birth weight infants. J Clin Endocrinol Metab. 2002 Oct;87(10):4621-8. doi: 10.1210/jc.2001-011620.

  PMID: 12364445 BACKGROUND

• Ng PC, Lee CH, Lam CW, Ma KC, Fok TF, Chan IH, Wong E. Transient adrenocortical insufficiency of prematurity and systemic hypotension in very low birthweight infants. Arch Dis Child Fetal Neonatal Ed. 2004 Mar;89(2):F119-26. doi: 10.1136/adc.2002.021972.

  PMID: 14977894 BACKGROUND

• van de Loo M, van Kaam A, Offringa M, Doyle LW, Cooper C, Onland W. Corticosteroids for the prevention and treatment of bronchopulmonary dysplasia: an overview of systematic reviews. Cochrane Database Syst Rev. 2024 Apr 10;4(4):CD013271. doi: 10.1002/14651858.CD013271.pub2.

  PMID: 38597338 BACKGROUND

• Baud O, Torchin H, Butin M, Flamant C, Nuytten A. Prophylactic low-dose hydrocortisone in neonates born extremely preterm: current knowledge and future challenges. Pediatr Res. 2025 Jul;98(1):65-71. doi: 10.1038/s41390-024-03756-6. Epub 2024 Nov 26.

  PMID: 39592771 BACKGROUND

• Ng PC, Wong SP, Chan IH, Lam HS, Lee CH, Lam CW. A prospective longitudinal study to estimate the "adjusted cortisol percentile" in preterm infants. Pediatr Res. 2011 Jun;69(6):511-6. doi: 10.1203/PDR.0b013e31821764b1.

  PMID: 21364494 BACKGROUND

• Baud O, Watterberg KL. Prophylactic postnatal corticosteroids: Early hydrocortisone. Semin Fetal Neonatal Med. 2019 Jun;24(3):202-206. doi: 10.1016/j.siny.2019.04.007. Epub 2019 Apr 20.

  PMID: 31043325 BACKGROUND

• Huysman MW, Hokken-Koelega AC, De Ridder MA, Sauer PJ. Adrenal function in sick very preterm infants. Pediatr Res. 2000 Nov;48(5):629-33. doi: 10.1203/00006450-200011000-00013.

  PMID: 11044483 BACKGROUND

• Quintos JB, Boney CM. Transient adrenal insufficiency in the premature newborn. Curr Opin Endocrinol Diabetes Obes. 2010 Feb;17(1):8-12. doi: 10.1097/MED.0b013e32833363cc.

  PMID: 19881342 BACKGROUND

• Kharrat A, Diambomba Y, Jain A. Corticosteroid use in neonatal hypotension: A survey of Canadian neonatologists. Pediatr Neonatol. 2024 Sep;65(5):451-456. doi: 10.1016/j.pedneo.2023.09.013. Epub 2024 Feb 5.

  PMID: 38388227 BACKGROUND

• Ng PC. Adrenocortical insufficiency and refractory hypotension in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2016 Nov;101(6):F571-F576. doi: 10.1136/archdischild-2016-311289. Epub 2016 Sep 6.

  PMID: 27601464 BACKGROUND

• Spaggiari V, Passini E, Crestani S, Roversi MF, Bedetti L, Rossi K, Lucaccioni L, Baraldi C, Della Casa Muttini E, Lugli L, Iughetti L, Berardi A. Neonatal septic shock, a focus on first line interventions. Acta Biomed. 2022 Jul 1;93(3):e2022141. doi: 10.23750/abm.v93i3.12577.

  PMID: 35775767 BACKGROUND

• Saini SS, Shrivastav AK, Kumar J, Sundaram V, Mukhopadhyay K, Dutta S, Ray P, Kumar P. Predictors of Mortality in Neonatal Shock: A Retrospective Cohort Study. Shock. 2022 Feb 1;57(2):199-204. doi: 10.1097/SHK.0000000000001887.

  PMID: 34798634 BACKGROUND

• Seri I, Noori S. Diagnosis and treatment of neonatal hypotension outside the transitional period. Early Hum Dev. 2005 May;81(5):405-11. doi: 10.1016/j.earlhumdev.2005.03.008.

  PMID: 15882935 BACKGROUND

• Bhat BV, Plakkal N. Management of Shock in Neonates. Indian J Pediatr. 2015 Oct;82(10):923-9. doi: 10.1007/s12098-015-1758-7. Epub 2015 May 21.

  PMID: 25990594 BACKGROUND

• Mullaly R, El-Khuffash AF. Haemodynamic assessment and management of hypotension in the preterm. Arch Dis Child Fetal Neonatal Ed. 2024 Feb 19;109(2):120-127. doi: 10.1136/archdischild-2022-324935.

  PMID: 37173119 BACKGROUND

• Cayabyab R, McLean CW, Seri I. Definition of hypotension and assessment of hemodynamics in the preterm neonate. J Perinatol. 2009 May;29 Suppl 2:S58-62. doi: 10.1038/jp.2009.29.

  PMID: 19399011 BACKGROUND

• Wu TW, Noori S. Recognition and management of neonatal hemodynamic compromise. Pediatr Neonatol. 2021 Feb;62 Suppl 1:S22-S29. doi: 10.1016/j.pedneo.2020.12.007. Epub 2020 Dec 24.

  PMID: 33485823 BACKGROUND

• Johnson PJ. Hydrocortisone for Treatment of Hypotension in the Newborn. Neonatal Netw. 2015;34(1):46-51. doi: 10.1891/0730-0832.34.1.46.

  PMID: 26803045 BACKGROUND

• Barrington KJ. Hypotension and shock in the preterm infant. Semin Fetal Neonatal Med. 2008 Feb;13(1):16-23. doi: 10.1016/j.siny.2007.09.002. Epub 2007 Oct 31.

  PMID: 17974512 BACKGROUND

MeSH Terms

Conditions

Shock; Pulmonary Atelectasis; Hyperglycemia; Neonatal Sepsis; Enterocolitis, Necrotizing; Intestinal Perforation

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lung Diseases; Respiratory Tract Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Sepsis; Infections; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Systemic Inflammatory Response Syndrome; Inflammation; Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• ELISA DORANTES ACOSTA, PH D HEALTH SCIENCES

  Hospital Infantil de Mexico Federico Gomez

  STUDY DIRECTOR

• EDITH VALDEZ MARTINEZ, PH D MEDICAL ETHICS

  Unidad de Investigación Médica en Epidemiología Clínica, UMAE Hospital de Pediatría, CMN SXXI, IMSS

  STUDY DIRECTOR

• HORACIO MARQUEZ GONZALEZ, PH D HEALTH SCIENCES

  Unidad de investigación, Hospital Infantil de México Federico Gómez / Cardiopatías Congénitas, UMAE Hospital de Cardiología, CMN SXXI, IMSS.

  STUDY CHAIR

• ADRIANA APOLONIO, MARTINEZ

  Servicio de Cardiología Pediátrica y Perinatal de la UMAE HGO4, IMSS

  STUDY CHAIR

• MARIA DEL CARMEN JIMENEZ MARTINEZ, PH D IMMUNOLOGY

  POSGRADO EN CIENCIAS MÉDICAS DE LA FACULTAD DE MEDICINA DE LA UNAM

  STUDY CHAIR

• FLOR DE MARIA GRANADOS CANSECO, MASTER´S D HEALTH SCIENCES

  UMAE, HOSPITAL DE GINECO-OBSTETRICIA NO. 4 "LUIS CASTELAZO AYALA", IMSS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: The regular group will receive the treatment for shock according to their attending neonatologist. The experimental group will receive the same treatment plus Hydrocortisone parallel to the first vasoactive drug.

Study Record Dates

• First Submitted: November 18, 2025
• First Posted: November 25, 2025
• Study Start: February 1, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): July 30, 2026
• Last Updated: November 25, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Unending.
• Access Criteria: Pediatricians, Neonatologists, Cardiologists, Intensive Care Pediatricians Epidemiological variables / Clinical variables / Outcomes All statistical analyses will be available if asked for by e-mail. Every investigator already included will be able to review requests via electronic mail.

Locations

ME (1)