Septic Shock em Steroids

Reposição de Esteróides em Crianças Com Choque Séptico

Septic shock is a frequent reason for admission on pediatric intensive care units. Interventions which can change morbidity and mortality of septic shock patients are of great interest. Steroid replacement in adults with severe sepsis and septic shock have been extensively studied. It was recently demonstrated that low dose steroid (< 300mg/ day) used for more than 5 days was associated with decreased mortality and lower requirement of vasoactive support in the adult population that had a low response to the ACTH test. However, this was not confirmed in the latest results from the CORTICUS study. Use of low dose hydrocortisone, or any other steroid has not been studied in critically ill children. Mortality associated with sepsis in children has decreased in the last decade and currently it is close to 10%, making it difficult to power a study able to show reduced mortality. Taking into account the results from previous studies reporting the high incidence of adrenal failure and its association to worse outcome, we have designed a clinical trial to evaluate the effect of low dose hydrocortisone in children with septic shock: Cortisol Replacement in Children with Sepsis Study.

Study Overview

• Status: Unknown
• Conditions: Mortality; Mechanical Ventilation
• Intervention / Treatment: Drug: Hydrocortisone

Detailed Description

Hypothesis Pediatric patients with septic shock have a high incidence of failure to respond to the ACTH test and would benefit of steroid replacement.

Design Randomized double-blind placebo controlled clinical trail. Outcome Primary: number of days free of vasoactive support after 7 days of septic shock diagnosis.

Methods

Study population:

All children admitted to PICU will be possible enrolled. Inclusion criteria will be (I) age between 1 month and 16 years; (II) septic shock according to the definitions of pediatric septic shock 2005; (III) inotrope requirement, as in dopamine > 5 mcg/kg/mim, dobutamine > 5 mcg/kg/min or any dose of noradrenaline or adrenaline after adequate fluid resuscitation. Exclusion criteria will be patients with (I) baseline disease associated to HPA axis dysfunction; (II) steroid use in the past 4 weeks; (III) previous use of etomidate; (IV) formal indication for steroids use, and (V) formal contraindication to steroid use.

Stratification criteria:

Patients will be stratified by age, gender, PRISM category, failure to respond to ACTH test, surgical patients, chronic patient, baseline cardiac and oncological disease and presence of ARDS.

Intervention:

Hydrocortisone 6 mg/kg/day, 8 hourly, during 7 days or during the vasoactive drug infusion. The control group will receive placebo.

Randomization:

Randomization will be carried through numbered envelopes, randomized prior to the study beginning, in blocks of 10, ratio 1:1.

Protocol:

Identical vials with hydrocortisone or placebo will be prepared in an industrial pharmacy and labeled using alphabetic letters (A, B, C, D) before the beginning of the study. Each vial of hydrocortisone will have 100 mg of hydrocortisone ponder to be diluted in 10 ml of normal saline 0.9% Each vial of placebo will content a innocuous ponder, also to be diluted in 10 ml of normal saline 0.9%. The drug and its referent letter (A, B, C, D) will be controlled by two lists, handed in by the pharmacist to the researchers inside closed envelopes before the beginning of the study. After enrollment and randomization, children joining the study will have baseline cortisol and ACTH measured. ACTH testes (1 mcg/ 1.75m2 and 250 mcg) will be performed, 4 hours apart. After this, patients will receive the study drug (either hydrocortisone or placebo), 0.2 ml/kg/ dose, 8 hourly. This will last the period the patient requires vasoactive support, or a maximum of 7 days. Daily routine blood results will be noted, as well as a further ACTH test on day 3 if the patient is still on vasoactive support. Demographic data will be collected on enrollment.

• Study Type: Interventional
• Enrollment (Anticipated): 160
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
      • Recruiting
      • Hospital Sao Lucas da PUCRS
      • Contact: Pedro Celiny Garcia, phd; Phone Number: +55.51.3315.24.00; Email: celiny@terra.com.br
      • Contact: Carolina Friedrich Amoretti, md; Phone Number: +55 51 3339 6474; Email: cfamoretti@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 20 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• (I) age between 1 month and 20 years;
• (II) septic shock according to the definitions of paediatric septic shock 2005; -(III) inotrope requirement, as in dopamine > 5 mcg/kg/mim, dobutamine > 5 mcg/kg/min or any dose of noradrenaline or adrenaline after adequate fluid resuscitation. -

Exclusion Criteria:

Exclusion criteria will be patients with

• (I) baseline disease associated to HPA axis dysfunction;
• (II) steroid use in the past 4 weeks;
• (III) previous use of etomidate; (IV) formal indication for steroids use, and
• (V) formal contraindication to steroid use.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2; placebo	Drug: Hydrocortisone; Hydrocortisone 6 mg/kg/day, 8 hourly, during 7 days or during the vasoactive drug infusion
Experimental: 1; Hydrocortisone 6 mg/kg/day, 8 hourly, during 7 days or during the vasoactive drug infusion	Drug: Hydrocortisone; Hydrocortisone 6 mg/kg/day, 8 hourly, during 7 days or during the vasoactive drug infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
number of days free of vasoactive support after 7 days of septic shock diagnosis

Collaborators and Investigators

• Sponsor: Unidade de Terapia Intensiva

Study record dates

Study Major Dates

• Study Start: May 1, 2008

Study Registration Dates

• First Submitted: January 12, 2010
• First Submitted That Met QC Criteria: January 12, 2010
• First Posted (Estimate): January 13, 2010

Study Record Updates

• Last Update Posted (Estimate): January 13, 2010
• Last Update Submitted That Met QC Criteria: January 12, 2010
• Last Verified: March 1, 2008

More Information

Terms related to this study

• Keywords: sepsis, shock, adrenal insufficiency, hydrocortisone, children, paediatric intensive care.; number of days free of vasoactive support in 7 days; days free of mechanical ventilation; PICU mortality; mortality among patient with inappropriate response to the ACTH test; baseline cortisol/ PIM2 correlation
• Additional Relevant MeSH Terms: Anti-Inflammatory Agents; Hydrocortisone
• Other Study ID Numbers: Esteroides725