Septic Shock em Steroids

Mechanical Ventilation Clinical Trial

Official title:

Reposição de Esteróides em Crianças Com Choque Séptico

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01047670
• Other study ID #: Esteroides725
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: January 12, 2010
• Last updated: January 12, 2010
• Start date: May 2008

Study information

• Verified date: March 2008
• Source: Unidade de Terapia Intensiva
• Contact: Pedro Celiny Garcia, phd
• Phone: +55.51.3315.24.00
• Email: celiny[@]terra.com.br
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Month to 20 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Mechanical Ventilation
• Mortality

Intervention

Drug:
• Hydrocortisone
Hydrocortisone 6 mg/kg/day, 8 hourly, during 7 days or during the vasoactive drug infusion

Locations

Country	Name	City	State
Brazil	Hospital São Lucas da PUCRS	Porto Alegre	Rio Grande do Sul

Sponsors (1)

Lead Sponsor	Collaborator
Unidade de Terapia Intensiva

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	number of days free of vasoactive support after 7 days of septic shock diagnosis			No