None listed
Conditions
Brief summary
This multicentre pilot pragmatic open label randomized controlled Trial (RCT) compares early metabolic resuscitation treatment with Hydrocortisone, Vitamin C, and Thiamine in comparison to standard care defined as no treatment with Hydrocortisone, Vitamin C, and Thiamine. We hypothesize that in children presenting with sepsis and septic shock early intravenous administration of Vitamin C (30mg/kg iv q6h), Thiamine (4mg/kg q12h) and Hydrocortisone (1mg/kg q6h) delivered early during resuscitation is feasible. We hypothesize that these interventions will lead to a more rapid resolution of shock, reduced duration of organ dysfunction, leading to reduced intensive care resource utilisation. The study can provide the urgently needed evidence on currently used sepsis resuscitation bundles.
Interventions
Early Metabolic Resuscitation: After initial shock treatment including fluids and a first intravenous inotrope patients receive concomitant treatment with Hydrocortisone, Vitamin C, and Thiamine:
1. Ascorbic acid (Vitamin C). The dosing schedule is 30mg/kg intravenously every 6 hours for the duration of study treatment and will be infused over 1 hour.
2. Thiamine (Vitamin B1): The dosing schedule is 4mg/kg intravenously every 12 hours for the duration of study treatment and will be infused over
Early Metabolic Resuscitation: After initial shock treatment including fluids and a first intravenous inotrope patients receive concomitant treatment with Hydrocortisone, Vitamin C, and Thiamine: 1. Ascorbic acid (Vitamin C). The dosing schedule is 30mg/kg intravenously every 6 hours for the duration of study treatment and will be infused over 1 hour. 2. Thiamine (Vitamin B1): The dosing schedule is 4mg/kg intravenously every 12 hours for the duration of study treatment and will be infused over 1 hour. 3. Hydrocortisone: The dosing schedule is 1mg/kg intravenously every 6 hours for the duration of study treatment given as a slow bolus. Study drugs will be given through an existing intravenous line using. Drug delivery will occur through guardrails or similar system to ensure safe delivery of applied standardized drug concentrations. Study treatments will be given for a duration of 7 days, or until resolution of shock, discharge from intensive care unit, death, or occurrence of major side effects, whichever occurs first. Compliance with protocol will be assessed through the prospective institutional drug charts, and the prospective study case report form.
Sponsors
University of Queensland
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
28 Days to 17 Years
Healthy volunteers
No
Inclusion criteria
Children age =>28 days and <18 years which are admitted to the Paediatric Intensive Care Unit with a diagnosis of suspected septic shock requiring vasopressors/inotropes for >2hours (i.e. fluid-refractory shock).
Exclusion criteria
- Preterm babies born <34 weeks gestation that have a corrected age of <28 days - Known chronic renal failure not related to sepsis - Known chronic hepatic failure not related to sepsis - Known diseases affecting the steroid axis, including pituitary disease, congenital adrenal hypoplasia, Cushing or Addison’s disease - Palliative care patient/patient with limitation of treatment (not for inotropes, CPR, ECLS, intubation and ventilation) - Cardiopulmonary arrest in the past two hours requiring CPR >2 min, or death is deemed to be imminent or inevitable - Major bleeding with haemorrhagic shock - Sepsis is not likely to be the cause of shock - Known glucose-6 phosphate dehydrogenase (G-6PD) deficiency - Patients with sepsis/septic shock transferred form another ICU or hospital who have been treated with inotropes for septic shock for >24 hours - Patients with known history of oxalate nephropathy - Patients with acute beri-beri disease - Patients with acute Wernike’s encephalopathy - Patients with known malaria - Patients with known of suspected scurvy - Patient is receiving treatment for systemic fungal infection or has documented strongyloides infection at the time of randomization - Patient undergoing active chemotherapy for cancer treatment (incl. all administration routes) - Enrolment in RESPOND study <6 months ago (except for RESPOND ED randomization prior to RESPOND PICU within the same sepsis episode)
Outcome results
None listed