None listed
Conditions
Brief summary
Globally, a child dies from sepsis every 30 seconds. In Australia, one child dies every week, and many surviving children experience long term disability. We hypothesise that treatment of septic children with vitamin C and hydrocortisone will result in earlier shock resolution. We will perform a worldwide randomised controlled trial in paediatric sepsis which will test the use of Vitamin C (100 mg/kg 6 h) and Hydrocortisone (1 mg/kg 6 h) which has shown some promise in improving patient-centred outcomes in adults. The study will assess functional outcomes and quality of life, consumer engagement, and sepsis related costs. The wide dissemination of findings will increase awareness of sepsis and could save lives. In addition, we aim to establish a biobank of patient samples enrolled in the trial for sepsis biomarker studies.
Interventions
Patients will be allocated in a 1:1:1 ratio to the RESPOND treatment groups.
Arm 1 - Intervention 1 - Early intravenous resuscitation with Vitamin C and Hydrocortisone.
After initial shock treatment including fluids and a first intravenous inotrope, patients then receive concomitant treatment with Vitamin C and Hydrocortisone.
Ascorbic acid (Vitamin C): the dosing schedule is 100 mg/kg (maximum 5,000 mg per dose) intravenously every 6 hours for the duration of study treatment and will be infused
Patients will be allocated in a 1:1:1 ratio to the RESPOND treatment groups. Arm 1 - Intervention 1 - Early intravenous resuscitation with Vitamin C and Hydrocortisone. After initial shock treatment including fluids and a first intravenous inotrope, patients then receive concomitant treatment with Vitamin C and Hydrocortisone. Ascorbic acid (Vitamin C): the dosing schedule is 100 mg/kg (maximum 5,000 mg per dose) intravenously every 6 hours for the duration of study treatment and will be infused over 60 minutes. Hydrocortisone: The dosing schedule is 1 mg/kg (maximum 50 mg per dose) intravenously infused over 5 minutes every 6 hours for the duration of study treatment given as a slow bolus. Arm 2 - Intervention 2 - Hydrocortisone only. Hydrocortisone: the dosing schedule is 1mg/kg (maximum 50 mg per dose) intravenously infused over 5 minutes every 6 hours for the duration of study treatment given as a slow bolus. All three arms will be monitored for adherence to interventions by a formal data monitoring and audit of the medication records. Duration of treatment After shock resolution - defined as cessation of inotropes for at least 4 hours - or after a maximum of 72hours study drugs should be ceased. The treatment will continue until (whichever occurs first): - Septic shock resolves defined as ability to cease inotropes for less than 4 hours with good perfusion and no signs of shock. - 72 hours of treatment has been administered - The patient is discharged from ICU - Contraindications to Vitamin C or Hydrocortisone therapy arise - Death occurs - Serious adverse events suspected to be secondary to the intervention therapy develop
Sponsors
The 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
7 Days to 17 Years
Healthy volunteers
No
Inclusion criteria
Criterion 1: Child aged >=7 days and <18 years and admitted to PICU. Criterion 2: Treatment of septic shock with vasopressor/inotrope therapy for >1 hour
Exclusion criteria
- Corrected age of <7 days - 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 - Receiving ongoing treatment with inotropes/vasopressors for confirmed or suspected sepsis/septic shock for >24 hours - Patients with known glucose-6 phosphate dehydrogenase (G-6PD) deficiency - Patients with known history of oxalate nephropathy - Patients with known malaria - Patients receiving cyanocobalamin or deferoxamine - Enrolment in RESPOND study within the past 6 months
Outcome results
None listed