Asthma Acute, Exacerbation of Allergic Asthma
Conditions
Keywords
Asthma, Ketamine
Brief summary
This is a double-blinded, randomised, placebo-controlled trial enrolling 60 children aged 1 to 13 years with severe asthma exacerbation. All participants will receive standard therapy. Children not responding to standard therapy will be randomised to intervention arms. Randomization will occur in a 1:1 ratio using a computer-generated Excel sequence with permuted blocks of four, stratified by age (1-5 and 6-13 years). Patients will receive either nebulized ketamine (1 mg/kg every 6 hours for 24 hours) or 0.9% normal saline placebo. Randomization codes will be maintained by the hospital pharmacy, which will prepare identical numbered packs. During working hours, the pharmacist will dispense the allocated medication; at nights and weekends, pre-prepared packs will be stored securely in the PHDU/PICU under the supervision of the nursing in-charge. Blinding will be maintained for patients, clinicians, and outcome assessors. PRAM scores will be recorded at baseline and at 20, 60, 90, and 120 minutes post-dose. The primary outcome is pediatric respiratory assessment measure (PRAM) score change. Secondary outcomes include need for NIV or intubation and HDU/PICU length of stay.
Interventions
Group A (Ketamine) * Nebulised ketamine 1 mg/kg per dose every 6 hours for 24 hours (4 doses total). * Ketamine solution (e.g. 10 mg/mL) diluted with 0.9% saline to a total volume of 3-5 mL. Nebulisation will be delivered via jet nebuliser with oxygen flow 6-8 L/min using a mask. A dose will be considered complete when the nebuliser chamber is dry.
DRUGPlacebo
Nebulised 0.9% saline, 3-5 mL per dose, every 6 hours for 24 hours. Nebulisation will be delivered via jet nebuliser with oxygen flow 6-8 L/min using a mask. A dose will be considered complete when the nebuliser chamber is dry.
Sponsors
Sultan Qaboos University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Masking description
An independent statistician will generate a computer-based allocation list with variable permuted blocks, stratified by age group (1-5 vs 6-13 years). The hospital pharmacy will prepare 60 sequentially numbered, identical medication packs (001-060) containing either ketamine or 0.9% saline according to this concealed list. Packs will be visually indistinguishable (same volume and appearance); only the pack number will appear on the label. At enrolment, the bedside team will request the next available pack in sequence. Investigators, treating clinicians, parents/guardians, outcome assessors, and statisticians will remain blinded to treatment allocation.
Intervention model description
This is a phase-2 pilot designed to estimate effect size/variance, characterise safety, and assess feasibility. A total of 60 participants (30 per arm) will provide adequate precision around the mean difference in PRAM change and around AE rates to inform a future definitive phase-3 trial. Sample size of 60 (30 in each arm). The basis of sample size calculation is based on an assumption that mean change in PRAM at 60 minutes is -3.5 in ketamine arm vs -2 points in placebo hence between-group difference of 1.5 points favoring ketamine with assumed SD 2. Given that the expected number of patients with \>=3 points drop in PRAM in ketamine group is 33 and in placebo 17 with a study power 80% at level of error 5%. Minimum sample size required is 46 (23 in each arm)
Eligibility
Sex/Gender
ALL
Age
1 Years to 13 Years
Healthy volunteers
No
Inclusion criteria
* Children aged 1 to 13 years. * Diagnosis of severe asthma exacerbation (PRAM score 8-12) * Prior treatment with standard first-line management (beta-2 agonist, corticosteroid, magnesium sulfate)
Exclusion criteria
* Known allergy or adverse reaction to ketamine * Significant hemodynamic instability * Systemic hypertension \>95th percentile for age * Cardiac arrhythmias * Congestive heart failure * Obstructive sleep apnea with AHI \>5
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pediatric Respiratory Assessment Measure (PRAM) score. | Baseline and 20, 60, 90, and 120 minutes post-dose (over 24 hours) | Mean difference in the change in Pediatric Respiratory Assessment Measure (PRAM) score within 60 minutes of treatment between the nebulized ketamine and placebo groups. The PRAM is a validated clinical asthma severity score ranging from 0 to 12, where higher scores indicate more severe respiratory distress (a worse outcome) and a greater reduction indicates clinical improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants requiring non-invasive ventilation (NIV) or mechanical ventilation | Up to 24 hours after first dose | Number and percentage of participants who require escalation to non-invasive ventilation (NIV) or invasive mechanical ventilation during the treatment period. |
| Length of stay in the HDU/PICU | Through study completion, an average of 5 days | Duration of stay in the High Dependency Unit (HDU) or Pediatric Intensive Care Unit (PICU), measured in days. |
| Change in heart rate | Baseline and at 20, 60, 90, and 120 minutes post-dose, up to 24 hours | Change in heart rate (beats per minute) from baseline, monitored to assess therapeutic response and possible hemodynamic effects of the study medication. Unit: beats per minute |
| Change in respiratory rate | Baseline and at 20, 60, 90, and 120 minutes post-dose, up to 24 hours | Change in respiratory rate (breaths per minute) from baseline as a marker of clinical improvement. Unit: breaths per minute |
| Change in oxygen saturation | Baseline and at 20, 60, 90, and 120 minutes post-dose, up to 24 hours | Change in peripheral oxygen saturation (SpO2, %) from baseline as a marker of clinical improvement. Unit: percentage (%) |
Countries
Oman
Contacts
CONTACTZahra Ali Al Lawati
PRINCIPAL_INVESTIGATORZahraa Ali Al Lawati
College of Medicine and Health Sciences , Sultan Qaboos University
Outcome results
None listed