Paediatric Inflammatory Multisystem Syndrome-Temporally Associated With SARS-CoV-2 (PIMS-TS)
Conditions
Keywords
coronavirus-disease (COVID-19), SARS coronavirus 2 (SARS-CoV-2), tocilizumab, anakinra, Human normal immunoglobulin (IVIg), Methylprednisolone sodium succinate
Brief summary
The study is to provide reliable estimates of the effect of study treatment on hospital length of stay through to 28 days after randomisation. The protocol describes an overarching trial design to provide reliable evidence on the efficacy of candidate therapies for children hospitalised with PIMS-TS. It is an adaptive pragmatic platform trial with an open-label randomisation. New trial arms can be added as evidence emerges that other candidate therapeutics should be evaluated.
Detailed description
In May 2020 a new COVID-associated inflammatory syndrome in children was identified, Paediatric Inflammatory Multisystem Syndrome - Temporally associated with SARS-CoV-2 (PIMS-TS). A rapid international consensus process identified the need to evaluate corticosteroids and intravenous immunoglobulin (IVIg) as initial therapies in PIMS-TS, and confirmed tocilizumab and anakinra as biological anti-inflammatory agents to be evaluated as a second line therapy. This Swissped-Recovery trial is a sister trial to the RECOVERY international trial with the implementation of the study at Swiss study sites. The protocol describes an overarching trial design to provide reliable evidence on the efficacy of candidate therapies for children hospitalised with PIMS-TS. It is an adaptive pragmatic platform trial with an open-label randomisation. New trial arms can be added as evidence emerges that other candidate therapeutics should be evaluated. Additional substudies can be added to provide more detailed information on side effects or sub-categorisation of patient types.
Interventions
DRUGMethylprednisolone sodium succinate 10 mg/kg intravenously
Methylprednisolone sodium succinate 10 mg/kg intravenously once daily for 3 days (max 1 g per dose)
BIOLOGICALHuman normal immunoglobulin (IVIg)
Human normal immunoglobulin (IVIg) 2g/kg intravenously as a single dose in line with guidance for dosing and administration in Kawasaki disease
Sponsors
SwissPedNet
University Children's Hospital Basel
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Overarching trial design with treatment arms that are both available at the hospital and not believed by the enrolling doctor to be contraindicated (e.g. by particular co-morbid conditions or concomitant medications). Treatment arms to be added or removed according to the emerging evidence. Main randomisation part A: Methylprednisolone 2 mg/kg for three days intravenous or orally vs corticosteroids methylprednisolone 10mg/kg intravenous for three days vs intravenous immunoglobulin.
Eligibility
Sex/Gender
ALL
Age
44 Weeks to 18 Years
Healthy volunteers
No
Inclusion criteria
* Hospitalised children (aged \<18 years old) * SARS-CoV-2 infection associated disease (clinically suspected or laboratory confirmed) with evidence of single or multi-organ dysfunction (called Pediatric Multisystem Inflammatory Syndrome temporally associated with COVID-19 \[PIMS-TS\]). * No medical history that might, in the opinion of the attending clinician, put the patient at significant risk if he/she were to participate in the trial
Exclusion criteria
* Neonates/infants with a corrected gestational age of \<= 44 weeks * If the attending clinician believes that there is a specific contra-indication to one of the active drug treatment arms or that the patient should definitely be receiving one of the active drug treatment arms, then that arm will not be available for randomisation for that patient.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hospital length of stay | Within 28 days after randomisation | effect of study treatment on hospital length of stay |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-cause mortality among patients | Within 28 days and up to 6 months after randomisation | For each pairwise comparison with the 'no additional treatment' arm, the primary objective is to provide reliable estimates of the effect of study treatments on all-cause mortality. |
| Composite endpoint of death or need for mechanical ventilation or extracorporeal membrane oxygenation (ECMO) | Within 28 days and up to 6 months after randomisation | Among patients not on invasive mechanical ventilation at baseline, the number of patients with a composite endpoint of death or need for invasive mechanical ventilation or ECMO. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cardiac outcome (long-term impact) of PIMS-TS after discharge | Post-discharge extended follow-up visits up to 6 months after randomisation | Cardiac function and presence of coronary artery aneurysms will be assessed by echocardiography. |
| Neurological outcome (long-term impact) of PIMS-TS after discharge | Post-discharge extended follow-up visits up to 6 months after randomisation | assessment of post-traumatic stress disorder |
| Need for (and duration of) ventilation | Within 28 days and up to 6 months after randomisation | To assess the effects of study treatment on number of patients who needed any ventilation and (for invasive mechanical ventilation) the number of days it was required |
| Quality of life post-infection assessed by Strengths and Difficulties Questionnaire (SDQ) | Post-discharge extended follow-up visits up to 6 months after randomisation | The strengths and difficulties questionnaire (SDQ) is a short behavioural screening questionnaire for children aged 3 to 16. The 25 personality attributes in the SDQ are made up of 5 scales of 5 items each. The scales are: Emotional symptoms, Conduct problems, Hyperactivity/inattention, Peer relationship problems, Prosocial behaviour. Each subscale includes five items, rating each item as either: Never = 0, Somewhat True = 1 or Certainly True = 2. SDQ total scores of 17 and above are considered to be abnormal. |
| Health care costs | Within 28 days after randomisation | Direct hospitalization-related costs will be captured for health economic analyses. For each PIMS-TS related hospitalization episode recruited in the study, the total Diagnosis-Related Group (DRG) costs claimed by the respective study site will be extracted from the institutional finance records, and analysed in batch upon completion of recruitment |
| Need for renal replacement therapy | Within 28 days and up to 6 months after randomisation | To assess the effects of study treatment on number of patients who needed renal replacement therapy |
| Number of patients who had thrombotic events | Within 28 days and up to 6 months after randomisation | To assess the effects of study treatment on number of patients who had thrombotic events |
Countries
Switzerland
Outcome results
None listed