Overview
PALETTE is a perpetual adaptive platform to efficiently study sepsis interventions within 'treatable traits' in all-ages patients enabling prompt evaluation of pandemic treatments. Treatable traits, therapeutic targets identified by phenotypes or endotypes (defined by biological mechanism or by treatment response) through validated biomarkers (measurable characteristic reflecting normal or pathogenic processes, or treatment responses), may include multi-omics, cellular, immune, metabolic, endocrine features, or intelligent algorithms. PALETTE Bayesian adaptive design enables parallel investigations of multiple interventions for sepsis, and quick inclusion of pandemic pathogens. PALETTE's new conceptual model will respond to the challenges of standard approaches, i.e. series of sepsis trials, each investigating one or two interventions, expensive, time consuming, and inappropriate in pandemic context.
Eligibility
Platform inclusion criteria will be:
- All genders patients
- Aged \>37 weeks corrected gestational age
- Sepsis as per Sepsis-3 definition for adults, and as per the PHOENIX sepsis for children
Briefly, all following criteria will be required:
- Documented or suspected infection,
- Sequential Organ Failure Assessment (SOFA) score ≥2 for adults, and PHOENIX sepsis score of ≥2 for children.
- Health insurance
Platform exclusion criteria:
Any of the following:
- Refusal to consent for participating in the study,
- Pregnancy measured by beta-HCG blood levels
- Breast feeding
- Acute coronary disease in the past 3 months
- Stroke episode in the past 3 months
- Any condition for which patient's primary physician will consider inappropriate enrolling patient in the study
Treatable trait inclusion criteria :
- Hyperinflammation : Subphenotypes Beta, Delta, Gamma for adults; Subphenotypes PedSep-B, C, D for children
- Hypoinflammation : lymphocytes count \< 1.0 × 10\^9/L
- Macrophage Activation Like Syndrome : Ferritin \>4,420 ng/mL for adults, Ferritin \>500 ng/mL for children
- Corticosteroids: Positive for i-RECORDS algorithm signature
- Hypercoagulation (adults) : Prothrombin time (PT)/INR ≥ 1.40 AND Platelet count \< 150 000/mm3 or greater than 30% decrease in platelets in 24 hours
- Hypofibrinolysis (adults): Plasminogen deficit \< 0.5 µmol/L
There are also inclusion and exclusion criteria related to treatable traits and interventions.
