Adaptive Platform Trial for Personnalisation of Sepsis Treatment in Children and Adults: a Multi-national, Treatable Traits-guided, Adaptive, Bayesian Basket Trial
- Conditions
- Sepsis
- Interventions
- Drug: Low molecular weight heparinDrug: Recombinant humanThrombomodulin( rhTM)Biological: Fresh frozen plasmaOther: Usual care
- Registration Number
- NCT06381661
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 2000
- All genders patients aged >37 weeks corrected gestational age with sepsis as per Sepsis-3 definition for adults, and as per the PHOENIX sepsis for children
- documented or suspected infection
- a Sequential Organ Failure Assessment (SOFA) score ≥2 for adults, and PHOENIX sepsis score of ≥2 for children.
Domain specific additional inclusion criteria :
-
Hyper or hypo inflammation based
- For adults on, respectively: beta, delta and gamma sub-phenotypes, and/or circulating levels of IL-6 > 100pg/mL, and lymphocytes counts < 1.0 × 109/L and/or HLA-DR <5,000 HLA-DR receptors/monocytes
- For children on: the PODIUM (+specific criteria for children)
-
Corticosteroids domain Corticosteroids responses based on the combination of Glucocorticoid-induced 1 GLCCI1) AA and nuclear factor (NF)-KB1 DI genotypes.
-
Coagulation domain
- Hypercoagulation state defined as a SIC score ≥4 points and neutrophils side fluorescence light (NEUT-SFL) >66 Arbitrary Units (patients with disseminated intravascular coagulopathy, DIC) or NEUT-SFL ≤66 AU (septic coagulopathy)
- Hypofibrinolytic state defined as SIC score ≥4 points and decreased plasminogen level <1.2 nM.
- refused to consent participating in the study
- pregnancy
- any condition for which patient's primary physician will consider inappropriate enrolling patient in the study
- previous enrollment in the study.
- additional domain specific exclusion criteria relevant to specific interventions, i.e. tocilizumab, baricitinib, anakinra, hydrocortisone, fludrocortisone, unfractioned heparin, tinzaparin, human recombinant thrombomodulin, sivelestat, fresh frozen plasma, according to the "base de données publiques des medicaments"
Patients can be included in multiple domains.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Immuno-modulation : Tocilizumab Tocilizumab - Cortico-steroids :Hydrocortisone and fludrocotisone Hydrocortisone and fludrocortisone - Coagulation : Heparin Heparin - Coagulation : Low molecular weight heparin Low molecular weight heparin - Coagulation : Recombinant humanThrombomodulin( rhTM) Recombinant humanThrombomodulin( rhTM) - Coagulation : Sivelestat Sivelestat - Coagulation : Fresh Frozen Plasma Fresh frozen plasma - Control Usual care - Immuno-modulation Baricitinib Baricitinib - Immuno-modulation Anakinra Anakinra - Cortico-steroids : Hydrocortisone Hydrocortisone -
- Primary Outcome Measures
Name Time Method All-cause mortality At day 28 Number of patients with persistent life-supportive therapies At day 28 Respiratory support: non-invasive, invasive mechanical ventilation; cardiovascular support: continuous infusion of any dose of vasopressor or inotrope; renal support: intermittent or continuous renal replacement therapy
- Secondary Outcome Measures
Name Time Method Composite of the two primary outcomes At day 28 All deaths are scored "-1" on the ordinal scale, i.e., the worst outcome. Then to assess important changes in outcome for survivors, the number of days free of organ support up until day 28 is calculated, with higher score indicating faster recovery. Organ support is defined as needing either respiratory, cardiovascular or renal support. Respiratory support is defined as invasive mechanical ventilation or non-invasive ventilation including continuous positive airway pressure or high-flow nasal oxygen with an FiO2≥0.4 and a flow rate ≥30L/min. Cardiovascular support is defined as ongoing infusion of any dose of any vasopressor or inotrope drug. Renal support is defined by the requirement of renal replacement therapy regardless of treatment modalities.
Overall Survival At 3 years Number of hospital free days At 3 years Time to recover walking At day 90 Time to resume previous social and professional activities At 1 year Quality of life score for adults assessed by SF-36 At 3 years The Short Form (36) (SF-36) Health Survey is a 36-item measure if health status. The score obtained varies between 0 and 100. The higher the score the less disability.
Ware JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection. Med Care 1992;30:473-83.Quality of life score for adults assessed by EQ-5D-5L At 3 years EQ-5D-5L : It evaluates five dimensions : mobility, self-care, usual activities, pain/discomfort and anxiety/depression and each dimension has five levels : no problems, slight problems, moderate problems, severe problems and extreme problems. Answers are given on a 5-point scale by domain, the higher the score, the poorer the quality of life.
Quality of life score for children assessed by FFS At 3 years Functional Status Scale (FFS) : It examines 6 domains of functioning, and each domain receives a score of 1 (normal), 2 (mild dysfunction), 3 (moderate dysfunction), 4 (severe dysfunction), or 5 (very severe dysfunction). Final scores range from 6 to 30.
Number of adverse events Up to 3 years Tolerance of interventions considering any grade of 3 serious adverse events.
Incidence of new sepsis episodes At 3 years Incidence of new unscheduled hospitalizations At 3 years Incidence of sequels in neurocognitive, neuromuscular; cardiovascular, respiratory, renal, metabolic, and immune systems At 3 years