Clinical trial NCT06381661: Adaptive Platform Trial for Personnalisation of Sepsis Treatment in Children and Adults: a Multi-national, Treatable Traits-guided, Adaptive, Bayesian Basket Trial
Official title: PALETTE- Adaptive Platform Trial for Personnalisation of Sepsis Treatment in Children and Adults: a Multi-national, Treatable Traits-guided, Adaptive, Bayesian Basket Trial"
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Sepsis
Keywords: Sepsis
Platform trial
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2024-04-24
Enrollment: 2000
Sex: ALL
Minimum age (years): 37
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomization will concern 3 specific domains (immunomodulation, coagulation, and corticosteroids); in each domain, patients will be randomly allocated between control (standard of care) and 1-4 experimental treatments using parallell arms
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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 :

1. 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)
2. Corticosteroids domain Corticosteroids responses based on the combination of Glucocorticoid-induced 1 GLCCI1) AA and nuclear factor (NF)-KB1 DI genotypes.
3. 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: All-cause mortality
timeFrame: At day 28
measure: Number of patients with persistent life-supportive therapies
timeFrame: At day 28
Secondary outcomes:
measure: Composite of the two primary outcomes
timeFrame: At day 28
measure: Overall Survival
timeFrame: At day 90
measure: Overall Survival
timeFrame: At 1 year
measure: Overall Survival
timeFrame: At 3 years
measure: Number of hospital free days
timeFrame: At 1 year
measure: Number of hospital free days
timeFrame: At 3 years
measure: Time to recover walking
timeFrame: At day 90
measure: Time to resume previous social and professional activities
timeFrame: At 1 year
measure: Quality of life score for adults assessed by SF-36
timeFrame: At day 90
measure: Quality of life score for adults assessed by EQ-5D-5L
timeFrame: At day 90
measure: Quality of life score for children assessed by FFS
timeFrame: At day 90
measure: Quality of life score for adults assessed by SF-36
timeFrame: At 1 year
measure: Quality of life score for adults assessed by EQ-5D-5L
timeFrame: At 1 year
measure: Quality of life score for children assessed by FFS
timeFrame: At 1 year
measure: Quality of life score for adults assessed by SF-36
timeFrame: At 3 years
measure: Quality of life score for adults assessed by EQ-5D-5L
timeFrame: At 3 years
measure: Quality of life score for children assessed by FFS
timeFrame: At 3 years
measure: Number of adverse events
timeFrame: Up to 3 years
measure: Incidence of new sepsis episodes
timeFrame: At day 90
measure: Incidence of new sepsis episodes
timeFrame: At 1 year
measure: Incidence of new sepsis episodes
timeFrame: At 3 years
measure: Incidence of new unscheduled hospitalizations
timeFrame: At day 90
measure: Incidence of new unscheduled hospitalizations
timeFrame: At 1 year
measure: Incidence of new unscheduled hospitalizations
timeFrame: At 3 years
measure: Incidence of sequels in neurocognitive, neuromuscular; cardiovascular, respiratory, renal, metabolic, and immune systems
timeFrame: At 3 years
Other outcomes:
Locations:
Study officials:
References: