Adaptive Platform Trial for Personnalisation of Sepsis Treatment in Children and Adults: a Multi-national, Treatable Traits-guided, Adaptive, Exploratory, Bayesian Basket Trial (PALETTE)

Assistance Publique - Hôpitaux de Paris

Status and phase: Begins enrollment in 2 months; Phase 2

Conditions: Sepsis

Treatments: Drug: Heparin; Drug: Fludrocortisone; Drug: Anakinra; Drug: Plasminogen; Drug: Baricitinib; Drug: Tocilizumab; Drug: Prophylactic unfractionated heparin (UFH); Other: blood purification with MTx.100 Plasma Adsorption Column; Drug: Hydrocortisone and fludrocortisone; Other: Usual care; Drug: Sivelestat; Drug: Hydrocortisone; Drug: Interferon gamma-1b; Drug: Low molecular weight heparin; Drug: Octaplas LG; Drug: G-CSF filgrastim; Drug: Recombinant humanThrombomodulin( rhTM)

Study type: Interventional

Funder types: Other

Identifiers

NCT06381661

APHP240385

Details and patient eligibility

About

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.

Enrollment: 2,000 estimated patients

Sex: All

Ages: 37 weeks to 100 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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:

1. Documented or suspected infection,

2. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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2,000 participants in 24 patient groups

Hyperinflammation : Tocilizumab

Experimental group

Treatment:

Drug: Tocilizumab

Hyperinflammation: Baricitinib

Experimental group

Treatment:

Drug: Baricitinib

Hyperinflammation: Anakinra

Experimental group

Treatment:

Drug: Anakinra

Hyperinflammation : blood purification with MTx.100 Plasma Adsorption Column

Experimental group

Treatment:

Other: blood purification with MTx.100 Plasma Adsorption Column

Hyperinflammation : usual care

Active Comparator group

Treatment:

Other: Usual care

Hypoinflammation : G CSF filgrastim

Experimental group

Treatment:

Drug: G-CSF filgrastim

Drug: Heparin

Hypoinflammation : Interferon gamma-1b

Experimental group

Treatment:

Drug: Interferon gamma-1b

Hypoinflammation : usual care

Active Comparator group

Treatment:

Other: Usual care

MALS : Anakinra

Experimental group

Treatment:

Drug: Anakinra

MALS : blood purification with MTx.100 Plasma Adsorption Column

Experimental group

Treatment:

Other: blood purification with MTx.100 Plasma Adsorption Column

MALS : usual care

Active Comparator group

Treatment:

Other: Usual care

Corticoids response : Hydrocortisone

Experimental group

Treatment:

Drug: Hydrocortisone

Corticoids response : Fludrocortisone

Experimental group

Treatment:

Drug: Fludrocortisone

Corticoids response : Hydrocortisone + Fludrocortisone

Experimental group

Treatment:

Drug: Hydrocortisone and fludrocortisone

Corticoids response : usual care

Active Comparator group

Treatment:

Other: Usual care

Hypercoagulation : Prophylactic unfractionated heparin (UFH)

Experimental group

Treatment:

Drug: Prophylactic unfractionated heparin (UFH)

Hypercoagulation : Therapeutic UFH

Experimental group

Treatment:

Drug: Heparin

Hypercoagulation : Therapeutic low molecular weight heparin (LMWH)

Experimental group

Treatment:

Drug: Low molecular weight heparin

Hypercoagulation : Thrombomodulin

Experimental group

Treatment:

Drug: Recombinant humanThrombomodulin( rhTM)

Hypercoagulation : usual care

Active Comparator group

Treatment:

Other: Usual care

Hypofrinolysis : Sivelestat

Experimental group

Treatment:

Drug: Sivelestat

Hypofrinolysis : OctaplasLG

Experimental group

Treatment:

Drug: Octaplas LG

Hypofrinolysis : Plasminogen

Experimental group

Treatment:

Drug: Plasminogen

Hypofrinolysis : Usual care

Active Comparator group

Treatment:

Other: Usual care