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

NCT06381661 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: APHP240385
• Study Type: interventional
• Target: 2,000
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Sepsis

Keywords

Sepsis; Platform trial; Precision Medicine

Outcome Measures

Primary Outcomes (2)

• All-cause mortality

  Dual primary endpoint

  At day 28

• Number of days alive without persistent life-supportive therapies

  Dual primary endpoint Respiratory support: high flow oxygen, non-invasive or invasive mechanical ventilation, extracorporeal membrane oxygenation or CO2 removal; cardiovascular support: continuous infusion of any dose of vasopressor or inotrope, or mechanical circulatory assistance; renal support: intermittent or continuous renal replacement therapy

  At day 28

Secondary Outcomes (29)

• Net benefit probability of intervention vs. control, assessed with a Generalized Pairwise Comparison (mortality prioritized over life-support-free days)

  At day 28

• Overall Survival

  At day 90

• Overall Survival

  At 1 year

• Overall Survival

  At 3 years

• Number of hospital free days

  At 1 year

Other Outcomes (10)

• Circulating levels of cytokines

  At inclusion

• Circulating levels of chemokines

  At inclusion

• Circulating levels of cytokines

  At day 1

Study Arms (24)

Hyperinflammation : Tocilizumab

EXPERIMENTAL

Drug: Tocilizumab

Hyperinflammation: Baricitinib

EXPERIMENTAL

Drug: Baricitinib

Hyperinflammation: Anakinra

EXPERIMENTAL

Drug: Anakinra

Hyperinflammation : blood purification with MTx.100 Plasma Adsorption Column

EXPERIMENTAL

Other: blood purification with MTx.100 Plasma Adsorption Column

Hyperinflammation : usual care

ACTIVE COMPARATOR

Other: Usual care

Hypoinflammation : G CSF filgrastim

EXPERIMENTAL

Drug: Heparin; Drug: G-CSF filgrastim

Hypoinflammation : Interferon gamma-1b

EXPERIMENTAL

Drug: Interferon gamma-1b

Hypoinflammation : usual care

ACTIVE COMPARATOR

Other: Usual care

MALS : Anakinra

EXPERIMENTAL

Drug: Anakinra

MALS : blood purification with MTx.100 Plasma Adsorption Column

EXPERIMENTAL

Other: blood purification with MTx.100 Plasma Adsorption Column

MALS : usual care

ACTIVE COMPARATOR

Other: Usual care

Corticoids response : Hydrocortisone

EXPERIMENTAL

Drug: Hydrocortisone

Corticoids response : Fludrocortisone

EXPERIMENTAL

Drug: Fludrocortisone

Corticoids response : Hydrocortisone + Fludrocortisone

EXPERIMENTAL

Drug: Hydrocortisone and fludrocortisone

Corticoids response : usual care

ACTIVE COMPARATOR

Other: Usual care

Hypercoagulation : Prophylactic unfractionated heparin (UFH)

EXPERIMENTAL

Drug: Prophylactic unfractionated heparin (UFH)

Hypercoagulation : Therapeutic UFH

EXPERIMENTAL

Drug: Heparin

Hypercoagulation : Therapeutic low molecular weight heparin (LMWH)

EXPERIMENTAL

Drug: Low molecular weight heparin

Hypercoagulation : Thrombomodulin

EXPERIMENTAL

Drug: Recombinant humanThrombomodulin( rhTM)

Hypercoagulation : usual care

ACTIVE COMPARATOR

Other: Usual care

Hypofrinolysis : Sivelestat

EXPERIMENTAL

Drug: Sivelestat

Hypofrinolysis : OctaplasLG

EXPERIMENTAL

Drug: Octaplas LG

Hypofrinolysis : Plasminogen

EXPERIMENTAL

Drug: Plasminogen

Hypofrinolysis : Usual care

ACTIVE COMPARATOR

Other: Usual care

Interventions

Tocilizumab DRUG

8 mg per kilogram of body weight enterally (oral or via a gastric tube) once daily for 14 days (or hospital discharge pending which will occur first) (same for adults and children)

Hyperinflammation : Tocilizumab

Baricitinib DRUG

4mg, enterally (oral or via a gastric tube) once daily for 14 days (or hospital discharge pending which will occur first) (same for adults and children)

Hyperinflammation: Baricitinib

Anakinra DRUG

100 mg subcutaneously once daily for 10 days (or hospital discharge pending which will occur first) (same for adults and children)

Hyperinflammation: Anakinra; MALS : Anakinra

Hydrocortisone DRUG

50mg (in children: 1-2 mg/kg) IV Q6 for 7 days

Corticoids response : Hydrocortisone

Hydrocortisone and fludrocortisone DRUG

Hydrocortisone 50mg IV Q6 for 7 days + Fludrocortisone 50mg orally or via gastric tube once a day for 7 days.

Corticoids response : Hydrocortisone + Fludrocortisone

Heparin DRUG

Therapeutic unfractionated heparin (UFH) starting at 400 (in children: 20 IU/kg/h) IU/kg/24h (target between 0.3 and 0.5 IU/ml), adapted to the therapeutic Partial Thromboplastin Time targeting values in the range of 60 to 100 seconds, with lower intensity dosing in the range of 60 to 80 seconds, for 7 days (or ICU discharge, pending which will occur first).

Hypercoagulation : Therapeutic UFH; Hypoinflammation : G CSF filgrastim

Low molecular weight heparin DRUG

Therapeutic low weight molecular heparin (LMWH) tinzaparin, considering its contraindications, recommended dose ranges and monitoring if applicable, as follows: 175 (in children 100 U/kg) IU/kg/24h, for 7 days (or hospital discharge pending which will occur first).

Hypercoagulation : Therapeutic low molecular weight heparin (LMWH)

Recombinant humanThrombomodulin( rhTM) DRUG

Recombinant human thrombomodulin (rhTM) 0.06 mg/kg/j IV, for 7 days (or ICU discharge, pending which will occur first).

Hypercoagulation : Thrombomodulin

Sivelestat DRUG

0.2 mg/kg/h for 7 days (or ICU discharge, pending which will occur first)

Hypofrinolysis : Sivelestat

Usual care OTHER

Usual care

Corticoids response : usual care; Hypercoagulation : usual care; Hyperinflammation : usual care; Hypofrinolysis : Usual care; Hypoinflammation : usual care; MALS : usual care

blood purification with MTx.100 Plasma Adsorption Column OTHER

up to 4 hours a day, up to four days in a row

Hyperinflammation : blood purification with MTx.100 Plasma Adsorption Column; MALS : blood purification with MTx.100 Plasma Adsorption Column

G-CSF filgrastim DRUG

0.5 MIU (5μg)/kg/day subcutaneously for 5 consecutive days (or up to ICU discharge pending which occurs first) - same for adults and children .

Hypoinflammation : G CSF filgrastim

Interferon gamma-1b DRUG

rhIFNg subcutaneously at 50 µg/m2 if body surface \>0,5 m2, or 1.5µg/kg if body surface of 0,5 m2or less, every other day for 15 days (or up to ICU discharge pending which occurs first)

Hypoinflammation : Interferon gamma-1b

Fludrocortisone DRUG

50µg orally (or via the gastric tube) once a day for 7 days (or ICU discharge pending which will occur first) (same for adults and children)

Corticoids response : Fludrocortisone

Prophylactic unfractionated heparin (UFH) DRUG

100 IU/kg/24h for 6 days

Hypercoagulation : Prophylactic unfractionated heparin (UFH)

Octaplas LG DRUG

12 mL/kg on day 1; repeated daily from day 2 to day 5, provided that PT/INR remains ≥ 1.40 (This intervention will be opened for randomisation once a supply circuit is in place)

Hypofrinolysis : OctaplasLG

Plasminogen DRUG

2,2 mg/kg/day (intravenous infusion) during 3 days.

Hypofrinolysis : Plasminogen

Eligibility Criteria

• Age: 37 Weeks+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Conditions

Sepsis

Interventions

tocilizumab; baricitinib; Interleukin 1 Receptor Antagonist Protein; Hydrocortisone; Fludrocortisone; Heparin; Heparin, Low-Molecular-Weight; sivelestat; interferon gamma-1b; Plasminogen

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Glycosaminoglycans; Polysaccharides; Carbohydrates; Enzyme Precursors; Enzymes and Coenzymes; Beta-Globulins; Serum Globulins; Blood Proteins; Globulins; Protein Precursors

Central Study Contacts

Djillali Annane, Pr

CONTACT

+33147107787; djillali.annane@aphp.fr

Jérôme Lambert

CONTACT

+33142499742; jerome.lambert@u-paris.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomization will concern 6 specific treatable traits (hyperinflammation, hypoinflammation, Macrophage Activation Like Syndrome, Corticoid response, hypercoagulation, Hypofibrinolysis). In each treatable trait, patients will be randomly allocated between control (usual care) and 1 to 4 experimental treatments using parallell arms.

Study Record Dates

• First Submitted: April 9, 2024
• First Posted: April 24, 2024
• Study Start: May 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): May 1, 2031
• Last Updated: January 27, 2026

Record last verified: 2026-01