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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis
• Intervention / Treatment: Other: Usual care; Drug: Tocilizumab; Drug: Baricitinib; Drug: Anakinra; Drug: Hydrocortisone; Drug: Hydrocortisone and fludrocortisone; Drug: Heparin; Drug: Low molecular weight heparin; Drug: Recombinant humanThrombomodulin( rhTM); Drug: Sivelestat; Other: blood purification with MTx.100 Plasma Adsorption Column; Drug: G-CSF filgrastim; Drug: Interferon gamma-1b; Drug: Fludrocortisone; Drug: Prophylactic unfractionated heparin (UFH); Drug: Octaplas LG; Drug: Plasminogen

• Study Type: Interventional
• Enrollment (Estimated): 2000
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Djillali Annane, Pr; Phone Number: +33147107787; Email: djillali.annane@aphp.fr
• Study Contact Backup: Name: Jérôme Lambert; Phone Number: +33142499742; Email: jerome.lambert@u-paris.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

24

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hyperinflammation : Tocilizumab	Drug: Tocilizumab; 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)
Experimental: Hyperinflammation: Baricitinib	Drug: Baricitinib; 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)
Experimental: Hyperinflammation: Anakinra	Drug: Anakinra; 100 mg subcutaneously once daily for 10 days (or hospital discharge pending which will occur first) (same for adults and children)
Experimental: Hyperinflammation : blood purification with MTx.100 Plasma Adsorption Column	Other: blood purification with MTx.100 Plasma Adsorption Column; up to 4 hours a day, up to four days in a row
Active Comparator: Hyperinflammation : usual care	Other: Usual care; Usual care
Experimental: Hypoinflammation : G CSF filgrastim	Drug: Heparin; 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).; Drug: G-CSF filgrastim; 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 .
Experimental: Hypoinflammation : Interferon gamma-1b	Drug: Interferon gamma-1b; 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)
Active Comparator: Hypoinflammation : usual care	Other: Usual care; Usual care
Experimental: MALS : Anakinra	Drug: Anakinra; 100 mg subcutaneously once daily for 10 days (or hospital discharge pending which will occur first) (same for adults and children)
Experimental: MALS : blood purification with MTx.100 Plasma Adsorption Column	Other: blood purification with MTx.100 Plasma Adsorption Column; up to 4 hours a day, up to four days in a row
Active Comparator: MALS : usual care	Other: Usual care; Usual care
Experimental: Corticoids response : Hydrocortisone	Drug: Hydrocortisone; 50mg (in children: 1-2 mg/kg) IV Q6 for 7 days
Experimental: Corticoids response : Fludrocortisone	Drug: Fludrocortisone; 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)
Experimental: Corticoids response : Hydrocortisone + Fludrocortisone	Drug: Hydrocortisone and fludrocortisone; Hydrocortisone 50mg IV Q6 for 7 days + Fludrocortisone 50mg orally or via gastric tube once a day for 7 days.
Active Comparator: Corticoids response : usual care	Other: Usual care; Usual care
Experimental: Hypercoagulation : Prophylactic unfractionated heparin (UFH)	Drug: Prophylactic unfractionated heparin (UFH); 100 IU/kg/24h for 6 days
Experimental: Hypercoagulation : Therapeutic UFH	Drug: Heparin; 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).
Experimental: Hypercoagulation : Therapeutic low molecular weight heparin (LMWH)	Drug: Low molecular weight heparin; 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).
Experimental: Hypercoagulation : Thrombomodulin	Drug: Recombinant humanThrombomodulin( rhTM); Recombinant human thrombomodulin (rhTM) 0.06 mg/kg/j IV, for 7 days (or ICU discharge, pending which will occur first).
Active Comparator: Hypercoagulation : usual care	Other: Usual care; Usual care
Experimental: Hypofrinolysis : Sivelestat	Drug: Sivelestat; 0.2 mg/kg/h for 7 days (or ICU discharge, pending which will occur first)
Experimental: Hypofrinolysis : OctaplasLG	Drug: Octaplas LG; 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)
Experimental: Hypofrinolysis : Plasminogen	Drug: Plasminogen; 2,2 mg/kg/day (intravenous infusion) during 3 days.
Active Comparator: Hypofrinolysis : Usual care	Other: Usual care; Usual care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival		At day 90
Overall Survival		At 1 year
Overall Survival		At 3 years
Number of hospital free days		At 1 year
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	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.	At day 90
Quality of life score for adults assessed by EQ-5D-5L	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.	At day 90
Quality of life score for adults assessed by SF-36	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.	At 1 year
Quality of life score for adults assessed by EQ-5D-5L	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.	At 1 year
Quality of life score for adults assessed by SF-36	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.	At 3 years
Quality of life score for adults assessed by EQ-5D-5L	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.	At 3 years
Number of adverse events	Tolerance of interventions considering any grade of 3 serious adverse events.	Up to 3 years
Incidence of new sepsis episodes		At day 90
Incidence of new sepsis episodes		At 1 year
Incidence of new sepsis episodes		At 3 years
Incidence of new unscheduled hospitalizations		At day 90
Incidence of new unscheduled hospitalizations		At 1 year
Incidence of new unscheduled hospitalizations		At 3 years
Incidence of sequels in neurocognitive, neuromuscular; cardiovascular, respiratory, renal, metabolic, and immune systems		At 3 years
Net benefit probability of intervention vs. control, assessed with a Generalized Pairwise Comparison (mortality prioritized over life-support-free days)	The Generalized Pairwise Comparison (GPC) method will be used to derive a single composite outcome. Each patient in the intervention group will be compared to each patient in the control group. For each pair, a score of +1, -1, or 0 will be assigned according to prioritized outcomes: (1) all-cause mortality at day 28, and (2) number of days alive without life-supportive therapies at day 28 if both patients have the same mortality status. The net benefit will be calculated as the sum of all pairwise scores divided by the total number of pairs, corresponding to the probability that a randomly chosen patient has a better outcome in one group than in the other.	At day 28
Pediatric Quality of Life Inventory (PedsQL)	Standardized tool used to measure health-related quality of life (HRQoL) in children and adolescents (ages 2-18) It is a 23-item score divided in four domains : Phtsical functioning, Emotional functioning, Social functioning, School functioning The total score vary from 0 to 100. The higher the score the hiher the quality of life.	At day 90
Quality of life score for children assessed by FSS	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.	At day 90
Quality of life score for children assessed by FSS	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.	At 1 year
Pediatric Quality of Life Inventory (PedsQL)	Standardized tool used to measure health-related quality of life (HRQoL) in children and adolescents (ages 2-18) It is a 23-item score divided in four domains : Phtsical functioning, Emotional functioning, Social functioning, School functioning The total score vary from 0 to 100. The higher the score the hiher the quality of life.	At 1 year
Quality of life score for children assessed by FSS	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.	At 3 years
Pediatric Quality of Life Inventory (PedsQL)	Standardized tool used to measure health-related quality of life (HRQoL) in children and adolescents (ages 2-18) It is a 23-item score divided in four domains : Phtsical functioning, Emotional functioning, Social functioning, School functioning The total score vary from 0 to 100. The higher the score the hiher the quality of life.	At 3 years
Number of grade 3 serious adverse events		At day 28

Other Outcome Measures

Outcome Measure	Time Frame
Circulating levels of cytokines	At inclusion
Circulating levels of chemokines	At inclusion
Circulating levels of cytokines	At day 1
Circulating levels of chemokines	At day 1
Circulating levels of cytokines	At day 7
Circulating levels of chemokines	At day 7
Circulating levels of cytokines	At 1 year
Circulating levels of chemokines	At 1 year
Circulating levels of cytokines	At 3 years
Circulating levels of chemokines	At 3 years

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): May 1, 2031

Study Registration Dates

• First Submitted: April 9, 2024
• First Submitted That Met QC Criteria: April 19, 2024
• First Posted (Actual): April 24, 2024

Study Record Updates

• Last Update Posted (Actual): January 27, 2026
• Last Update Submitted That Met QC Criteria: January 23, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Sepsis; Precision Medicine; Platform trial
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathological Conditions, Signs and Symptoms; Sepsis; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Carbohydrates; Polycyclic Compounds; Enzymes and Coenzymes; Blood Proteins; Serum Globulins; Globulins; Pregnanes; Steroids; Fused-Ring Compounds; Intercellular Signaling Peptides and Proteins; Glycosaminoglycans; Polysaccharides; Beta-Globulins; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; 17-Hydroxycorticosteroids; Cytokines; Enzyme Precursors; Protein Precursors; Hydrocortisone; Interleukin 1 Receptor Antagonist Protein; Fludrocortisone; Heparin; Heparin, Low-Molecular-Weight; Plasminogen; tocilizumab; baricitinib; interferon gamma-1b; sivelestat
• Other Study ID Numbers: APHP240385

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No