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

NCT ID: NCT06381661

Last Updated: 2026-01-27

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 2000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-05-01
• Study Completion Date: 2031-05-01

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MALS : blood purification with MTx.100 Plasma Adsorption Column

Group Type: EXPERIMENTAL

blood purification with MTx.100 Plasma Adsorption Column

Intervention Type: OTHER

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

MALS : usual care

Group Type: ACTIVE_COMPARATOR

Usual care

Intervention Type: OTHER

Usual care

Corticoids response : Hydrocortisone

Group Type: EXPERIMENTAL

Hydrocortisone

Intervention Type: DRUG

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

Corticoids response : Fludrocortisone

Group Type: EXPERIMENTAL

Fludrocortisone

Intervention Type: 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 : Hydrocortisone + Fludrocortisone

Group Type: EXPERIMENTAL

Hydrocortisone and fludrocortisone

Intervention Type: DRUG

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

Corticoids response : usual care

Group Type: ACTIVE_COMPARATOR

Usual care

Intervention Type: OTHER

Usual care

Hypercoagulation : Prophylactic unfractionated heparin (UFH)

Group Type: EXPERIMENTAL

Prophylactic unfractionated heparin (UFH)

Intervention Type: DRUG

100 IU/kg/24h for 6 days

Hypercoagulation : Therapeutic UFH

Group Type: EXPERIMENTAL

Heparin

Intervention Type: 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 low molecular weight heparin (LMWH)

Group Type: EXPERIMENTAL

Low molecular weight heparin

Intervention Type: 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 : Thrombomodulin

Group Type: EXPERIMENTAL

Recombinant humanThrombomodulin( rhTM)

Intervention Type: DRUG

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

Hypercoagulation : usual care

Group Type: ACTIVE_COMPARATOR

Usual care

Intervention Type: OTHER

Usual care

Hypofrinolysis : Sivelestat

Group Type: EXPERIMENTAL

Sivelestat

Intervention Type: DRUG

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

Hypofrinolysis : OctaplasLG

Group Type: EXPERIMENTAL

Octaplas LG

Intervention Type: 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 : Plasminogen

Group Type: EXPERIMENTAL

Plasminogen

Intervention Type: DRUG

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

Hypofrinolysis : Usual care

Group Type: ACTIVE_COMPARATOR

Usual care

Intervention Type: OTHER

Usual care

Hyperinflammation : Tocilizumab

Group Type: EXPERIMENTAL

Tocilizumab

Intervention Type: 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: Baricitinib

Group Type: EXPERIMENTAL

Baricitinib

Intervention Type: 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: Anakinra

Group Type: EXPERIMENTAL

Anakinra

Intervention Type: DRUG

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

Hyperinflammation : blood purification with MTx.100 Plasma Adsorption Column

Group Type: EXPERIMENTAL

blood purification with MTx.100 Plasma Adsorption Column

Intervention Type: OTHER

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

Hyperinflammation : usual care

Group Type: ACTIVE_COMPARATOR

Usual care

Intervention Type: OTHER

Usual care

Hypoinflammation : G CSF filgrastim

Group Type: EXPERIMENTAL

Heparin

Intervention Type: 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).

G-CSF filgrastim

Intervention Type: 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 : Interferon gamma-1b

Group Type: EXPERIMENTAL

Interferon gamma-1b

Intervention Type: 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 : usual care

Group Type: ACTIVE_COMPARATOR

Usual care

Intervention Type: OTHER

Usual care

MALS : Anakinra

Group Type: EXPERIMENTAL

Anakinra

Intervention Type: DRUG

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

Interventions

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)

Intervention Type: 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)

Intervention Type: DRUG

Anakinra

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

Intervention Type: DRUG

Hydrocortisone

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

Intervention Type: DRUG

Hydrocortisone and fludrocortisone

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

Intervention Type: 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).

Intervention Type: 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).

Intervention Type: 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).

Intervention Type: DRUG

Sivelestat

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

Intervention Type: DRUG

Usual care

Usual care

Intervention Type: OTHER

blood purification with MTx.100 Plasma Adsorption Column

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

Intervention Type: OTHER

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 .

Intervention Type: 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)

Intervention Type: 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)

Intervention Type: DRUG

Prophylactic unfractionated heparin (UFH)

100 IU/kg/24h for 6 days

Intervention Type: 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)

Intervention Type: DRUG

Plasminogen

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• 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

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

• Minimum Eligible Age: 37 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Central Contacts

Djillali Annane, Pr

Role: CONTACT

djillali.annane@aphp.fr

+33147107787

Jérôme Lambert

Role: CONTACT

jerome.lambert@u-paris.fr

+33142499742

Other Identifiers

APHP240385

Identifier Type: -

Identifier Source: org_study_id