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

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

Interventions

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)

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)

DRUG

Anakinra

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

DRUG

Hydrocortisone

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

DRUG

Hydrocortisone and fludrocortisone

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

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

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).

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).

DRUG

Sivelestat

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

OTHER

Usual care

Usual care

OTHER

blood purification with MTx.100 Plasma Adsorption Column

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

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 .

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)

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)

DRUG

Prophylactic unfractionated heparin (UFH)

100 IU/kg/24h for 6 days

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)

DRUG

Plasminogen

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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

37 Weeks

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-05-01

Primary Completion

2028-06-01

Completion

2031-05-01