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

Sepsis Clinical Trial

— PALETTE  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06381661
• Other study ID #: APHP240385
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: April 1, 2026
• Est. completion date: April 1, 2032

Study information

• Verified date: April 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Djillali Annane, Pr
• Phone: +33147107787
• Email: djillali.annane[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 2000
• Est. completion date: April 1, 2032
• Est. primary completion date: May 1, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 37 Weeks to 100 Years

Eligibility

Inclusion Criteria:

• All genders patients aged >37 weeks corrected gestational age with sepsis as per Sepsis-3 definition for adults, and as per the PHOENIX sepsis for children
• documented or suspected infection
• a Sequential Organ Failure Assessment (SOFA) score =2 for adults, and PHOENIX sepsis score of =2 for children.

Domain specific additional inclusion criteria :

1. Hyper or hypo inflammation based

• For adults on, respectively: beta, delta and gamma sub-phenotypes, and/or circulating levels of IL-6 > 100pg/mL, and lymphocytes counts < 1.0 × 109/L and/or HLA-DR <5,000 HLA-DR receptors/monocytes
• For children on: the PODIUM (+specific criteria for children)

2. Corticosteroids domain Corticosteroids responses based on the combination of Glucocorticoid-induced 1 GLCCI1) AA and nuclear factor (NF)-KB1 DI genotypes.

3. Coagulation domain

• Hypercoagulation state defined as a SIC score =4 points and neutrophils side fluorescence light (NEUT-SFL) >66 Arbitrary Units (patients with disseminated intravascular coagulopathy, DIC) or NEUT-SFL =66 AU (septic coagulopathy)
• Hypofibrinolytic state defined as SIC score =4 points and decreased plasminogen level <1.2 nM.

Exclusion Criteria:

• refused to consent participating in the study
• pregnancy
• any condition for which patient's primary physician will consider inappropriate enrolling patient in the study
• previous enrollment in the study.
• additional domain specific exclusion criteria relevant to specific interventions, i.e. tocilizumab, baricitinib, anakinra, hydrocortisone, fludrocortisone, unfractioned heparin, tinzaparin, human recombinant thrombomodulin, sivelestat, fresh frozen plasma, according to the "base de données publiques des medicaments" Patients can be included in multiple domains.

Related Conditions & MeSH terms

• Sepsis
• Toxemia

Intervention

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)
• 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)
• Anakinra
100 mg subcutaneously once daily for 10 days (or hospital discharge pending which will occur first) (same for adults and children)
• Hydrocortisone
50mg (in children: 1-2 mg/kg) IV Q6 for 7 days
• Hydrocortisone and fludrocortisone
Hydrocortisone 50mg IV Q6 for 7 days + Fludrocortisone 50mg orally or via gastric tube once a day for 7 days.
• 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).
• 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).
• Recombinant humanThrombomodulin( rhTM)
Recombinant human thrombomodulin (rhTM) 0.06 mg/kg/j IV, for 7 days (or ICU discharge, pending which will occur first).
• Sivelestat
0.2 mg/kg/h for 7 days (or ICU discharge, pending which will occur first)

Biological:
• Fresh frozen plasma
12 ml/kg/day as long as INR remains >1.4

Other:
• Usual care
Usual care

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-cause mortality		At day 28
Primary	Number of patients with persistent life-supportive therapies	Respiratory support: non-invasive, invasive mechanical ventilation; cardiovascular support: continuous infusion of any dose of vasopressor or inotrope; renal support: intermittent or continuous renal replacement therapy	At day 28
Secondary	Composite of the two primary outcomes	All deaths are scored "-1" on the ordinal scale, i.e., the worst outcome. Then to assess important changes in outcome for survivors, the number of days free of organ support up until day 28 is calculated, with higher score indicating faster recovery. Organ support is defined as needing either respiratory, cardiovascular or renal support. Respiratory support is defined as invasive mechanical ventilation or non-invasive ventilation including continuous positive airway pressure or high-flow nasal oxygen with an FiO2=0.4 and a flow rate =30L/min. Cardiovascular support is defined as ongoing infusion of any dose of any vasopressor or inotrope drug. Renal support is defined by the requirement of renal replacement therapy regardless of treatment modalities.	At day 28
Secondary	Overall Survival		At day 90
Secondary	Overall Survival		At 1 year
Secondary	Overall Survival		At 3 years
Secondary	Number of hospital free days		At 1 year
Secondary	Number of hospital free days		At 3 years
Secondary	Time to recover walking		At day 90
Secondary	Time to resume previous social and professional activities		At 1 year
Secondary	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
Secondary	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
Secondary	Quality of life score for children assessed by FFS	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
Secondary	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
Secondary	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
Secondary	Quality of life score for children assessed by FFS	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
Secondary	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
Secondary	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
Secondary	Quality of life score for children assessed by FFS	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
Secondary	Number of adverse events	Tolerance of interventions considering any grade of 3 serious adverse events.	Up to 3 years
Secondary	Incidence of new sepsis episodes		At day 90
Secondary	Incidence of new sepsis episodes		At 1 year
Secondary	Incidence of new sepsis episodes		At 3 years
Secondary	Incidence of new unscheduled hospitalizations		At day 90
Secondary	Incidence of new unscheduled hospitalizations		At 1 year
Secondary	Incidence of new unscheduled hospitalizations		At 3 years
Secondary	Incidence of sequels in neurocognitive, neuromuscular; cardiovascular, respiratory, renal, metabolic, and immune systems		At 3 years