SepsisPhase 2PALETTENCT06381661
Adaptive Platform Trial for Personnalisation of Sepsis Treatment in Children and Adults: a Multi-national, Treatable Traits-guided, Adaptive, Exploratory, Bayesian Basket Trial
A Phase 2 study testing Tocilizumab, Baricitinib and Anakinra in people with Sepsis, run by Assistance Publique - Hôpitaux de Paris at 19 sites in France.
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. Read more about this study
- Who is it for?
- Ages 37 weeks and older
- Conditions the study is for
- Sepsis
- What is being tested?
- Tocilizumab, Baricitinib and Anakinra
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,000 participants
- Where
- 19 sitesFrance
- Study dates
- 9 Jul 2026to 9 Jul 2031
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 37 weeks and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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:
- Documented or suspected infection,
- 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.
Trial locations and contacts
19 sites in 1 country. Contact the study team or a site near you to ask about taking part.
19 sites in 1 country
France19 sites, 19 recruiting
- Recruiting
CHU Dijon - infectiologie
Dijon
Lionel Piroth, 0380293305 ext. +33, lionel.piroth@chu-dijon.fr
- Recruiting
CHU Dijon - réanimation adulte
Dijon
Jean-Pierre Quenot, 0380293685 ext. +33, jean-pierre.quenot@chu-dijon.fr
- Not yet recruiting
CH Sud Essonne - site d'Etampes - Réanimation adulte
Étampes
Shidasp Siami, 01 60 80 79 40 ext. +33, shidasp.siami@ch-sudessonne.fr
- Recruiting
Hôpital Raymond Poincaré - infectiologie
Garches
Aurélien Dinh, 0147107760 ext. +33, aurelien.dinh@aphp.fr
- Recruiting
Hôpital Raymond Poincaré
Garches
Djillali Annane, MD PhD, 0147107787 ext. +33, djillali.annane@aphp.fr
- Recruiting
CH de Haguenau
Haguenau
Asael Berger, 03 88 06 30 63 ext. +33, Asael.BERGER@ch-haguenau.fr
- Recruiting
CHD Vendée - infectiologie
La Roche-sur-Yon
Thomas Guimard, 0251446385 ext. +33, thomas.guimard@ght85.fr
- Recruiting
CHD Vendée - réanimation adulte
La Roche-sur-Yon
Matthieu Henry, 0251446026 ext. +33, matthieu.henry@ght85.fr
- Not yet recruiting
CH Le Mans - Réanimation adulte
Le Mans
Christophe Guitton, 02 43 43 24 58 ext. +33, cguitton@ch-lemans.fr
- Recruiting
CHRU Nancy - Hôpital Central - Réanimation adulte
Nancy
Sébastien Gibot, 03 83 85 21 23 ext. +33, s.gibot@chru-nancy.fr
- Not yet recruiting
CHU Nantes - Hôpital Hôtel Dieu - Infectiologie
Nantes
Benjamin Gaborit, 02 44 76 82 92 ext. +33, Benjamin.GABORIT@chu-nantes.fr
- Not yet recruiting
CHU Nantes - Hôpital Hôtel Dieu - Réanimation adulte
Nantes
Jean Reigner, 02 40 08 73 65 ext. +33, jean.reignier@chu-nantes.fr
- Recruiting
AP-HP Hôpital Bichat - Réanimation adulte
Paris
Jean-François Timsit, 01 40 25 77 02 ext. +33, jean-francois.timsit@aphp.fr
- Not yet recruiting
AP-HP Hôpital Bicêtre - Infectiologie
Paris
Lélia Escaut, 01 45 21 74 26 ext. +33, lelia.escaut@aphp.fr
- Not yet recruiting
AP-HP Hôpital Bicêtre - Réanimation adulte
Paris
Xavier Monnet, 01 45 21 35 39 ext. +33, xavier.monnet@aphp.fr
- Recruiting
Hôpital Saint Antoine AP-HP - infectiologie
Paris
Karine Lacombe, 0149282438 ext. +33, karine.lacombe2@aphp.fr
- Recruiting
Hôpital Saint Antoine AP-HP - réanimation adulte
Paris
Jérémie Joffre, 0149282943 ext. +33, jeremie.joffre@aphp.fr
- Not yet recruiting
CHU Strasbourg - Hôpital Civil (NHC) - Réanimation adulte
Strasbourg
Julie Helms, 03 69 55 13 69 ext. +33, julie.helms@chru-strasbourg.fr
- Not yet recruiting
CH Tourcoing
Tourcoing
Olivier Robineau, 03 20 69 46 17 ext. +33, orobineau@ch-tourcoing.fr
About this study
Official title: 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.
- Conditions
- Sepsis
- Being tested
- Tocilizumab, Baricitinib, Anakinra, Hydrocortisone, Hydrocortisone and fludrocortisone
- Keywords
- Sepsis, Platform trial, Precision Medicine
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TocilizumabDrug
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)
BaricitinibDrug
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)
AnakinraDrug
100 mg subcutaneously once daily for 10 days (or hospital discharge pending which will occur first) (same for adults and children)
HydrocortisoneDrug
50mg (in children: 1-2 mg/kg) IV Q6 for 7 days
Hydrocortisone and fludrocortisoneDrug
Hydrocortisone 50mg IV Q6 for 7 days + Fludrocortisone 50mg orally or via gastric tube once a day for 7 days.
HeparinDrug
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 heparinDrug
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)Drug
Recombinant human thrombomodulin (rhTM) 0.06 mg/kg/j IV, for 7 days (or ICU discharge, pending which will occur first).
SivelestatDrug
0.2 mg/kg/h for 7 days (or ICU discharge, pending which will occur first)
Usual careOther
Usual care
blood purification with MTx.100 Plasma Adsorption ColumnOther
up to 4 hours a day, up to four days in a row
G-CSF filgrastimDrug
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 .
Interferon gamma-1bDrug
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)
FludrocortisoneDrug
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)
Prophylactic unfractionated heparin (UFH)Drug
100 IU/kg/24h for 6 days
Octaplas LGDrug
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)
PlasminogenDrug
2,2 mg/kg/day (intravenous infusion) during 3 days.
| Study group | Role | What they receive |
|---|---|---|
| Hyperinflammation : Tocilizumab | Experimental | Not described Receives: Drug: Tocilizumab |
| Hyperinflammation: Baricitinib | Experimental | Not described Receives: Drug: Baricitinib |
| Hyperinflammation: Anakinra | Experimental | Not described Receives: Drug: Anakinra |
| Hyperinflammation : blood purification with MTx.100 Plasma Adsorption Column | Experimental | Not described Receives: Other: blood purification with MTx.100 Plasma Adsorption Column |
| Hyperinflammation : usual care | Active comparator | Not described Receives: Other: Usual care |
| Hypoinflammation : G CSF filgrastim | Experimental | Not described Receives: Drug: Heparin; Drug: G-CSF filgrastim |
| Hypoinflammation : Interferon gamma-1b | Experimental | Not described Receives: Drug: Interferon gamma-1b |
| Hypoinflammation : usual care | Active comparator | Not described Receives: Other: Usual care |
| MALS : Anakinra | Experimental | Not described Receives: Drug: Anakinra |
| MALS : blood purification with MTx.100 Plasma Adsorption Column | Experimental | Not described Receives: Other: blood purification with MTx.100 Plasma Adsorption Column |
| MALS : usual care | Active comparator | Not described Receives: Other: Usual care |
| Corticoids response : Hydrocortisone | Experimental | Not described Receives: Drug: Hydrocortisone |
| Corticoids response : Fludrocortisone | Experimental | Not described Receives: Drug: Fludrocortisone |
| Corticoids response : Hydrocortisone + Fludrocortisone | Experimental | Not described Receives: Drug: Hydrocortisone and fludrocortisone |
| Corticoids response : usual care | Active comparator | Not described Receives: Other: Usual care |
| Hypercoagulation : Prophylactic unfractionated heparin (UFH) | Experimental | Not described Receives: Drug: Prophylactic unfractionated heparin (UFH) |
| Hypercoagulation : Therapeutic UFH | Experimental | Not described Receives: Drug: Heparin |
| Hypercoagulation : Therapeutic low molecular weight heparin (LMWH) | Experimental | Not described Receives: Drug: Low molecular weight heparin |
| Hypercoagulation : Thrombomodulin | Experimental | Not described Receives: Drug: Recombinant humanThrombomodulin( rhTM) |
| Hypercoagulation : usual care | Active comparator | Not described Receives: Other: Usual care |
| Hypofrinolysis : Sivelestat | Experimental | Not described Receives: Drug: Sivelestat |
| Hypofrinolysis : OctaplasLG | Experimental | Not described Receives: Drug: Octaplas LG |
| Hypofrinolysis : Plasminogen | Experimental | Not described Receives: Drug: Plasminogen |
| Hypofrinolysis : Usual care | Active comparator | Not described Receives: Other: Usual care |
What is being measured
The primary outcome is the main question the study is designed to answer.
All-cause mortality
Dual primary endpoint
Measured: 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
Measured: 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)
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.
Measured: At day 28
Overall Survival
Measured: At day 90
Overall Survival
Measured: At 1 year
Overall Survival
Measured: At 3 years
Number of hospital free days
Measured: At 1 year
Number of hospital free days
Measured: At 3 years
Time to recover walking
Measured: At day 90
Time to resume previous social and professional activities
Measured: 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.
Measured: 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.
Measured: At day 90
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: At 3 years
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.
Measured: 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.
Measured: At 3 years
Number of adverse events
Tolerance of interventions considering any grade of 3 serious adverse events.
Measured: Up to 3 years
Incidence of new sepsis episodes
Measured: At day 90
Incidence of new sepsis episodes
Measured: At 1 year
Incidence of new sepsis episodes
Measured: At 3 years
Incidence of new unscheduled hospitalizations
Measured: At day 90
Incidence of new unscheduled hospitalizations
Measured: At 1 year
Incidence of new unscheduled hospitalizations
Measured: At 3 years
Incidence of sequels in neurocognitive, neuromuscular; cardiovascular, respiratory, renal, metabolic, and immune systems
Measured: At 3 years
Number of grade 3 serious adverse events
Measured: At day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2024
- Study start9 Jul 2026
- Primary completion9 Aug 2028 (estimated)
- Study completion9 Jul 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 2,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06381661
- Sponsor's protocol ID
- APHP240385
- Acronym
- PALETTE
- Status last verified
- Aug 2026
- First submitted
- 9 Apr 2024
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided