PALETTE- Adaptive Platform Trial for Personnalisation of Sepsis Treatment in Children and Adults: a Multi-national, Treatable Traits-guided, Adaptive, Exploratory, Bayesian Basket Trial
概览
- 阶段
- 2 期
- 干预措施
- Usual care
- 疾病 / 适应症
- Sepsis
- 发起方
- Assistance Publique - Hôpitaux de Paris
- 入组人数
- 2000
- 主要终点
- All-cause mortality
- 状态
- 尚未招募
- 最后更新
- 3个月前
概览
简要总结
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.
研究者
入排标准
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Corticoids response : usual care
干预措施: Usual care
Hypercoagulation : Prophylactic unfractionated heparin (UFH)
干预措施: Prophylactic unfractionated heparin (UFH)
Hyperinflammation : usual care
干预措施: Usual care
Hypoinflammation : G CSF filgrastim
干预措施: Heparin
Hypoinflammation : G CSF filgrastim
干预措施: G-CSF filgrastim
Corticoids response : Hydrocortisone
干预措施: Hydrocortisone
Hypoinflammation : Interferon gamma-1b
干预措施: Interferon gamma-1b
Hypoinflammation : usual care
干预措施: Usual care
MALS : Anakinra
干预措施: Anakinra
MALS : blood purification with MTx.100 Plasma Adsorption Column
干预措施: blood purification with MTx.100 Plasma Adsorption Column
MALS : usual care
干预措施: Usual care
Hyperinflammation : Tocilizumab
干预措施: Tocilizumab
Hyperinflammation: Baricitinib
干预措施: Baricitinib
Hyperinflammation: Anakinra
干预措施: Anakinra
Hyperinflammation : blood purification with MTx.100 Plasma Adsorption Column
干预措施: blood purification with MTx.100 Plasma Adsorption Column
Corticoids response : Fludrocortisone
干预措施: Fludrocortisone
Corticoids response : Hydrocortisone + Fludrocortisone
干预措施: Hydrocortisone and fludrocortisone
Hypercoagulation : Therapeutic UFH
干预措施: Heparin
Hypercoagulation : Therapeutic low molecular weight heparin (LMWH)
干预措施: Low molecular weight heparin
Hypercoagulation : Thrombomodulin
干预措施: Recombinant humanThrombomodulin( rhTM)
Hypercoagulation : usual care
干预措施: Usual care
Hypofrinolysis : Sivelestat
干预措施: Sivelestat
Hypofrinolysis : OctaplasLG
干预措施: Octaplas LG
Hypofrinolysis : Plasminogen
干预措施: Plasminogen
Hypofrinolysis : Usual care
干预措施: Usual care
结局指标
主要结局
All-cause mortality
时间窗: At day 28
Dual primary endpoint
Number of days alive without persistent life-supportive therapies
时间窗: At day 28
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
次要结局
- Time to recover walking(At day 90)
- Time to resume previous social and professional activities(At 1 year)
- Overall Survival(At 3 years)
- Number of hospital free days(At 3 years)
- Quality of life score for adults assessed by SF-36(At 3 years)
- Quality of life score for adults assessed by EQ-5D-5L(At 3 years)
- Number of adverse events(Up to 3 years)
- Incidence of new sepsis episodes(At 3 years)
- 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)(At day 28)
- Overall Survival(At day 90)
- Overall Survival(At 1 year)
- Number of hospital free days(At 1 year)
- Quality of life score for adults assessed by SF-36(At day 90)
- Quality of life score for adults assessed by EQ-5D-5L(At day 90)
- Pediatric Quality of Life Inventory (PedsQL)(At day 90)
- Quality of life score for children assessed by FSS(At day 90)
- Quality of life score for adults assessed by SF-36(At 1 year)
- Quality of life score for adults assessed by EQ-5D-5L(At 1 year)
- Quality of life score for children assessed by FSS(At 1 year)
- Pediatric Quality of Life Inventory (PedsQL)(At 1 year)
- Quality of life score for children assessed by FSS(At 3 years)
- Pediatric Quality of Life Inventory (PedsQL)(At 3 years)
- Incidence of new sepsis episodes(At day 90)
- Incidence of new sepsis episodes(At 1 year)
- Incidence of new unscheduled hospitalizations(At day 90)
- Incidence of new unscheduled hospitalizations(At 1 year)
- Number of grade 3 serious adverse events(At day 28)