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

Официальное название

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

Обзор

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.

Вмешательства

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

Первичные конечные точки

• All-cause mortality [Срок оценки: At day 28]
• Number of days alive without persistent life-supportive therapies [Срок оценки: At day 28]

Вторичные конечные точки (12)

• Net benefit probability of intervention vs. control, assessed with a Generalized Pairwise Comparison (mortality prioritized over life-support-free days) [Срок оценки: At day 28]
• Overall Survival [Срок оценки: At day 90]
• Overall Survival [Срок оценки: At 1 year]
• Overall Survival [Срок оценки: At 3 years]
• Number of hospital free days [Срок оценки: At 1 year]
• Number of hospital free days [Срок оценки: At 3 years]
• Time to recover walking [Срок оценки: At day 90]
• Time to resume previous social and professional activities [Срок оценки: At 1 year]
• Quality of life score for adults assessed by SF-36 [Срок оценки: At day 90]
• Quality of life score for adults assessed by EQ-5D-5L [Срок оценки: At day 90]
• Pediatric Quality of Life Inventory (PedsQL) [Срок оценки: At day 90]
• Quality of life score for children assessed by FSS [Срок оценки: At day 90]

Критерии участия

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT06381661 · APHP240385

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗