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

Description

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.

Interventions

• Tocilizumab (Drug)
  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 (Drug)
  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 (Drug)
  100 mg subcutaneously once daily for 10 days (or hospital discharge pending which will occur first) (same for adults and children)
• Hydrocortisone (Drug)
  50mg (in children: 1-2 mg/kg) IV Q6 for 7 days
• Hydrocortisone and fludrocortisone (Drug)
  Hydrocortisone 50mg IV Q6 for 7 days + Fludrocortisone 50mg orally or via gastric tube once a day for 7 days.
• Heparin (Drug)
  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 (Drug)
  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).
• Sivelestat (Drug)
  0.2 mg/kg/h for 7 days (or ICU discharge, pending which will occur first)
• Usual care (Other)
  Usual care
• blood purification with MTx.100 Plasma Adsorption Column (Other)
  up to 4 hours a day, up to four days in a row
• G-CSF filgrastim (Drug)
  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-1b (Drug)
  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)
• Fludrocortisone (Drug)
  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 LG (Drug)
  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)
• Plasminogen (Drug)
  2,2 mg/kg/day (intravenous infusion) during 3 days.

Eligibility criteria

Conditions

Locations

• CHU Dijon - infectiologie — Dijon, France
• CHU Dijon - réanimation adulte — Dijon, France
• CH Sud Essonne - site d'Etampes - Réanimation adulte — Étampes, France
• Hôpital Raymond Poincaré - infectiologie — Garches, France
• Hôpital Raymond Poincaré — Garches, France
• CH de Haguenau — Haguenau, France
• CHD Vendée - infectiologie — La Roche-sur-Yon, France
• CHD Vendée - réanimation adulte — La Roche-sur-Yon, France
• CH Le Mans - Réanimation adulte — Le Mans, France
• CHRU Nancy - Hôpital Central - Réanimation adulte — Nancy, France
• CHU Nantes - Hôpital Hôtel Dieu - Infectiologie — Nantes, France
• CHU Nantes - Hôpital Hôtel Dieu - Réanimation adulte — Nantes, France
• AP-HP Hôpital Bichat - Réanimation adulte — Paris, France
• AP-HP Hôpital Bicêtre - Infectiologie — Paris, France
• AP-HP Hôpital Bicêtre - Réanimation adulte — Paris, France
• Hôpital Saint Antoine AP-HP - infectiologie — Paris, France
• Hôpital Saint Antoine AP-HP - réanimation adulte — Paris, France
• CHU Strasbourg - Hôpital Civil (NHC) - Réanimation adulte — Strasbourg, France
• CH Tourcoing — Tourcoing, France