Ignite Creation Date:
2025-12-24 @ 1:06 PM
Ignite Modification Date:
2025-12-29 @ 12:35 PM
Study NCT ID:
NCT06381661
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-04-24
First Post:
2024-04-09
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Adaptive Platform Trial for Personnalisation of Sepsis Treatment in Children and Adults: a Multi-national, Treatable Traits-guided, Adaptive, Bayesian Basket Trial
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D018805', 'term': 'Sepsis'}], 'ancestors': [{'id': 'D007239', 'term': 'Infections'}, {'id': 'D018746', 'term': 'Systemic Inflammatory Response Syndrome'}, {'id': 'D007249', 'term': 'Inflammation'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C502936', 'term': 'tocilizumab'}, {'id': 'C000596027', 'term': 'baricitinib'}, {'id': 'D053590', 'term': 'Interleukin 1 Receptor Antagonist Protein'}, {'id': 'D006854', 'term': 'Hydrocortisone'}, {'id': 'D005438', 'term': 'Fludrocortisone'}, {'id': 'D006493', 'term': 'Heparin'}, {'id': 'D006495', 'term': 'Heparin, Low-Molecular-Weight'}, {'id': 'C069195', 'term': 'sivelestat'}], 'ancestors': [{'id': 'D016207', 'term': 'Cytokines'}, {'id': 'D036341', 'term': 'Intercellular Signaling Peptides and Proteins'}, {'id': 'D010455', 'term': 'Peptides'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D001685', 'term': 'Biological Factors'}, {'id': 'D011282', 'term': 'Pregnenediones'}, {'id': 'D011283', 'term': 'Pregnenes'}, {'id': 'D011278', 'term': 'Pregnanes'}, {'id': 'D013256', 'term': 'Steroids'}, {'id': 'D000072473', 'term': 'Fused-Ring Compounds'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D015062', 'term': '11-Hydroxycorticosteroids'}, {'id': 'D006889', 'term': 'Hydroxycorticosteroids'}, {'id': 'D000305', 'term': 'Adrenal Cortex Hormones'}, {'id': 'D006728', 'term': 'Hormones'}, {'id': 'D006730', 'term': 'Hormones, Hormone Substitutes, and Hormone Antagonists'}, {'id': 'D015065', 'term': '17-Hydroxycorticosteroids'}, {'id': 'D006025', 'term': 'Glycosaminoglycans'}, {'id': 'D011134', 'term': 'Polysaccharides'}, {'id': 'D002241', 'term': 'Carbohydrates'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Randomization will concern 3 specific domains (immunomodulation, coagulation, and corticosteroids); in each domain, patients will be randomly allocated between control (standard of care) and 1-4 experimental treatments using parallell arms'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 2000}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-04-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-04', 'completionDateStruct': {'date': '2032-04-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-04-19', 'studyFirstSubmitDate': '2024-04-09', 'studyFirstSubmitQcDate': '2024-04-19', 'lastUpdatePostDateStruct': {'date': '2024-04-24', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2024-04-24', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2029-05-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'All-cause mortality', 'timeFrame': 'At day 28'}, {'measure': 'Number of patients with persistent life-supportive therapies', 'timeFrame': 'At day 28', 'description': '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'}], 'secondaryOutcomes': [{'measure': 'Composite of the two primary outcomes', 'timeFrame': 'At day 28', 'description': '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.'}, {'measure': 'Overall Survival', 'timeFrame': 'At day 90'}, {'measure': 'Overall Survival', 'timeFrame': 'At 1 year'}, {'measure': 'Overall Survival', 'timeFrame': 'At 3 years'}, {'measure': 'Number of hospital free days', 'timeFrame': 'At 1 year'}, {'measure': 'Number of hospital free days', 'timeFrame': 'At 3 years'}, {'measure': 'Time to recover walking', 'timeFrame': 'At day 90'}, {'measure': 'Time to resume previous social and professional activities', 'timeFrame': 'At 1 year'}, {'measure': 'Quality of life score for adults assessed by SF-36', 'timeFrame': 'At day 90', 'description': '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.\n\nWare 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.'}, {'measure': 'Quality of life score for adults assessed by EQ-5D-5L', 'timeFrame': 'At day 90', 'description': '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.'}, {'measure': 'Quality of life score for children assessed by FFS', 'timeFrame': 'At day 90', 'description': '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.'}, {'measure': 'Quality of life score for adults assessed by SF-36', 'timeFrame': 'At 1 year', 'description': '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.\n\nWare 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.'}, {'measure': 'Quality of life score for adults assessed by EQ-5D-5L', 'timeFrame': 'At 1 year', 'description': '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.'}, {'measure': 'Quality of life score for children assessed by FFS', 'timeFrame': 'At 1 year', 'description': '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.'}, {'measure': 'Quality of life score for adults assessed by SF-36', 'timeFrame': 'At 3 years', 'description': '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.\n\nWare 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.'}, {'measure': 'Quality of life score for adults assessed by EQ-5D-5L', 'timeFrame': 'At 3 years', 'description': '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.'}, {'measure': 'Quality of life score for children assessed by FFS', 'timeFrame': 'At 3 years', 'description': '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.'}, {'measure': 'Number of adverse events', 'timeFrame': 'Up to 3 years', 'description': 'Tolerance of interventions considering any grade of 3 serious adverse events.'}, {'measure': 'Incidence of new sepsis episodes', 'timeFrame': 'At day 90'}, {'measure': 'Incidence of new sepsis episodes', 'timeFrame': 'At 1 year'}, {'measure': 'Incidence of new sepsis episodes', 'timeFrame': 'At 3 years'}, {'measure': 'Incidence of new unscheduled hospitalizations', 'timeFrame': 'At day 90'}, {'measure': 'Incidence of new unscheduled hospitalizations', 'timeFrame': 'At 1 year'}, {'measure': 'Incidence of new unscheduled hospitalizations', 'timeFrame': 'At 3 years'}, {'measure': 'Incidence of sequels in neurocognitive, neuromuscular; cardiovascular, respiratory, renal, metabolic, and immune systems', 'timeFrame': 'At 3 years'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Sepsis', 'Platform trial'], 'conditions': ['Sepsis']}, 'descriptionModule': {'briefSummary': "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."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'maximumAge': '100 Years', 'minimumAge': '37 Weeks', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* 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\n* documented or suspected infection\n* a Sequential Organ Failure Assessment (SOFA) score ≥2 for adults, and PHOENIX sepsis score of ≥2 for children.\n\nDomain specific additional inclusion criteria :\n\n1. Hyper or hypo inflammation based\n\n * 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\n * For children on: the PODIUM (+specific criteria for children)\n2. Corticosteroids domain Corticosteroids responses based on the combination of Glucocorticoid-induced 1 GLCCI1) AA and nuclear factor (NF)-KB1 DI genotypes.\n3. Coagulation domain\n\n * 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)\n * Hypofibrinolytic state defined as SIC score ≥4 points and decreased plasminogen level \\<1.2 nM.\n\nExclusion Criteria:\n\n* refused to consent participating in the study\n* pregnancy\n* any condition for which patient\'s primary physician will consider inappropriate enrolling patient in the study\n* previous enrollment in the study.\n* 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"\n\nPatients can be included in multiple domains.'}, 'identificationModule': {'nctId': 'NCT06381661', 'acronym': 'PALETTE', 'briefTitle': 'Adaptive Platform Trial for Personnalisation of Sepsis Treatment in Children and Adults: a Multi-national, Treatable Traits-guided, Adaptive, Bayesian Basket Trial', 'organization': {'class': 'OTHER', 'fullName': 'Assistance Publique - Hôpitaux de Paris'}, 'officialTitle': 'PALETTE- Adaptive Platform Trial for Personnalisation of Sepsis Treatment in Children and Adults: a Multi-national, Treatable Traits-guided, Adaptive, Bayesian Basket Trial"', 'orgStudyIdInfo': {'id': 'APHP240385'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Immuno-modulation : Tocilizumab', 'interventionNames': ['Drug: Tocilizumab']}, {'type': 'EXPERIMENTAL', 'label': 'Immuno-modulation Baricitinib', 'interventionNames': ['Drug: Baricitinib']}, {'type': 'EXPERIMENTAL', 'label': 'Immuno-modulation Anakinra', 'interventionNames': ['Drug: Anakinra']}, {'type': 'EXPERIMENTAL', 'label': 'Cortico-steroids : Hydrocortisone', 'interventionNames': ['Drug: Hydrocortisone']}, {'type': 'EXPERIMENTAL', 'label': 'Cortico-steroids :Hydrocortisone and fludrocotisone', 'interventionNames': ['Drug: Hydrocortisone and fludrocortisone']}, {'type': 'EXPERIMENTAL', 'label': 'Coagulation : Heparin', 'interventionNames': ['Drug: Heparin']}, {'type': 'EXPERIMENTAL', 'label': 'Coagulation : Low molecular weight heparin', 'interventionNames': ['Drug: Low molecular weight heparin']}, {'type': 'EXPERIMENTAL', 'label': 'Coagulation : Recombinant humanThrombomodulin( rhTM)', 'interventionNames': ['Drug: Recombinant humanThrombomodulin( rhTM)']}, {'type': 'EXPERIMENTAL', 'label': 'Coagulation : Sivelestat', 'interventionNames': ['Drug: Sivelestat']}, {'type': 'EXPERIMENTAL', 'label': 'Coagulation : Fresh Frozen Plasma', 'interventionNames': ['Biological: Fresh frozen plasma']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Control', 'interventionNames': ['Other: Usual care']}], 'interventions': [{'name': 'Tocilizumab', 'type': 'DRUG', 'description': '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)', 'armGroupLabels': ['Immuno-modulation : Tocilizumab']}, {'name': 'Baricitinib', 'type': 'DRUG', 'description': '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)', 'armGroupLabels': ['Immuno-modulation Baricitinib']}, {'name': 'Anakinra', 'type': 'DRUG', 'description': '100 mg subcutaneously once daily for 10 days (or hospital discharge pending which will occur first) (same for adults and children)', 'armGroupLabels': ['Immuno-modulation Anakinra']}, {'name': 'Hydrocortisone', 'type': 'DRUG', 'description': '50mg (in children: 1-2 mg/kg) IV Q6 for 7 days', 'armGroupLabels': ['Cortico-steroids : Hydrocortisone']}, {'name': 'Hydrocortisone and fludrocortisone', 'type': 'DRUG', 'description': 'Hydrocortisone 50mg IV Q6 for 7 days + Fludrocortisone 50mg orally or via gastric tube once a day for 7 days.', 'armGroupLabels': ['Cortico-steroids :Hydrocortisone and fludrocotisone']}, {'name': 'Heparin', 'type': 'DRUG', 'description': '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).', 'armGroupLabels': ['Coagulation : Heparin']}, {'name': 'Low molecular weight heparin', 'type': 'DRUG', 'description': '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).', 'armGroupLabels': ['Coagulation : Low molecular weight heparin']}, {'name': 'Recombinant humanThrombomodulin( rhTM)', 'type': 'DRUG', 'description': 'Recombinant human thrombomodulin (rhTM) 0.06 mg/kg/j IV, for 7 days (or ICU discharge, pending which will occur first).', 'armGroupLabels': ['Coagulation : Recombinant humanThrombomodulin( rhTM)']}, {'name': 'Sivelestat', 'type': 'DRUG', 'description': '0.2 mg/kg/h for 7 days (or ICU discharge, pending which will occur first)', 'armGroupLabels': ['Coagulation : Sivelestat']}, {'name': 'Fresh frozen plasma', 'type': 'BIOLOGICAL', 'description': '12 ml/kg/day as long as INR remains \\>1.4', 'armGroupLabels': ['Coagulation : Fresh Frozen Plasma']}, {'name': 'Usual care', 'type': 'OTHER', 'description': 'Usual care', 'armGroupLabels': ['Control']}]}, 'contactsLocationsModule': {'centralContacts': [{'name': 'Djillali Annane, Pr', 'role': 'CONTACT', 'email': 'djillali.annane@aphp.fr', 'phone': '+33147107787'}, {'name': 'Jérôme Lambert', 'role': 'CONTACT', 'email': 'jerome.lambert@u-paris.fr', 'phone': '+33142499742'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Assistance Publique - Hôpitaux de Paris', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}