Nctid:
NCT06222723
Payload:
{"hasResults"=>false, "derivedSection"=>{"miscInfoModule"=>{"versionHolder"=>"2024-10-04"}, "conditionBrowseModule"=>{"meshes"=>[{"id"=>"D000007835", "term"=>"Lassa Fever"}, {"id"=>"D000005334", "term"=>"Fever"}], "ancestors"=>[{"id"=>"D000001832", "term"=>"Body Temperature Changes"}, {"id"=>"D000001117", "term"=>"Arenaviridae Infections"}, {"id"=>"D000012327", "term"=>"RNA Virus Infections"}, {"id"=>"D000014777", "term"=>"Virus Diseases"}, {"id"=>"D000007239", "term"=>"Infections"}, {"id"=>"D000006482", "term"=>"Hemorrhagic Fevers, Viral"}], "browseLeaves"=>[{"id"=>"M8464", "name"=>"Fever", "asFound"=>"Fever", "relevance"=>"HIGH"}, {"id"=>"M2454", "name"=>"Hyperthermia", "relevance"=>"LOW"}, {"id"=>"M10850", "name"=>"Lassa Fever", "asFound"=>"Lassa Fever", "relevance"=>"HIGH"}, {"id"=>"M5111", "name"=>"Body Temperature Changes", "relevance"=>"LOW"}, {"id"=>"M10283", "name"=>"Infections", "relevance"=>"LOW"}, {"id"=>"M6368", "name"=>"Communicable Diseases", "relevance"=>"LOW"}, {"id"=>"M17522", "name"=>"Virus Diseases", "relevance"=>"LOW"}, {"id"=>"M15149", "name"=>"RNA Virus Infections", "relevance"=>"LOW"}, {"id"=>"M9568", "name"=>"Hemorrhagic Fevers, Viral", "relevance"=>"LOW"}, {"id"=>"T5864", "name"=>"Viral Hemorrhagic Fever", "relevance"=>"LOW"}], "browseBranches"=>[{"name"=>"Symptoms and General Pathology", "abbrev"=>"BC23"}, {"name"=>"All Conditions", "abbrev"=>"All"}, {"name"=>"Wounds and Injuries", "abbrev"=>"BC26"}, {"name"=>"Infections", "abbrev"=>"BC01"}, {"name"=>"Rare Diseases", "abbrev"=>"Rare"}]}, "interventionBrowseModule"=>{"meshes"=>[{"id"=>"D000012254", "term"=>"Ribavirin"}, {"id"=>"D000003907", "term"=>"Dexamethasone"}], "ancestors"=>[{"id"=>"D000000893", "term"=>"Anti-Inflammatory Agents"}, {"id"=>"D000000932", "term"=>"Antiemetics"}, {"id"=>"D000001337", "term"=>"Autonomic Agents"}, {"id"=>"D000018373", "term"=>"Peripheral Nervous System Agents"}, {"id"=>"D000045505", "term"=>"Physiological Effects of Drugs"}, {"id"=>"D000005765", "term"=>"Gastrointestinal Agents"}, {"id"=>"D000005938", "term"=>"Glucocorticoids"}, {"id"=>"D000006728", "term"=>"Hormones"}, {"id"=>"D000006730", "term"=>"Hormones, Hormone Substitutes, and Hormone Antagonists"}, {"id"=>"D000018931", "term"=>"Antineoplastic Agents, Hormonal"}, {"id"=>"D000000970", "term"=>"Antineoplastic Agents"}, {"id"=>"D000000963", "term"=>"Antimetabolites"}, {"id"=>"D000045504", "term"=>"Molecular Mechanisms of Pharmacological Action"}, {"id"=>"D000000998", "term"=>"Antiviral Agents"}, {"id"=>"D000000890", "term"=>"Anti-Infective Agents"}], "browseLeaves"=>[{"id"=>"M7102", "name"=>"Dexamethasone", "asFound"=>"High", "relevance"=>"HIGH"}, {"id"=>"M235549", "name"=>"Dexamethasone acetate", "relevance"=>"LOW"}, {"id"=>"M15083", "name"=>"Ribavirin", "asFound"=>"Light", "relevance"=>"HIGH"}, {"id"=>"M4314", "name"=>"Antiviral Agents", "relevance"=>"LOW"}, {"id"=>"M4217", "name"=>"Anti-Inflammatory Agents", "relevance"=>"LOW"}, {"id"=>"M4251", "name"=>"Antiemetics", "relevance"=>"LOW"}, {"id"=>"M8881", "name"=>"Gastrointestinal Agents", "relevance"=>"LOW"}, {"id"=>"M9047", "name"=>"Glucocorticoids", "relevance"=>"LOW"}, {"id"=>"M9789", "name"=>"Hormones", "relevance"=>"LOW"}, {"id"=>"M9788", "name"=>"Hormone Antagonists", "relevance"=>"LOW"}, {"id"=>"M20966", "name"=>"Antineoplastic Agents, Hormonal", "relevance"=>"LOW"}, {"id"=>"M4281", "name"=>"Antimetabolites", "relevance"=>"LOW"}, {"id"=>"M4214", "name"=>"Anti-Infective Agents", "relevance"=>"LOW"}], "browseBranches"=>[{"name"=>"Anti-Inflammatory Agents", "abbrev"=>"Infl"}, {"name"=>"Antineoplastic Agents", "abbrev"=>"ANeo"}, {"name"=>"Antiemetics", "abbrev"=>"AnEm"}, {"name"=>"Gastrointestinal Agents", "abbrev"=>"Gast"}, {"name"=>"All Drugs and Chemicals", "abbrev"=>"All"}, {"name"=>"Anti-Infective Agents", "abbrev"=>"Infe"}]}}, "protocolSection"=>{"designModule"=>{"phases"=>["PHASE2"], "studyType"=>"INTERVENTIONAL", "designInfo"=>{"allocation"=>"RANDOMIZED", "maskingInfo"=>{"masking"=>"NONE"}, "primaryPurpose"=>"TREATMENT", "interventionModel"=>"PARALLEL"}, "enrollmentInfo"=>{"type"=>"ESTIMATED", "count"=>42}}, "statusModule"=>{"overallStatus"=>"NOT_YET_RECRUITING", "startDateStruct"=>{"date"=>"2024-01", "type"=>"ESTIMATED"}, "expandedAccessInfo"=>{"hasExpandedAccess"=>false}, "statusVerifiedDate"=>"2023-12", "completionDateStruct"=>{"date"=>"2026-12", "type"=>"ESTIMATED"}, "lastUpdateSubmitDate"=>"2024-01-15", "studyFirstSubmitDate"=>"2023-09-29", "studyFirstSubmitQcDate"=>"2024-01-15", "lastUpdatePostDateStruct"=>{"date"=>"2024-01-25", "type"=>"ACTUAL"}, "studyFirstPostDateStruct"=>{"date"=>"2024-01-25", "type"=>"ACTUAL"}, "primaryCompletionDateStruct"=>{"date"=>"2026-12", "type"=>"ESTIMATED"}}, "outcomesModule"=>{"primaryOutcomes"=>[{"measure"=>"Proportion of treatment emergent adverse events and treatment emergent serious adverse events", "timeFrame"=>"Participants will be followed up until day 10 after enrollment.", "description"=>"Documentation of events"}], "secondaryOutcomes"=>[{"measure"=>"Unfavourable outcome", "timeFrame"=>"Participants will be followed up until day 10 after enrollment.", "description"=>"The outcome is measured by the proportion of participants reaching a composite endpoint.\n\nThe outcome is reached if there is a new onset of any of the following: acute kidney injury (KDIGO 3), acute respiratory distress syndrome (SpO2/FiO2 ≤ 315), shock (mean blood pressure \\< 65 mmHg or systolic blood pressure \\< 90 mmHg ), encephalopathy (CVPU or seizure), death (yes/no);"}, {"measure"=>"Mean/median decline and area under the curve (AUC) of AST, ALT, CK, LDH and CRP", "timeFrame"=>"Participants will be followed up until day 10 after enrollment.", "description"=>"Blood analyses"}, {"measure"=>"Description of: proinflammatory plasma cytokine levels and lymphocyte phenotype under treatment", "timeFrame"=>"Participants will be followed up until day 10 after enrollment.", "description"=>"Assays such as the enzyme-linked immunosorbent assays (ELISA) and/or immunofluorescence assays will be used to retrospectively determine LASV IgM and IgG, as well as further IgG subclassification if needed, and to monitor the development of LASV specific antibodies in blood.\n\nLongitudinal development of inflammatory biomarkers such as IFNα, TNFα, IL-6, and IL-8 will be measured in plasma using bead-based multiplex assays. The phenotype of lymphocytes will be described using flow cytometry."}, {"measure"=>"Description of evolution of viral loads and infectious titers over time until day 10", "timeFrame"=>"Participants will be followed up until day 10 after enrollment.", "description"=>"Virus titers will be determined. Viral growth, isolation of LASV in cell culture, virus sequencing and unbiased metagenomic sequencing will be used on selected samples to study the longitudinal impact of drug treatment (ribavirin and dexamethasone) on LASV genomes."}, {"measure"=>"Evolution of selected virus gene sequences under treatment", "timeFrame"=>"Participants will be followed up until day 10 after enrollment.", "description"=>"Virus sequencing"}, {"measure"=>"Peak plasma concentration (Cmax)", "timeFrame"=>"Participants will be followed up until day 10 after enrollment.", "description"=>"Compartmental analysis"}, {"measure"=>"Time to peak plasma concentration (Tmax)", "timeFrame"=>"Participants will be followed up until day 10 after enrollment.", "description"=>"Compartmental analysis"}, {"measure"=>"Area under the plasma concentration versus time curve (AUC)", "timeFrame"=>"Participants will be followed up until day 10 after enrollment.", "description"=>"Compartmental analysis"}, {"measure"=>"Half life (T 1/2)", "timeFrame"=>"Participants will be followed up until day 10 after enrollment.", "description"=>"Compartmental analysis"}, {"measure"=>"Volume of distribution (Vd)", "timeFrame"=>"Participants will be followed up until day 10 after enrollment.", "description"=>"Compartmental analysis"}]}, "oversightModule"=>{"isFdaRegulatedDrug"=>false, "isFdaRegulatedDevice"=>false}, "conditionsModule"=>{"conditions"=>["Lassa Fever"]}, "descriptionModule"=>{"briefSummary"=>"Dexamethasone is a corticosteroid which can modulate inflammatory-mediated tissue damage associated with a wide range of infectious diseases. Dexamethasone is routinely used for treatment of tuberculous meningitis and for pneumococcal meningitis in adults. In Coronavirus Disease 2019 (COVID-19) dexamethasone is also effectively preventing immune mediated damage of the lungs. There is also indication that dexamethasone may be promising in severe LF.", "detailedDescription"=>"Lassa fever (LF) is a severe and often fatal systemic disease in humans. It is caused by the Lassa virus (LASV). Vaccines are not available yet and treatment options are limited to supportive care and ribavirin. Recent LF outbreaks in Nigeria showed an exceptionally high and increasing incidence of LF cases LF affects a large number of countries in West Africa. The pathophysiology of LF is not fully understood yet. It is hypothesized that the damage mediated by the host's defence is plays a key role in the pathophysiology of severe LF. Dexamethasone is considered to dampen the overactive immune response in a range of infectious diseases and thus preventing consecutive damage mediated by the host's immune system, while the antiinfective therapy is effectively treating the underlying pathogen. At the Irrua Specialist Teaching Hospital (ISTH) in Nigeria, one of the largest treatment centres for LF in West-Africa, dexamethasone has been successfully used in clinical practice to manage co-infections of LASV and Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2).\n\nTo evaluate Dexamethasone for the treatment of moderate to severe LF cases, a prospective open label randomized controlled phase II clinical trial will be conducted:\n\n1. Standard of care antiviral ribavirin therapy\n2. Standard of care antiviral ribavirin therapy + dexamethasone\n\nThe primary objective is to assess safety and tolerability of dexamethasone in moderate to severe LF when administered as adjunct treatment. Secondary objectives are to assess the effect of the study intervention on disease progression; to assess immunological and virological impact of dexamethasone therapy and the characterization of population pharmacokinetic characteristics for patients treated with adjunct dexamethasone therapy."}, "eligibilityModule"=>{"sex"=>"ALL", "stdAges"=>["ADULT", "OLDER_ADULT"], "minimumAge"=>"18 years", "healthyVolunteers"=>false, "eligibilityCriteria"=>"Inclusion Criteria:\n\n* Age ≥ 18 years\n* LF confirmed by RT-PCR (reverse-transcription polymerase chain reaction) with a cycle threshold (Ct) value \\< 30\n* Signs of significant health impairment as evidenced by any of the following:\n* Alert, confusion, voice, pain, unresponsive (ACVPU) other than A\n* Systolic blood pressure \\< 90 mmHg\n* Seizure(s), meningism, coma, focal neurological deficit\n* AST (GOT) \\>3xULN\n* ALT (GPT) \\> 3xULN\n* KDIGO 2 or more severe based on serum creatinine only\n* Active macroscopic bleeding\n* O2 saturation \\< 92\n\nExclusion Criteria:\n\n* Pregnancy (evidenced by positive urine pregnancy test in women of child-bearing potential)\n* Lactation following live birth\n* Known intolerance and contra-indications to ribavirin or dexamethasone\n* Patients who already received a corticosteroid within the preceding 7 days\n* Investigator's valuation that patient might be put to substantial risk by participating in this trial\n* Patients receiving end-of-life care as judged by the investigator"}, "identificationModule"=>{"nctId"=>"NCT06222723", "acronym"=>"LADEX", "briefTitle"=>"LAssa Fever Adjunct Treatment With DEXamethasone", "organization"=>{"class"=>"OTHER_GOV", "fullName"=>"Bernhard Nocht Institute for Tropical Medicine"}, "officialTitle"=>"Safety and Tolerability of Adjunct Dexamethasone in Addition to Standard of Care Antiviral Therapy Compared to Standard of Care Antiviral Therapy Alone for the Treatment of Moderate to Severe Lassa Fever", "orgStudyIdInfo"=>{"id"=>"1.0 (17 July 2023)"}, "secondaryIdInfos"=>[{"id"=>"20231908/486", "type"=>"OTHER", "domain"=>"ISTH EC, Nigeria"}, {"id"=>"2023-101164-BO-ff", "type"=>"OTHER", "domain"=>"EC Hamburg, Germany"}]}, "armsInterventionsModule"=>{"armGroups"=>[{"type"=>"ACTIVE_COMPARATOR", "label"=>"Standard of care", "description"=>"Standard of care antiviral ribavirin therapy", "interventionNames"=>["Drug: Ribavirin"]}, {"type"=>"EXPERIMENTAL", "label"=>"Standard of care + dexamethasone", "description"=>"Standard of care antiviral ribavirin therapy + dexamethasone", "interventionNames"=>["Drug: Dexamethasone", "Drug: Ribavirin"]}], "interventions"=>[{"name"=>"Dexamethasone", "type"=>"DRUG", "description"=>"Dexamethasone will be administered for 10 days. For the first 48 hours, dexamethasone will be given iv. After 48 hours, a switch to oral dexamethasone (same dosage) is permitted at the discretion of the study physician.", "armGroupLabels"=>["Standard of care + dexamethasone"]}, {"name"=>"Ribavirin", "type"=>"DRUG", "description"=>"Ribavirin treatment will be administered iv for 10 days, as recommended in the Nigeria Centre for Disease Control and Prevention National Guidelines for LF Case Management.", "armGroupLabels"=>["Standard of care", "Standard of care + dexamethasone"]}]}, "contactsLocationsModule"=>{"centralContacts"=>[{"name"=>"Mirjam Groger, Dr.", "role"=>"CONTACT", "email"=>"groger@bnitm.de", "phone"=>"+49 40 285380 480"}, {"name"=>"Stephan Günther, Prof.", "role"=>"CONTACT", "email"=>"guenther@bnitm.de", "phone"=>"+49 40 285380 547"}], "overallOfficials"=>[{"name"=>"Stephan Günther, Prof.", "role"=>"STUDY_DIRECTOR", "affiliation"=>"Bernhard Nocht Institute for Tropical Medicine"}]}, "ipdSharingStatementModule"=>{"ipdSharing"=>"NO", "description"=>"Case by case decision upon request"}, "sponsorCollaboratorsModule"=>{"leadSponsor"=>{"name"=>"Bernhard Nocht Institute for Tropical Medicine", "class"=>"OTHER_GOV"}, "responsibleParty"=>{"type"=>"SPONSOR"}}}}
