Ignite Creation Date:
2025-12-25 @ 2:32 AM
Ignite Modification Date:
2025-12-26 @ 1:08 AM
Study NCT ID:
NCT04285034
Status:
COMPLETED
Last Update Posted:
2021-10-13
First Post:
2020-02-18
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Cardiovascular Function and Ribavirin PK/PD in Lassa Fever in Lassa Fever
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D007835', 'term': 'Lassa Fever'}], 'ancestors': [{'id': 'D001117', 'term': 'Arenaviridae Infections'}, {'id': 'D012327', 'term': 'RNA Virus Infections'}, {'id': 'D014777', 'term': 'Virus Diseases'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D006482', 'term': 'Hemorrhagic Fevers, Viral'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITHOUT_DNA', 'description': 'PAXGene (RNA) DBS and FTA cards'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 158}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2019-11-26', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-10', 'completionDateStruct': {'date': '2021-07-15', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2021-10-12', 'studyFirstSubmitDate': '2020-02-18', 'studyFirstSubmitQcDate': '2020-02-25', 'lastUpdatePostDateStruct': {'date': '2021-10-13', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-02-26', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2021-07-15', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Cardiovascular Explanatory', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'To identify the frequency of vascular leak'}, {'measure': 'Cardiovascular Explanatory', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'To identify the frequency of cardiac function'}, {'measure': 'Cardiovascular Explanatory', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'To identify the frequency of total peripheral resistance'}, {'measure': 'Cardiovascular Explanatory', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'To identify the frequency of total body water'}, {'measure': 'Cardiovascular Explanatory', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'To identify the frequency of Reactive hyperaemic index'}, {'measure': 'Ribavirin Pharmacokinetics Explanatory', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'Age'}, {'measure': 'Ribavirin Pharmacokinetics Explanatory', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'Gender'}, {'measure': 'Ribavirin Pharmacokinetics Explanatory', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'Calculation of eGFR'}, {'measure': 'Ribavirin Pharmacokinetics Explanatory', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'Calculation of Total body water'}, {'measure': 'Ribavirin Pharmacokinetics Explanatory', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'ITPA, SLC28 gene polymorphisms'}, {'measure': 'Ribavirin Pharmacodynamics Explanatory', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'Calculation of AUC \\[AUC∞ and AUCLAST\\]'}, {'measure': 'Ribavirin Pharmacodynamics Explanatory', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'Calculation of CMAX'}, {'measure': 'Ribavirin Pharmacodynamics Explanatory', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'Calculation of CMIN'}, {'measure': 'Ribavirin Pharmacodynamics Explanatory', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'ITPA, IL28B and SLC28/29 gene polymorphisms'}], 'primaryOutcomes': [{'measure': 'Cardiovascular', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'Mean Arterial Pressure is less than 65mmHg or Systolic Blood Pressure is less than 90mmgHg or pulse pressure \\< 20mmHg'}, {'measure': 'Ribavirin Pharmacokinetics', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'Proportion of patients with ribavirin CMIN above the IC90 at \\> 80% of measured CMIN during therapy'}, {'measure': 'Ribavirin Pharmacodynamics', 'timeFrame': '5 days', 'description': 'Change in Lassa virus Viral Load from baseline to day 5'}], 'secondaryOutcomes': [{'measure': 'Cardiovascular', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'To identify the frequency of shock'}, {'measure': 'Cardiovascular', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'To identify the frequency of persistent shock'}, {'measure': 'Cardiovascular', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'To identify the frequency of respiratory distress'}, {'measure': 'Cardiovascular', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'To identify the frequency of shock and respiratory distress'}, {'measure': 'Cardiovascular', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'To identify the frequency of Death'}, {'measure': 'Ribavirin Pharmacokinetics', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'Proportion of patients with ribavirin CMIN above the IC50 at all measured CMIN during therapy'}, {'measure': 'Ribavirin Pharmacokinetics', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'Duration of time that ribavirin levels are above the IC90 and IC50'}, {'measure': 'Ribavirin Pharmacokinetics', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'Calculation of AUC \\[AUC∞ and AUCLAST\\] (ribavirin, ribavirin metabolites)'}, {'measure': 'Ribavirin Pharmacokinetics', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'Calculation of CMAX (ribavirin, ribavirin metabolites)'}, {'measure': 'Ribavirin Pharmacokinetics', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'Calculation of CMIN (ribavirin, ribavirin metabolites)'}, {'measure': 'Ribavirin Pharmacokinetics', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'Calculation of T1/2 (ribavirin, ribavirin metabolites)'}, {'measure': 'Ribavirin Pharmacokinetics', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'Volume of distribution (ribavirin, ribavirin metabolites)'}, {'measure': 'Ribavirin Pharmacokinetics', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'Calculation of Clearance (ribavirin, ribavirin metabolites)'}, {'measure': 'Ribavirin Pharmacodynamics', 'timeFrame': '10 days', 'description': 'Change in Lassa virus Viral Load from baseline to day 3 and day 10'}, {'measure': 'Ribavirin Pharmacodynamics', 'timeFrame': '10 days', 'description': 'Change in AST, ALT concentrations from baseline to day 3, 5, 10'}, {'measure': 'Ribavirin Pharmacodynamics', 'timeFrame': '10 days', 'description': 'Change in eGFR from baseline to day 3, 5, 10'}, {'measure': 'Ribavirin Pharmacodynamics', 'timeFrame': '10 days', 'description': 'Change in Haemoglobin from baseline to day 5, 10'}, {'measure': 'Ribavirin Pharmacodynamics', 'timeFrame': '5 days', 'description': 'Change in ISG expression from baseline to day 3, 5'}, {'measure': 'Ribavirin Pharmacodynamics', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'Time to negative blood RT-PCR for Lassa virus'}, {'measure': 'Ribavirin Pharmacodynamics', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'Requirement for blood transfusion during hospitalisation'}, {'measure': 'Ribavirin Pharmacodynamics', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'Reaching KDIGO stage 3 during hospitalisation'}, {'measure': 'Ribavirin Pharmacodynamics', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'Requirement for dialysis during hospitalisation'}, {'measure': 'Ribavirin Pharmacodynamics', 'timeFrame': 'through study completion, an average of 2 weeks', 'description': 'Duration of hospitalisation'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False}, 'conditionsModule': {'conditions': ['Lassa Fever']}, 'descriptionModule': {'briefSummary': "Arenaviruses are included in the World Health Organisation R\\&D Blueprint list of high priority pathogens, since this virus group includes several epidemic-prone highly pathogenic viruses for which there are inadequate diagnostic, therapeutic, and preventative interventions. Junin, Machupo, Guanarito, Sabia, Lujo, and Lassa virus can all cause a viral haemorrhagic fever with high case fatality in hospitalised cases. Lassa fever is the most common severe arenavirus disease and is endemic across many low and middle income countries in West Africa, with an estimated 37.7 million people in 14 countries living in areas at risk of Lassa virus. Despite the discovery of Lassa virus in 1972 and an estimated 300,000 cases and 5000-10,000 deaths annually, there remain gaps in our understanding of the natural history of disease and in the availability of evidence based interventions.\n\nThe protocol has two components. Sites may implement one or both components.\n\n1. Cardiovascular function in Lassa fever: Lassa fever in humans is often described in the literature as being characterized by vascular leak and shock in the terminal phase, this being the main pathway to death. Whilst animal data supports this, there are very limited data in humans. One of the main aims of this study therefore is to characterize cardiovascular function in patients with Lassa fever, with the ultimate goal of informing future trials of supportive or therapeutic strategies to improve vascular leak.\n2. Ribavirin pharmacokinetics and pharmacodynamics: The recommended treatment for Lassa is ribavirin, but its efficacy has not been established in randomized controlled trials and its mechanism of action is not fully understood. There are very limited PK data on ribavirin in patients with Lassa fever and the optimal dose of ribavirin for an RCT has not been established. Furthermore, there are various hypothesized mechanisms of action of ribavirin, none of which have been investigated in humans with Lassa fever. Therefore, further aims of this study are to characterize the PK of ribavirin and ribavirin metabolites (RMP, RDP, RTP) in Lassa fever patients and to identify potential mechanisms of action ribavirin in Lassa fever. Understanding Ribavirin's mechanism of action in Lassa fever is important for the optimal design of a future RCT.", 'detailedDescription': 'Summary of cardiovascular function study Lassa fever carries a treated mortality in hospitalized patients of up to 30%. Lassa fever is often described as being characterized by vascular leak and shock in the terminal phase, but, whilst animal data supports this, there are limited data in humans. A further aim of this study therefore is to characterize cardiovascular function in patients with Lassa fever, with the ultimate goal of informing future trials of supportive or therapeutic strategies.\n\nSummary of ribavirin pharmacokinetics and pharmacodynamics sub-study Lassa fever carries a treated mortality in hospitalized patients of up to 30% in Nigeria. Ribavirin is the current standard of care. However, the efficacy of ribavirin has not been established in RCTs. There is very limited PK data on ribavirin in patients with Lassa fever and the optimal dose of ribavirin for an RCT is unknown. The aim of this study is to characterize the PK of ribavirin in Lassa fever, and identify any associations between ribavirin PK parameters and viral load and markers of inflammatory status.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'minimumAge': '10 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Patients admitted to Lassa fever treatment centres with a diagnosis of suspected or RT-PCR confirmed Lassa fever.', 'healthyVolunteers': False, 'eligibilityCriteria': 'Cardiovascular Study:\n\nInclusion Criteria:\n\n* Suspected or RT-PCR confirmed Lassa fever diagnosis\n* Aged 10 years or above\n\nExclusion Criteria:\n\n• None\n\nRibavirin PK/PD study\n\nInclusion Criteria:\n\n* Suspected or RT-PCR confirmed Lassa fever diagnosis\n* Patient will receive ribavirin therapy\n* Aged 10 years or above\n\nExclusion Criteria:\n\n• None'}, 'identificationModule': {'nctId': 'NCT04285034', 'briefTitle': 'Cardiovascular Function and Ribavirin PK/PD in Lassa Fever in Lassa Fever', 'organization': {'class': 'OTHER', 'fullName': 'University of Oxford'}, 'officialTitle': 'Cardiovascular Function and Ribavirin Pharmacokinetics and Pharmacodynamics in Lassa Fever Patients in Nigeria: a Prospective Observational Cohort Study', 'orgStudyIdInfo': {'id': '04-19'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Ribavirin only', 'description': 'Patients will receive ribavirin in accordance with Nigerian treatment guidelines. Patients will either receive the McCormick regimen or the Irrua regimen.\n\nPK blood tests will be done on Day 1,2,5,6,10,11,12,13, discharge; Paxgene RNA blood test on day 1, 3, 5, discharge Haematocrit finger prick test on day 1,2, 5, 6, 10, discharge'}, {'label': 'Cardiocascular study only', 'description': 'Cardiac tests (NICAS (daily), ECG (Day 1, 5, 10, discharge), Echocardiogram (Day 1, 5, discharge), Ultrasound (Day 1, 3, 5, 7, 10), Endopat (Day 1 and discharge)) will be done throughout; Haematocrit finger prick test daily PAXgene RNA blood test on day 1, 5, discharge'}]}, 'contactsLocationsModule': {'locations': [{'zip': 'PMB 1053', 'city': 'Owo', 'state': 'Ondo State', 'country': 'Nigeria', 'facility': 'Owo Federal Medical Centre', 'geoPoint': {'lat': 7.1962, 'lon': 5.58681}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Oxford', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}