Ignite Creation Date:
2026-03-26 @ 3:20 PM
Ignite Modification Date:
2026-03-31 @ 3:51 AM
Study NCT ID:
NCT07419802
Status:
RECRUITING
Last Update Posted:
2026-02-19
First Post:
2026-01-28
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
OxiCLEAR (Oxiris Cytokines and Endotoxin Adsorption Rate) Study
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D018805', 'term': 'Sepsis'}, {'id': 'D012772', 'term': 'Shock, Septic'}, {'id': 'D019446', 'term': 'Endotoxemia'}], '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'}, {'id': 'D012769', 'term': 'Shock'}, {'id': 'D016470', 'term': 'Bacteremia'}, {'id': 'D014115', 'term': 'Toxemia'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000079664', 'term': 'Continuous Renal Replacement Therapy'}], 'ancestors': [{'id': 'D017582', 'term': 'Renal Replacement Therapy'}, {'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D005112', 'term': 'Extracorporeal Circulation'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2026-01-23', 'size': 306955, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2026-02-16T04:01', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Blood and effluent samples will be collected from each patient before Oxiris® CVVH initiation (T0) and at 1h, 3h, 6h, 12h, and 24h pre- and post-filter to measure endotoxin and inflammatory mediator concentrations, assess membrane time to saturation and clearance rates, and evaluate systemic response. Blood samples will also be analyzed for complete blood count (hemoglobin, leukocytes, platelets), coagulation markers, inflammatory markers (PCT, CRP, IL-6), and kidney and liver function biomarkers. Samples will be retained for research purposes only, following standard preservation protocols, with anonymization to protect patient confidentiality.'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 29}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2026-03-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-02', 'completionDateStruct': {'date': '2027-09-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-02-16', 'studyFirstSubmitDate': '2026-01-28', 'studyFirstSubmitQcDate': '2026-02-16', 'lastUpdatePostDateStruct': {'date': '2026-02-19', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-02-19', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-09-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Endotoxin adsorptive capacity of the Oxiris® membrane', 'timeFrame': 'Baseline, and 1, 3, 6, 12 and 24 hours after initiation of CVVH with Oxiris®.', 'description': 'Endotoxin adsorption rate calculated from the difference between inlet (C\\_in) and outlet (C\\_out) endotoxin concentrations multiplied by plasma flow (Qp) and normalized to membrane surface area (U/cm²/min), reflecting true membrane adsorption.'}, {'measure': 'Cytokine adsorptive capacity and cytokine clearance over time', 'timeFrame': 'Baseline and 1, 3, 6, 12 and 24 hours after initiation of CVVH with Oxiris®.', 'description': 'Cytokine removal quantified by (i) total plasma clearance (from C\\_in and C\\_out), (ii) convective clearance (from effluent concentration × effluent flow), and (iii) adsorptive clearance (plasma clearance minus convective clearance), normalized to membrane surface area.'}], 'secondaryOutcomes': [{'measure': 'Hemodynamic changes associated with membrane adsorption performance', 'timeFrame': 'Baseline and 24 hours after initiation of CVVH with Oxiris®', 'description': 'Changes in vasopressor requirements in relation to Oxiris® membrane adsorption performance during 24 hours of treatment'}, {'measure': 'Lactate changes associated with membrane adsorption performance', 'timeFrame': 'Baseline and 24 hours after initiation of CVVH with Oxiris®', 'description': 'Changes in serum lactate in relation to Oxiris® adsorption performance during 24 hours of treatment'}, {'measure': 'Changes in Sequential Organ Failure Assessment score in relation to Oxiris® adsorption performance at 24 hours', 'timeFrame': 'Baseline and 24 hours after initiation of CVVH with Oxiris®', 'description': 'Changes in Sequential Organ Failure Assessment score in relation to Oxiris® adsorption performance at 24 hours. With a minimum score of 0 points and a maximum of 24 points, higher scores indicate worse outcomes.'}, {'measure': 'Inflammatory marker (C-reactive protein) response associated with membrane adsorption performance', 'timeFrame': 'Baseline and 24 hours after initiation of CVVH with Oxiris®', 'description': 'Changes in C-reactive protein concentration in relation to Oxiris® adsorption performance during 24 hours of treatment'}, {'measure': 'Inflammatory markers (Procalcitonin) response associated with membrane adsorption performance', 'timeFrame': 'Baseline and 24 hours after initiation of CVVH with Oxiris®', 'description': 'Changes in serum procalcitonin in relation to Oxiris® adsorption performance during 24 hours of treatment'}, {'measure': 'Inflammatory mediator (Interleukin-6) response associated with membrane adsorption performance', 'timeFrame': 'Baseline and 24 hours after initiation of CVVH with Oxiris®', 'description': 'Changes in Interleukin-6 concentration in relation to Oxiris® adsorption performance during 24 hours of treatment'}, {'measure': '28-day mortality', 'timeFrame': 'From initiation of CVVH to Day 28.', 'description': 'All-cause 28-day mortality, analyzed in relation to Oxiris® membrane adsorption performance and saturation dynamics.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Oxiris', 'blood purification', 'hemoadsorption', 'septic shock', 'saturation phenomena', 'Continuous renal replacement therapy (CRRT)', 'AN69-polyethylenimine membrane', 'Endotoxin adsorption', 'Cytokine adsorption', 'Membrane saturation', 'Mass balance', 'Inlet-outlet concentration gradient', 'Membrane fouling', 'Precision blood purification', 'Endotoxemia'], 'conditions': ['Sepsis', 'Septic Shock', 'Blood Purification', 'Hemoadsorption']}, 'descriptionModule': {'briefSummary': 'This study examines how well the Oxiris® hemofilter works over time in adults with septic shock who require continuous kidney support in the intensive care unit (ICU).\n\nSeptic shock is a severe form of infection that leads to organ failure, including acute kidney injury. Many people with septic shock require continuous renal replacement therapy (CRRT), a form of dialysis that runs continuously to support the kidneys. The Oxiris® hemofilter is a special type of CRRT filter designed not only to replace kidney function but also to remove harmful substances from the blood, including endotoxins from bacteria and inflammatory proteins (cytokines).\n\nAlthough Oxiris® is widely used, it is not known how long the filter continues to remove these substances effectively. Over time, the membrane of the filter may become filled with endotoxins and cytokines, which could reduce its ability to clean the blood. This study aims to determine whether and when this loss of adsorption occurs during a standard twenty-four-hour treatment period.\n\nAdults with septic shock who receive Oxiris® as part of routine ICU care will take part in this observational study. No experimental treatment will be given. Blood samples will be taken before and after the filter, and fluid leaving the filter will be collected, to measure how endotoxins and cytokines are removed over time.\n\nThe study will also assess how changes in filter performance relate to clinical markers such as blood pressure support, blood lactate levels, organ function scores, kidney recovery, and twenty-eight-day survival.\n\nThe results will help define the optimal timing for Oxiris® filter replacement and support more effective use of blood purification therapy in patients with septic shock.', 'detailedDescription': "This is a prospective, single-center, observational study designed to characterize the adsorption capacity and saturation dynamics of the AN69-polyethylenimine membrane (Oxiris® hemofilter) during continuous veno-venous hemofiltration (CVVH) in adult patients with septic shock.\n\nThe Oxiris® hemofilter is approved for continuous renal replacement therapy (CRRT) for up to 72 hours in patients with sepsis-associated acute kidney injury; however, in routine clinical practice the filter is commonly replaced after 12-24 hours because of concerns regarding declining adsorption efficiency. The biological basis for this practice remains insufficiently defined. This study aims to provide in vivo quantitative evidence on how endotoxin and cytokine adsorption by the Oxiris® membrane changes over time and whether cytokine clearance persists through convective transport when adsorption capacity is reduced.\n\nThe primary objective is to quantify the adsorption capacity of the AN69-polyethylenimine membrane for endotoxins and inflammatory mediators over a continuous 24-hour CVVH treatment period. Secondary objectives are to determine whether membrane adsorption efficiency declines over time in a manner consistent with saturation, to quantify cytokine clearance via convective transport into the effluent, and to evaluate whether reduced membrane adsorption is associated with clinical course and outcomes in septic shock.\n\nAdult patients (≥18 years) with septic shock admitted to the intensive care unit of Pauls Stradiņš Clinical University Hospital will be enrolled. All patients will receive CVVH with the Oxiris® hemofilter as part of standard-of-care management. Eligibility requires fulfillment of Sepsis-3 septic shock criteria, a Dynamic Scoring System (DSS) score of 6-8, and treatment with CVVH for at least 24 hours. Baseline endotoxin concentration will be used to define the primary analytical cohort.\n\nAll patients will be treated using CVVH with the PrisMax platform and Oxiris® membrane under standardized conditions to ensure comparability of adsorption kinetics: blood flow 100-150 mL/min, filtration dose 25-30 mL/kg/h, regional citrate anticoagulation, replacement fluid 1000-1500 mL/h with 50% pre- and post-dilution, and net ultrafiltration of 0 mL/h.\n\nBlood and effluent samples will be collected at baseline (T0) and at 1, 3, 6, 12, and 24 hours after initiation of CVVH. At each time point, inlet (arterial line) plasma, outlet (venous line) plasma, and effluent will be obtained. A total of 17 samples per patient will be collected. Samples will be centrifuged immediately and stored at -80 °C until analysis.\n\nEndotoxin concentrations will be measured using a competitive ELISA assay with high analytical sensitivity. Inflammatory mediators, including IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, MCP-1, VEGF, and EGF, will be quantified using a multiplex biochip analyzer.\n\nFor endotoxins, removal occurs exclusively via adsorption. Adsorption rate will be calculated from the inlet-outlet concentration difference multiplied by plasma flow rate and normalized to membrane surface area (U/cm²/min). For cytokines, total plasma clearance will be calculated from inlet and outlet concentrations, convective clearance from effluent concentration multiplied by effluent flow rate, and adsorptive clearance as the difference between plasma and effluent clearance. This approach allows separation of cytokine removal by adsorption and convection and enables determination of whether cytokine clearance persists when membrane adsorption capacity declines.\n\nClinical data will include demographics, comorbidities, SOFA and Dynamic scores, source of infection, antimicrobial therapy, hemodynamic variables, vasopressor dose, lactate, CRP, procalcitonin, renal and liver function, and CRRT technical parameters including blood flow, transmembrane pressure, and filter pressure gradients. Clinical outcomes include 28-day mortality, renal recovery, vasopressor-free days, and ICU length of stay.\n\nThe primary endpoint is the adsorption rate of endotoxins and inflammatory mediators. The primary analysis evaluates the relationship between inlet endotoxin concentration and adsorption rate across repeated time points. Pearson correlation coefficients will be calculated and transformed using Fisher's Z transformation to obtain a pooled estimate of correlation over time. A decline in this relationship will be interpreted as evidence of reduced membrane adsorption capacity consistent with saturation. Time-dependent changes in adsorption will also be analyzed using linear mixed-effects models with patient as a random effect and time, inlet concentration, transmembrane pressure, and filter age as fixed effects.\n\nFor cytokines, the relative contribution of convective versus adsorptive clearance will be modeled over time to determine whether convective transport remains effective when adsorption declines. Associations between early membrane saturation and clinical outcomes (e.g., lactate reduction, vasopressor requirements, SOFA score, renal recovery, and 28-day mortality) will be explored using mixed-effects regression, logistic regression, and Cox proportional hazards models as appropriate.\n\nTwenty-nine patients provide sufficient power to detect clinically meaningful changes in adsorption dynamics based on preliminary correlation estimates. Continuous variables will be summarized as mean ± standard deviation or median with interquartile range, and categorical variables as counts and percentages. Missing data will be handled using complete-case analysis, with multiple imputation applied if missingness exceeds 5%.\n\nAll data will be stored in a secure electronic database with predefined range and consistency checks. Laboratory values will be verified against certified laboratory records and clinical data against ICU medical records. Standard operating procedures govern patient enrollment, sample handling, laboratory analysis, data management, and statistical evaluation."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'The study population will include adult patients (≥18 years of age) of any gender who are diagnosed with septic shock and admitted to the intensive care unit (ICU). All enrolled patients must receive continuous veno-venous hemofiltration (CVVH) with a high-adsorptive AN69-polyethyleneimine membrane (Oxiris®) for a minimum duration of 24 hours as part of their clinical management.', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria (should meet all the criteria mentioned below):\n\n* Septic shock patient with a Dynamic scoring system of 6-8 points /Septic shock definition based on Sepsis-3: a vasopressor requirement to maintain a mean arterial pressure of 65 mmHg or greater and serum lactate greater than 2mmol/L despite optimal (30ml/kg body weight) bolus fluid resuscitation/\n* CVVH with AN69-polyethylenimine (Oxiris) membrane for at least 24 hours\n* Age \\>18 years\n\nExclusion Criteria:\n\n* Age \\< 18 years\n* Pregnancy\n* Known contraindications to citrate anticoagulation\n* High likelihood of death within 24 hours due to irreversible comorbidities (e.g., end-stage cardiac, pulmonary, or hepatic disease; hepatorenal syndrome; advanced uncontrolled malignancy)\n* Simultaneous treatment with another adsorption device during the study period'}, 'identificationModule': {'nctId': 'NCT07419802', 'acronym': 'OxiCLEAR', 'briefTitle': 'OxiCLEAR (Oxiris Cytokines and Endotoxin Adsorption Rate) Study', 'organization': {'class': 'OTHER', 'fullName': 'Pauls Stradins Clinical University Hospital'}, 'officialTitle': "Endotoxin and Cytokine Adsorption Properties of the Oxiris Hemofilter in Septic Shock: Evaluation of Saturation Phenomena and Inflammatory Mediators' Clearance Capacity", 'orgStudyIdInfo': {'id': '2-PĒK-4/429/2022'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Oxiris CVVH Septic Shock Cohort', 'description': 'Adult patients with septic shock admitted to the intensive care unit and treated with continuous veno-venous hemofiltration (CVVH) using the Oxiris® hemofilter as part of standard-of-care therapy. All participants receive the same CRRT modality; no comparator or control group is included. The cohort is used to evaluate time-dependent endotoxin and cytokine removal, membrane adsorption performance, and cytokine convective clearance during a 24-hour Oxiris® treatment period.', 'interventionNames': ['Device: AN69-polyethylenimine hemofilter (Oxiris®) used for continuous veno-venous hemofiltration (CVVH)']}], 'interventions': [{'name': 'AN69-polyethylenimine hemofilter (Oxiris®) used for continuous veno-venous hemofiltration (CVVH)', 'type': 'DEVICE', 'description': 'Continuous veno-venous hemofiltration (CVVH) performed using the AN69-polyethylenimine (Oxiris®) hemofilter as part of standard-of-care treatment in adult patients with septic shock. The Oxiris® membrane is a high-adsorptive, polyethyleneimine-coated AN69 filter designed for simultaneous renal replacement therapy and removal of circulating endotoxins and inflammatory mediators. CVVH is delivered using standardized clinical settings, including blood flow 100-150 mL/min, filtration dose 25-30 mL/kg/h, regional citrate anticoagulation, and a 24-hour treatment period with serial blood and effluent sampling to assess membrane adsorption and convective clearance.', 'armGroupLabels': ['Oxiris CVVH Septic Shock Cohort']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'LV1002', 'city': 'Riga', 'status': 'RECRUITING', 'country': 'Latvia', 'contacts': [{'name': 'Darja Smirnova, MD', 'role': 'CONTACT', 'email': 'darja.smirnova@rsu.lv', 'phone': '+37126359852'}], 'facility': 'Pauls Stradiņš Clinical University Hospital, Department of Anesthesiology and Reanimatology', 'geoPoint': {'lat': 56.946, 'lon': 24.10589}}], 'centralContacts': [{'name': 'Darja Smirnova, MD', 'role': 'CONTACT', 'email': 'darja.smirnova@rsu.lv', 'phone': '+37126359852'}, {'name': 'Olegs Sabelnikovs, Prof', 'role': 'CONTACT', 'email': 'olegs.sabelnikovs@stradini.lv', 'phone': '+37129561827'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Pauls Stradins Clinical University Hospital', 'class': 'OTHER'}, 'collaborators': [{'name': 'Vantive Health LLC', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}