[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100657176":3},{"organization":4,"outcomesModule":7,"designInfo":67,"detailedDescription":79,"studyPopulation":70,"armGroups":80,"interventions":93,"overallOfficials":102,"centralContacts":106,"locations":112,"responsibleParty":362,"collaborators":70,"id":364,"slug":365,"hasResults":366,"nctId":367,"briefTitle":368,"officialTitle":368,"acronym":369,"eligibilityCriteria":370,"healthyVolunteers":366,"sex":371,"minAge":372,"maxAge":70,"enrollmentInfo":373,"targetDuration":70,"studyType":376,"phases":377,"briefSummary":379,"conditions":380,"keywords":382,"overallStatus":115,"whyStopped":70,"lastUpdateSubmitDate":389,"lastUpdatePostDateStruct":390,"startDateStruct":393,"completionDateStruct":395,"leadSponsor":397,"locationsCount":398},{"fullName":5,"class":6},"Hellenic Institute for the Study of Sepsis","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":60},[9],{"measure":10,"description":11,"timeFrame":12},"Incidence of new infection","The incidence of new infection within 28 days following randomization, comparing intravenous or oral clarithromycin plus standard-of-care (SoC) antibiotic therapy with placebo plus SoC. The composite endpoint includes any of the following:\n\n* Worsening of the CAP episode, defined as the need to change SoC antibiotic treatment during the first 7 days. A change to moxifloxacin due to detection of atypical pathogens is not considered worsening.\n* Recurrence of CAP symptoms after initial improvement, requiring initiation of new treatment or a change in treatment after Day 7.\n* Any new infection at a non-pulmonary site during the first 28 days.\n* Secondary sepsis occurring between Day 8 and Day 28, defined as the onset of a new infection or recurrence of the CAP episode accompanied by an increase of at least 2 points in the total SOFA-1 score compared with the SOFA-1 score immediately before the new infection or CAP recurrence.","Day 1 through Day 28.",[14,18,22,26,30,33,36,40,44,48,52,56],{"measure":15,"description":16,"timeFrame":17},"All-cause mortality at Day 28","Proportion of participants who die from any cause within 28 days after randomization.","Day 28.",{"measure":19,"description":20,"timeFrame":21},"All-cause mortality at Day 90","Proportion of participants who die from any cause within 90 days after randomization.","Day 90.",{"measure":23,"description":24,"timeFrame":25},"Sepsis response at Day 7","Proportion of participants achieving at least a 25% decrease in the total SOFA-1 score from the pre-treatment Day 1 score by Day 7.","Day 7.",{"measure":27,"description":28,"timeFrame":29},"Type of new sepsis episode","Characterization of new sepsis episodes according to the predominant pathogen and site of infection.","Through Day 28.",{"measure":31,"description":32,"timeFrame":29},"Each of the elements of the composite primary endpoint separately","Incidence of each individual component of the primary composite endpoint, analyzed separately: worsening of the CAP episode, recurrence of CAP symptoms, new infection at a non-pulmonary site, and secondary sepsis.",{"measure":34,"description":35,"timeFrame":29},"Time to antimicrobial escalation","Time from randomization to escalation or change of antimicrobial treatment, measured in days.",{"measure":37,"description":38,"timeFrame":39},"Need for hospital readmission up to day 90","Proportion of participants requiring hospital readmission for any reason following hospital discharge after randomization up to day 90","up to day 90 from enrollment",{"measure":41,"description":42,"timeFrame":43},"Analysis (comparison) of all secondary endpoints for the subgroup of patients (number of patients, %) defined by each physiological parameter that was followed for randomization per investigator site.","Analysis of all secondary endpoints for the subgroups of patients (number of patients, %) defined by each treatment parameter that was followed for randomization per investigator site. The three parameters (treatment pathways) are:\n\n1. oral or iv administration of the investigational medical product (placebo or clarithromycin)\n2. treatment or not with intravenous corticosteroids (total daily dose of at least 200mg hydrocortisone or equivalent)\n3. Absolute lymphocyte count less than 800\u002Fmm³ or between 800 and 1000\u002Fmm³","According to the corresponding secondary endpoint.",{"measure":45,"description":46,"timeFrame":47},"Comparison of outcomes between patients who receive intravenous clarithromycin and patients who receive oral clarithromycin.","Comparison of clinical outcomes (primary and secondary endpoints) between participants receiving intravenous clarithromycin and participants receiving oral clarithromycin.","Through Day 90.",{"measure":49,"description":50,"timeFrame":51},"Patient status self-report documented by the EQ-5D questionnaire or a bespoke visual-analog scale.","Use of standardized questionnaires to measure health-related quality of life","During follow-up through Day 90.",{"measure":53,"description":54,"timeFrame":55},"Incremental cost-effectiveness ratio","Incremental cost-effectiveness ratios (ICERs) comparing clarithromycin plus standard-of-care antibiotic therapy with placebo plus standard-of-care antibiotic therapy, cross-referenced with patient health status.","From day 1 through day 90.",{"measure":57,"description":58,"timeFrame":59},"Biomarkers of sepsis-induced immunoparalysis","Serial assessment of biomarkers associated with sepsis-induced immunoparalysis\u002Fimmunosuppression, including IFN-γ, absolute count of HLA-DR receptors on CD45\u002FCD14-monocytes by flow cytometry. TNF-α production by ex vivo stimulation of peripheral blood monocytes (PBMCs), serum lipids, ferritin, sTREM-1, sTNFR-1, IL-6, IL-8, protein C, and PAI-1.","Study days 1, 4 and 8",[61,64],{"measure":62,"description":63,"timeFrame":25},"Sepsis response by SOFA-2","Proportion of participants achieving at least a 25% decrease in the total SOFA-2 score from the pre-treatment Day 1 score by Day 7.",{"measure":65,"description":66,"timeFrame":29},"Primary endpoint according to baseline IL-6 and IFN-γ levels","Analysis of the primary composite endpoint according to patient subgroups defined by baseline levels of IL-6 and IFN-γ.",{"allocation":68,"interventionModel":69,"interventionModelDescription":70,"primaryPurpose":71,"observationalModel":70,"timePerspective":70,"maskingInfo":72},"RANDOMIZED","PARALLEL",null,"TREATMENT",{"masking":73,"maskingDescription":70,"whoMasked":74},"QUADRUPLE",[75,76,77,78],"PARTICIPANT","CARE_PROVIDER","INVESTIGATOR","OUTCOMES_ASSESSOR","Pneumonia remains the leading cause of sepsis-related deaths worldwide and is one of the primary causes for antimicrobial resistance development. Despite advances in antimicrobial therapy and supportive care, community-acquired pneumonia (CAP) frequently progresses into sepsis and septic shock, resulting in high mortality and prolonged hospitalization.\n\nSepsis is a heterogeneous syndrome, and patients may present different patterns of immune dysfunction. Sepsis-induced immunoparalysis (SII) is characterized by profound downregulation of both innate and adaptive immune responses, with features including decreased monocyte human leukocyte antigen-DR (HLA-DR) expression, lymphopenia, and impaired production of interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). Patients with SII are at increased risk of secondary infections and late mortality.\n\nThere is currently no universally accepted bedside method for identifying SII. Most publications suggest one of the following: exhaustion of peripheral blood mononuclear cells (PBMCs) for the ex vivo production of TNFα, absolute number of HLA-DR receptors on CD14-monocytes less than 8,000\u002Fcell, and blood levels of IFNγ less than 3pg\u002Fml. These methods may be complex and are not widely available in routine clinical practice. Absolute lymphocyte count (ALC) has therefore been proposed as a readily available bedside marker of immune dysfunction. Previous analyses have shown an association between low ALC and SII and adverse outcomes. In particular, an ALC below 800\u002Fmm³ has demonstrated high specificity for SII, while an ALC below 1,000\u002Fmm³ has been associated with increased mortality in hospitalized patients. Other studies have suggested different thresholds, reflecting the lack of an established diagnostic cutoff for SII.\n\nClarithromycin is a macrolide antibiotic with established antimicrobial activity and additional immunomodulatory properties. Previous randomized controlled trials in patients with sepsis have shown that adjunctive clarithromycin may improve laboratory markers of immune dysfunction. These effects have included increased cytokine production by PBMCs and increased expression of HLA-DR on circulating monocytes, consistent with partial reversal of SII. In the randomized controlled trials INCLASS and ACCESS, adjunctive clarithromycin was also associated with a reduction in secondary infections among sepsis survivors. However, SII was not used as an inclusion criterion in these previous studies, and improvement in clinical outcomes was not the primary objective. These findings provide a rationale for evaluating clarithromycin specifically in patients with sepsis and evidence of SII.\n\nThe CLASSIFY trial is designed to determine whether adjunctive treatment with clarithromycin, administered IV or orally, can reduce the incidence of new infection episodes, including secondary sepsis, within 28 days in patients with CAP-RELATED sepsis, and evidence of SII. By focusing on an immunologically defined population, this study aims to validate the immunomodulatory benefit of clarithromycin, clarify its role as an adjunctive therapy for reversing SII, and contribute to precision immunotherapy strategies in sepsis management. The CLASSIFY trial is distinguished by the fact that it introduces the ALC as a beside tool to identify SII and for sensitivity analyses allowing validation of the ALC for diagnosis of SII.\n\nThe primary objective of the CLASSIFY trial is to determine whether clarithromycin added to standard-of-care antibiotic therapy reduces the 28-day incidence of new infections compared with placebo plus standard-of-care antibiotic therapy in patients with CAP-related sepsis and SII. The primary outcome is a composite endpoint including worsening or recurrence of the initial CAP episode, development of a new infection at a non-pulmonary site, and secondary sepsis.\n\nSecondary objectives are to evaluate the effect of clarithromycin on 28-day and 90-day survival, duration of hospitalization, improvement in organ dysfunction after seven days, the relationship between changes in ALC and the development of specific secondary infections, restoration of immunological function, and the cost-effectiveness of treatment. The study will also evaluate biomarkers associated with SII, including IFN-γ, HLA-DR expression, TNF-α production following ex vivo stimulation, serum lipids, ferritin, soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), soluble TNF receptor-1 (sTNFR-1), interleukin-6 (IL-6), interleukin-8 (IL-8), protein C, and plasminogen activator inhibitor-1 (PAI-1).\n\nCLASSIFY is a prospective, multicenter, double-blind, randomized, placebo-controlled Phase III clinical trial that will be conducted at 19 investigator sites in Greece.\n\nAdult patients of either sex hospitalized with CAP and sepsis will be screened for eligibility. CAP will be defined by the presence of a new consolidation on chest imaging in a patient with a compatible clinical presentation, such as fever, dyspnea, cough, or sputum production, without a history of contact with a hospital or healthcare facility for two or more days during the preceding 90 days. Sepsis will be defined according to the Sepsis-3 classification criteria as an increase of at least 2 points in the total Sequential Organ Failure Assessment (SOFA-1) score compared with the patient's baseline score. The CLASSIFY protocol uses SOFA-1 for the definition of sepsis; data required for both SOFA-1 and SOFA-2 will be collected during the study.\n\nEligible participants must have an ALC below 1,000\u002Fmm³. The baseline ALC will be determined from a complete blood count obtained within 48 hours before enrolment. Investigators will make every reasonable effort to determine the patient's pre-existing baseline SOFA-1 score using available medical records and relevant clinical information.\n\nPatients will be excluded if they are younger than 18 years, do not provide informed consent, are pregnant or lactating, or are unwilling to use highly effective contraception during treatment and for seven days following administration of the investigational medicinal product when applicable. Other exclusion criteria include known HIV infection with a CD4 count of 200\u002Fmm³ or less, solid-organ or bone marrow transplantation, significant recent immunosuppressive treatment, recent biological therapy, active malignancy or another condition associated with an expected survival of less than six months, severe neutropenia, treatment with a macrolide for the CAP episode under study, significant QT prolongation or known long QT syndrome, history of macrolide allergy or torsades de pointes, and concomitant use of medications contraindicated with clarithromycin. Patients with severe hypokalemia or hypomagnesemia may become eligible after correction of the electrolyte abnormality. Patients with severe hepatic failure combined with renal impairment, contraindications to macrolide treatment, previous participation in CLASSIFY, or participation in another interventional clinical trial within the preceding 30 days will also be excluded. Finally, patients receiving oral or intravenous corticosteroids greater than 0.4 mg\u002Fkg of equivalent prednisone daily over the last 15 days, or other immunosuppressive therapy. However, corticosteroids received as adjunctive treatment for the current septic\u002F infectious episode are allowed.\n\nFollowing informed consent and confirmation of eligibility, patients will be randomized in a 1:1 ratio to receive either standard-of-care antibiotic therapy plus clarithromycin or standard-of-care antibiotic therapy plus placebo.",[81,87],{"label":82,"type":83,"description":84,"interventionNames":85},"Standard-of-care (SoC) and placebo","PLACEBO_COMPARATOR","In the case of IV placebo medication, patients receive water for injection at a volume of 10ml diluted to a final volume of 250 ml dextrose in water 5%. The duration of the infusion is 1 hour and treatment is given every 12 hours daily for 7 days.\n\nIn the case of oral placebo medication, this is given as oral tablets every 12 hours once for 7 days.\n\nStep-down from IV to oral medication, respectively, is permitted.",[86],"Drug: Placebo",{"label":88,"type":89,"description":90,"interventionNames":91},"Standard-of-care (SoC) and clarithromycin","ACTIVE_COMPARATOR","In the case of IV medication, patients receive 500 mg of clarithromycin diluted with water for injection at a volume of 10ml and further diluted to a final volume of 250 ml dextrose in water 5%. The duration of the infusion is 1 hour and treatment is given every 12 hours daily for 7 days.\n\nIn the case of oral medication, this is given as clarithromycin IR 500mg every 12 hours for 7 days.\n\nStep-down from IV to oral medication, respectively, is permitted.",[92],"Drug: clarithromycin",[94,99],{"type":95,"name":96,"description":97,"armGroupLabels":98,"otherNames":70},"DRUG","Placebo","There is no other intervention in this clinical study and participation in another clinical study is an exclusion criterion.",[82],{"type":95,"name":100,"description":97,"armGroupLabels":101,"otherNames":70},"clarithromycin",[88],[103],{"name":104,"affiliation":5,"role":105},"Evangelos J Giamarellos-Bourboulis, Professor","STUDY_CHAIR",[107],{"name":104,"role":108,"phone":109,"phoneExt":110,"email":111},"CONTACT","2105831994","0030","egiamarel@med.uoa.gr",[113,135,151,164,176,188,200,212,224,237,248,260,275,288,300,312,325,341,354],{"facility":114,"status":115,"city":116,"state":117,"zip":118,"country":119,"countryCode":120,"cosmosGeoPoint":121,"geoPoint":126,"contacts":127},"General University Hospital of Patras, Department of Internal Medicine","RECRUITING","Pátrai","Achaea","265 04","Greece","GR",{"type":122,"coordinates":123},"Point",[124,125],21.73508,38.2462,{"lat":125,"lon":124},[128,132],{"name":129,"role":108,"phone":130,"phoneExt":70,"email":131},"Karolina Akinosoglou, Professor","+306977762897","akin@upatras.gr",{"name":133,"role":134,"phone":70,"phoneExt":70,"email":70},"Karolina Anthoula Akinosoglou, Professor","PRINCIPAL_INVESTIGATOR",{"facility":136,"status":115,"city":137,"state":138,"zip":139,"country":119,"countryCode":120,"cosmosGeoPoint":140,"geoPoint":144,"contacts":145},"Evaggelismos Hospital, 1st Department of Internal Medicine","Athens","Attica","106 76",{"type":122,"coordinates":141},[142,143],23.72784,37.98376,{"lat":143,"lon":142},[146,150],{"name":147,"role":108,"phone":148,"phoneExt":70,"email":149},"Theano Kontopoulou","+306944690525","tkontopoulou@yahoo.gr",{"name":147,"role":134,"phone":70,"phoneExt":70,"email":70},{"facility":152,"status":115,"city":137,"state":138,"zip":153,"country":119,"countryCode":120,"cosmosGeoPoint":154,"geoPoint":156,"contacts":157},"General Hospital of Athens Korgialenio Benakio H.R.C, Intensive Care Unit","115 26",{"type":122,"coordinates":155},[142,143],{"lat":143,"lon":142},[158,162],{"name":159,"role":108,"phone":160,"phoneExt":70,"email":161},"Maria Patrani, MD","+30 6946665991","mpatrani@gmail.com",{"name":163,"role":134,"phone":70,"phoneExt":70,"email":70},"Maria Patrani",{"facility":165,"status":115,"city":137,"state":138,"zip":153,"country":119,"countryCode":120,"cosmosGeoPoint":166,"geoPoint":168,"contacts":169},"General Hospital of Athens Korgialenio Benakio H.R.C., 1st Department of Internal Medicine",{"type":122,"coordinates":167},[142,143],{"lat":143,"lon":142},[170,174],{"name":171,"role":108,"phone":172,"phoneExt":70,"email":173},"Vasiliki Tzavara, MD","+30 6944849808","vtzavara2015@gmail.com",{"name":175,"role":134,"phone":70,"phoneExt":70,"email":70},"Vasiliki Tzavara",{"facility":177,"status":115,"city":137,"state":138,"zip":178,"country":119,"countryCode":120,"cosmosGeoPoint":179,"geoPoint":181,"contacts":182},"General Hospital of Athens G.Gennimatas, 1st Department of Internal Medicine","115 27",{"type":122,"coordinates":180},[142,143],{"lat":143,"lon":142},[183,187],{"name":184,"role":108,"phone":185,"phoneExt":70,"email":186},"Georgios Adamis","+306937463999","geo.adamis@gmail.com",{"name":184,"role":134,"phone":70,"phoneExt":70,"email":70},{"facility":189,"status":115,"city":137,"state":138,"zip":178,"country":119,"countryCode":120,"cosmosGeoPoint":190,"geoPoint":192,"contacts":193},"Thoracic General Hospital of Athens I Sotiria, 3rd University Department of Internal Medicine",{"type":122,"coordinates":191},[142,143],{"lat":143,"lon":142},[194,198],{"name":195,"role":108,"phone":196,"phoneExt":70,"email":197},"Garyfallia Poulakou","+306945597583","gpoulakou@gmail.com",{"name":199,"role":134,"phone":70,"phoneExt":70,"email":70},"Garyfallia Poulakou, Associate Professor",{"facility":201,"status":115,"city":137,"state":138,"zip":178,"country":119,"countryCode":120,"cosmosGeoPoint":202,"geoPoint":204,"contacts":205},"Thoracic General Hospital of Athens I Sotiria, 6th Department of Pulmonary Medicine",{"type":122,"coordinates":203},[142,143],{"lat":143,"lon":142},[206,210],{"name":207,"role":108,"phone":208,"phoneExt":70,"email":209},"Ioannis A. Dimitroulis","+30 6932666007","idimit@hotmail.com",{"name":211,"role":134,"phone":70,"phoneExt":70,"email":70},"Ioannis A Ioannis",{"facility":213,"status":115,"city":137,"state":138,"zip":214,"country":119,"countryCode":120,"cosmosGeoPoint":215,"geoPoint":217,"contacts":218},"General Hospital of Athens Alexandra, Ηigh Dependency Unit of Department of Clinical Therapeutics","115 28",{"type":122,"coordinates":216},[142,143],{"lat":143,"lon":142},[219,223],{"name":220,"role":108,"phone":221,"phoneExt":70,"email":222},"Georgios Dimopoulos, Professor","+306944756565","gdimop@med.uoa.gr",{"name":220,"role":134,"phone":70,"phoneExt":70,"email":70},{"facility":225,"status":115,"city":137,"state":138,"zip":226,"country":119,"countryCode":120,"cosmosGeoPoint":227,"geoPoint":229,"contacts":230},"University General Hospital Attikon-General Hospital of West Attica H Agia Varvara, 2nd Department of Propaedeutic Medicine","124 61",{"type":122,"coordinates":228},[142,143],{"lat":143,"lon":142},[231,235],{"name":232,"role":108,"phone":233,"phoneExt":70,"email":234},"Eleni Boutati","+30 6932434399","eboutati@med.uoa.gr",{"name":236,"role":134,"phone":70,"phoneExt":70,"email":70},"Eleni Boutati, Professor",{"facility":238,"status":115,"city":137,"state":138,"zip":226,"country":119,"countryCode":120,"cosmosGeoPoint":239,"geoPoint":241,"contacts":242},"University General Hospital Attikon-General Hospital of West Attica H Agia Varvara, 4th Department of Internal Medicine",{"type":122,"coordinates":240},[142,143],{"lat":143,"lon":142},[243,246],{"name":244,"role":108,"phone":245,"phoneExt":70,"email":111},"Evangelos J. Giamarellos Bourboulis","+306945521800",{"name":247,"role":134,"phone":70,"phoneExt":70,"email":70},"Antonios Papadopoulos, Professor",{"facility":249,"status":115,"city":137,"state":138,"zip":250,"country":119,"countryCode":120,"cosmosGeoPoint":251,"geoPoint":253,"contacts":254},"General Oncological Hospital of Kifisia Agioi Anargyroi, Intensive Care Unit","145 64",{"type":122,"coordinates":252},[142,143],{"lat":143,"lon":142},[255,259],{"name":256,"role":108,"phone":257,"phoneExt":70,"email":258},"Pavlos Myrianthefs, Professor","+306977774853","pmiriant@nurs.uoa.gr",{"name":256,"role":134,"phone":70,"phoneExt":70,"email":70},{"facility":261,"status":115,"city":262,"state":262,"zip":263,"country":119,"countryCode":120,"cosmosGeoPoint":264,"geoPoint":268,"contacts":269},"University General Hospital of Ioannina, 1st Department of Internal Medicine","Ioannina","455 00",{"type":122,"coordinates":265},[266,267],20.85187,39.66341,{"lat":267,"lon":266},[270,274],{"name":271,"role":108,"phone":272,"phoneExt":70,"email":273},"Charalampos Milionis, Professor","+30 6944521512","hmilioni@uoi.gr",{"name":271,"role":134,"phone":70,"phoneExt":70,"email":70},{"facility":276,"status":277,"city":278,"state":278,"zip":279,"country":119,"countryCode":120,"cosmosGeoPoint":280,"geoPoint":284,"contacts":285},"University General Hospital of Thessaloniki Ahepa, Intensive Care Unit","NOT_YET_RECRUITING","Thessaloniki","546 36",{"type":122,"coordinates":281},[282,283],22.93493,40.64072,{"lat":283,"lon":282},[286],{"name":287,"role":134,"phone":70,"phoneExt":70,"email":70},"Eleni Argyriadou, Professor",{"facility":289,"status":115,"city":278,"state":278,"zip":290,"country":119,"countryCode":120,"cosmosGeoPoint":291,"geoPoint":293,"contacts":294},"Ippokratio General Hospital of Thessaloniki, 2nd Propaedeutic Department of Internal Medicine","546 42",{"type":122,"coordinates":292},[282,283],{"lat":283,"lon":282},[295,299],{"name":296,"role":108,"phone":297,"phoneExt":70,"email":298},"Michael Doumas, Professor","+30 6947006001","michalisdoumas@yahoo.co.uk",{"name":296,"role":134,"phone":70,"phoneExt":70,"email":70},{"facility":301,"status":115,"city":278,"state":278,"zip":302,"country":119,"countryCode":120,"cosmosGeoPoint":303,"geoPoint":305,"contacts":306},"General Hospital of Thessaloniki Papageorgiou, Department of Internal Medicine","564 29",{"type":122,"coordinates":304},[282,283],{"lat":283,"lon":282},[307,311],{"name":308,"role":108,"phone":309,"phoneExt":70,"email":310},"Vasileios Kotsis, Professor","6974748860","vkotsis@auth.gr",{"name":308,"role":134,"phone":70,"phoneExt":70,"email":70},{"facility":313,"status":115,"city":278,"state":278,"zip":314,"country":119,"countryCode":120,"cosmosGeoPoint":315,"geoPoint":317,"contacts":318},"Geniko Nosokomeio Thessalonikis George Papanikolaou, Intensive Care Unit","570 10",{"type":122,"coordinates":316},[282,283],{"lat":283,"lon":282},[319,323],{"name":320,"role":108,"phone":321,"phoneExt":70,"email":322},"Athina Lavrentieva, MD","+306949121458","alavrenti@gmail.com",{"name":324,"role":134,"phone":70,"phoneExt":70,"email":70},"Athina Lavrentieva",{"facility":326,"status":115,"city":327,"state":328,"zip":329,"country":119,"countryCode":120,"cosmosGeoPoint":330,"geoPoint":334,"contacts":335},"University General Hospital of Alexandroupolis, 2nd Department of Internal Medicine","Alexandroupoli","Thrace","681 00",{"type":122,"coordinates":331},[332,333],25.87644,40.84995,{"lat":333,"lon":332},[336,340],{"name":337,"role":108,"phone":338,"phoneExt":70,"email":339},"Periklis Panagopoulos, Professor","+30 6944410495","ppanago@med.duth.gr",{"name":337,"role":134,"phone":70,"phoneExt":70,"email":70},{"facility":342,"status":277,"city":343,"state":344,"zip":345,"country":119,"countryCode":120,"cosmosGeoPoint":346,"geoPoint":350,"contacts":351},"General Hospital of Eleusina Thriasio, 1st Department of Internal Medicine","Elefsina","West Attica","190 18",{"type":122,"coordinates":347},[348,349],23.54295,38.04135,{"lat":349,"lon":348},[352],{"name":353,"role":134,"phone":70,"phoneExt":70,"email":70},"Styliani Sympardi",{"facility":355,"status":277,"city":343,"state":344,"zip":345,"country":119,"countryCode":120,"cosmosGeoPoint":356,"geoPoint":358,"contacts":359},"General Hospital of Eleusina Thriasio, 2nd Department of Internal Medicine",{"type":122,"coordinates":357},[348,349],{"lat":349,"lon":348},[360],{"name":361,"role":134,"phone":70,"phoneExt":70,"email":70},"Konstantina Iliopoulou",{"type":363,"investigatorFullName":70,"investigatorTitle":70,"investigatorAffiliation":70,"oldNameTitle":70,"oldOrganization":70},"SPONSOR","100657176","phase-3-clarithromycin-to-prevent-secondary-infections-in-patients-with-sepsis-following-lower-respiratory-tract-infections-the-classify-trial-100657176",false,"NCT07834346","CLARITHROMYCIN TO PREVENT SECONDARY INFECTIONS IN PATIENTS WITH SEPSIS FOLLOWING LOWER RESPIRATORY TRACT INFECTIONS: THE CLASSIFY TRIAL","CLASSIFY","Inclusion Criteria:\n\n* Age equal to or above 18 years\n* Patients of either gender\n* Written informed consent provided by the patient. For patients without decision-making capacity, informed consent must be obtained from a legally designated representative following the national legislation.\n* Negative (blood or urinary) pregnancy test for female patients of reproductive age\n* For female patients of reproductive age, willingness to use highly effective contraception during and seven days after the administration of the IMP.\n* Presence of Community-acquired pneumonia (CAP)\n* Presence of sepsis as defined by the Sepsis-3 classification criteria (at least 2 points increase of the total SOFA-1 score from the baseline score of the specific patient). The SOFA score which will be used for the definition of sepsis has recently been renamed SOFA-1.\n* Absolute lymphocyte count (ALC) less than 1000\u002Fmm³.\n\nExclusion Criteria:\n\n* Age below 18 years\n* Denial of written informed consent\n* Pregnancy (confirmed by blood or urinary pregnancy test) or lactation for female patients\n* Unwillingness to receive contraception during and seven days after the administration of the IMPstudy drug (for Female patients)\n* Known HIV infection with known CD4 cell count \\\u003C200\u002Fmm³\n* Solid organ or bone marrow transplantation\n* Corticosteroid oral or intravenous intake greater than 0.4mg\u002Fkg of equivalent prednisone daily over the last 15 days or other immunosuppressive therapy. However, corticosteroids received as adjunctive treatment for the current septic\u002Finfectious episode are allowed\n* Intake of a biological agent in the last month\n* Known active neoplasms or other conditions unrelated to sepsis that compromise short-term survival less than 6 months\n* Neutropenia \\\u003C 500\u002Fmm³\n* Intake of any macrolide for the current episode of CAP under study\n* QTc interval at rest in the ECG ≥500 msec or history of known long QT syndrome\n* Medical history of allergy to macrolides\n* Concomitant use of medicinal products contraindicated with clarithromycin, including CYP3A substrates associated with QT prolongation (e.g., astemizole, cisapride, domperidone, pimozide, terfenadine, ivabradine), ergot alkaloids (e.g., ergotamine, dihydroergotamine), oral midazolam, HMG-CoA reductase inhibitors primarily metabolised by CYP3A4 (e.g., lovastatin, simvastatin), colchicine, ticagrelor, and ranolazine. This criterion applies to all medicinal products within these classes, not only the specific examples listed, in accordance with the SmPC for clarithromycin. Patients may be enrolled provided that such medications are discontinued prior to or at the time of trial participation. Given their short half-life, no wash-out period is required\n* Medical history of torsades de pointes arrhythmia\n* Severe hypokalemia or hypomagnesemia; patients may be enrolled once these electrolyte abnormalities are corrected.\n* Any contradictions for macrolide uptake\n* Previous participation in the CLASSIFY study\n* Participation in any other interventional trial within the last 30 days\n* Severe hepatic failure in combination with renal impairment","ALL","18 Years",{"count":374,"type":375},252,"ESTIMATED","INTERVENTIONAL",[378],"PHASE3","The goal of this clinical trial is to assess whether clarithromycin, given as an adjunct to standard-of-care antibiotic therapy, can reduce the risk of new infections and secondary sepsis in adult patients hospitalized with community-acquired pneumonia (CAP), sepsis, and sepsis-induced immunoparalysis (SII). The primary objective is to evaluate the effect of clarithromycin on the incidence of new infection, including worsening or recurrence of the initial CAP episode, new infections at other sites, and secondary sepsis during the 28-day follow-up period. Secondary objectives are to investigate the impact of clarithromycin on mortality, sepsis response, type of secondary infection, time to antimicrobial escalation, hospital readmission, quality of life, cost-effectiveness, and biomarkers of sepsis-induced immunoparalysis.\n\nResearchers will compare clarithromycin plus standard-of-care antibiotic therapy to placebo plus standard-of-care antibiotic therapy.\n\nParticipants will:\n\n* Receive clarithromycin or placebo, administered orally or intravenously, in addition to standard-of-care antibiotic therapy for up to 7 days.\n* Be evaluated during treatment and follow-up through Day 28, with additional assessment of mortality, hospital readmission, and health status through Day 90.",[381],"Sepsis",[383,100,369,384,385,386,387,388],"sepsis","CAP","Community Acquired Pneumonia","SOFA-1","SOFA-2","SII","2026-10-09",{"date":391,"type":392},"2026-10-13","ACTUAL",{"date":394,"type":375},"2026-09",{"date":396,"type":375},"2029-12",{"name":5,"class":6},19]