[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100657698":3},{"organization":4,"outcomesModule":7,"designInfo":48,"detailedDescription":57,"studyPopulation":11,"armGroups":58,"interventions":75,"overallOfficials":89,"centralContacts":93,"locations":102,"responsibleParty":125,"collaborators":11,"id":128,"slug":129,"hasResults":130,"nctId":131,"briefTitle":132,"officialTitle":132,"acronym":133,"eligibilityCriteria":134,"healthyVolunteers":130,"sex":135,"minAge":136,"maxAge":11,"enrollmentInfo":137,"targetDuration":11,"studyType":140,"phases":141,"briefSummary":143,"conditions":144,"keywords":147,"overallStatus":104,"whyStopped":11,"lastUpdateSubmitDate":152,"lastUpdatePostDateStruct":153,"startDateStruct":156,"completionDateStruct":158,"leadSponsor":160,"locationsCount":161},{"fullName":5,"class":6},"Dr Cipto Mangunkusumo General Hospital","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":11},[9],{"measure":10,"description":11,"timeFrame":12},"All-cause mortality",null,"28 days after study enrollment",[14,18,22,26,30,33,37,40,43,46],{"measure":15,"description":16,"timeFrame":17},"Length of hospital stay","Time in days from day of sepsis diagnosis to actual hospital discharge","Within a single hospital admission or within 28 days of sepsis diagnosis",{"measure":19,"description":20,"timeFrame":21},"Diagnostic turnaround time","Time in hours needed from sample collection until the availability of the diagnostic result","Within 28 days of study enrollment, or within the same hospital stay",{"measure":23,"description":24,"timeFrame":25},"Duration of antimicrobial therapy","Time in days from initiation of antimicrobial therapy indicated for sepsis during hospital stay until discontinuation of antimicrobial therapy","From study enrollment up to 28 days after enrollment, within a single hospital stay and one episode of sepsis",{"measure":27,"description":28,"timeFrame":29},"Time from empirical antimicrobial therapy to definitive therapy","Time in days from empirical antimicrobial therapy initiation to definitive therapy initiation","Within same hospital stay, from enrollment up to 28 days",{"measure":31,"description":32,"timeFrame":12},"Use of mechanical ventilation within 28 days of enrollment","Number of participants with mechanical ventilation",{"measure":34,"description":35,"timeFrame":36},"Total cost of hospitalization per participant","total in IDR, from a single hospital stay where patient is enrolled in study","Within a single hospital stay during study enrollment",{"measure":38,"description":11,"timeFrame":39},"Total Diagnostic Cost per Participant for Hybrispot DNA Flow and 16S rRNA Metagenomics Compared With Conventional Blood Culture","From study enrollment to completion of diagnostic testing within a single hospital stay",{"measure":41,"description":11,"timeFrame":42},"Number of participants admitted to the ICU","28 days after study enrollment, within a single hospital stay",{"measure":44,"description":11,"timeFrame":45},"Rate of participants with pathogen identification by Hybrispot DNA Flow compared to conventional blood culture","Within a single hospital stay, or 28 days after study enrollment",{"measure":47,"description":11,"timeFrame":45},"Rate of participants with pathogen identification by 16S rRNA Metagenomics compared to conventional blood culture",{"allocation":49,"interventionModel":50,"interventionModelDescription":11,"primaryPurpose":51,"observationalModel":11,"timePerspective":11,"maskingInfo":52},"RANDOMIZED","PARALLEL","DIAGNOSTIC",{"masking":53,"maskingDescription":11,"whoMasked":54},"DOUBLE",[55,56],"PARTICIPANT","OUTCOMES_ASSESSOR","Background Sepsis is an important global health problem, with 49.9 million cases and 11 million sepsis-related deaths reported during 1990-2017. Approximately 85% of sepsis cases and sepsis-related deaths worldwide occur in low- and middle-income countries, including Indonesia, which accounts for approximately 64% of sepsis cases, with mortality reaching 69%.\n\nAntimicrobial therapy is a critical component of sepsis management and should be initiated as soon as possible after sepsis is diagnosed. In practice, however, antimicrobial treatment may be delayed or used excessively for several reasons. Delays may occur because of difficulties in accurately diagnosing sepsis, particularly in cases with atypical presentations. Access to antimicrobials may also be limited. Conversely, broad-spectrum antimicrobials may be overused, including in cases that do not involve sepsis. Both situations may result in short-term adverse effects, such as drug reactions or allergies, and long-term consequences, including antimicrobial resistance.\n\nTherefore, rapid and accurate diagnosis of sepsis, together with identification of the causative microorganisms, is essential. The conventional method for identifying microorganisms in the blood is blood culture, in which microorganisms are grown in culture media. This process may require 5 - 7 days from blood collection to final results.\n\nThis study will investigate the efficacy of diagnostic tools for identifying microorganisms causing sepsis using polymerase chain reaction (PCR), specifically Hybrispot DNA Flow, and 16S rRNA metagenomics. Hybrispot DNA Flow combines multiplex PCR and flow-through hybridization to enable rapid simultaneous detection of multiple pathogens and antimicrobial resistance genes in a shorter time than conventional culture. In addition, the 16S rRNA metagenomic approach enables comprehensive identification of microorganisms without requiring culture, including fastidious bacteria, low-abundance microorganisms, and unexpected pathogens. This approach may also provide broader information regarding microbiota composition, virulence factors, and antimicrobial resistance determinants that may contribute to disease progression.\n\nObjectives\n\n1. To identify patterns of pathogens causing sepsis and antimicrobial resistance characteristics based on conventional culture, Hybrispot DNA Flow, and 16S rRNA metagenomic testing.\n2. To compare the ability of conventional culture, Hybrispot DNA Flow, and 16S rRNA metagenomics to detect pathogens and antimicrobial resistance determinants.\n3. To compare the turnaround time required to obtain diagnostic results using conventional culture, Hybrispot DNA Flow, and 16S rRNA metagenomics.\n4. To evaluate the effect of Hybrispot DNA Flow and 16S rRNA metagenomics on accelerating the transition from empirical to definitive antimicrobial therapy compared with conventional culture.\n5. To compare clinical outcomes among patients undergoing genomic-based testing and conventional culture, including:\n\n   * Duration of antimicrobial therapy\n   * Length of hospital stay\n   * Hospitalization costs\n   * All-cause mortality\n   * Adverse clinical outcomes, including the need for mechanical ventilation, ICU admission, and vasopressor use.\n\nStudy Design\n\nThis study is a randomized, parallel-arm, single-blinded, single-center clinical trial.\n\nSample Size\n\nThe sample size was calculated to compare mean outcomes between the conventional culture group and the molecular\u002Fgenomic diagnostic groups, using a significance level (α) of 5%, 80% power, a group ratio of 2:1:1, a standard deviation (σ) of 48, and a minimum clinically significant mean difference (δ) of 12.\n\nThe calculation resulted in 188 participants in the Standard-of-Care group, 94 participants (n1\u002F2) in the PCR group, and 94 participants in the Metagenomics group, for a total of 376 participants.\n\nAfter accounting for a potential 10% dropout rate, the minimum required sample size is 207 participants in the Standard-of-Care group, 104 participants in the PCR group, and 104 participants in the Metagenomics group, for a total of 415 participants.\n\nProcedures \u002F Study Flow\n\n1. Patients who meet the inclusion criteria and agree to participate will be recruited as study participants.\n2. Block randomization will be performed by the laboratory team to alocate the participants into Standard-of-Care, PCR, or Metagenomics group in a 2:1:1 ratio.\n3. In the Standard-of-Care group, blood culture will be performed for identification and antimicrobial susceptibility testing as standard care in accordance with the hospital's current standard operating procedures (SOPs).\n4. In the PCR group, multiplex PCR will be performed in addition to standard care using standard blood culture. Blood samples will be incubated using BACT\u002FALERT system. As soon as a signal is detected from the respective sample (either positive or negative signal), multiplex PCR using Hybrispot will be performed.\n5. In the Metagenomics group, 16s metagenomic will be performed in addition to standard care using standard blood culture. Following blood collection in an EDTA tube, DNA extraction, targeted PCR, electrophoresis, and metagenomic NGS will be performed. Only PCR-positive sample will continue to the mNGS process. PCR-negative sample will be reported as negative.\n6. Any remaining specimens will be destroyed in accordance with the laboratory's Standard Operating Procedures (SOPs).\n7. Blood culture results will be reported to the treating physician in accordance with standard clinical practice. Results from PCR and metagenomic testing will be reported as additional findings to the treating physician. Treatment decisions will remain at the discretion of the treating physician in accordance with standard clinical care.\n8. All participants will be followed until the predefined study outcomes have been assessed, including diagnostic results and relevant clinical outcomes.\n\nStudy Parameters\n\nIndependent variables:\n\n* Conventional microbiological culture and antimicrobial susceptibility testing as standard care.\n* Multiplex PCR and flow-through hybridization for pathogen identification and detection of antimicrobial resistance genes based on the test panel in addition to conventional microbiological culture and antimicrobial susceptibility testing.\n* Metagenomic testing for pathogen identification and detection of antimicrobial resistance genes in addition to conventional microbiological culture and antimicrobial susceptibility testing.\n\nDependent variables:\n\nDiagnostic outcomes\n\n* Identification of causative pathogens.\n* Detection of antimicrobial resistance determinants.\n* Diagnostic turnaround time.\n* Additional diagnostic yield of Hybrispot DNA Flow and 16S rRNA metagenomics compared with conventional culture.\n\nClinical outcomes:\n\n* Transition time from empirical to definitive antimicrobial therapy.\n* Duration of antimicrobial therapy.\n* Length of hospital stay.\n* All-cause mortality.\n* Adverse clinical outcomes, including the need for mechanical ventilation, ICU admission, and vasopressor use.\n* Antimicrobial therapy-related adverse events.\n\nEconomic outcomes:\n\n* Hospitalization costs.\n* Potential cost efficiency associated with the use of genomic-based diagnostics.\n\nData and Statistical Analysis\n\nStudy data will be processed electronically using SPSS version 23.0. Clinical and participant characteristics will be presented in tables. Numerical descriptive data will be presented as point estimates and interval estimates. Normally distributed data will be presented as mean and standard deviation (SD), while non-normally distributed data will be presented as median and interquartile range (IQR). Categorical data will be presented as counts and percentages. Comparisons between groups will be performed by comparing proportions and means between the groups.\n\nBenefits\n\nThe study is expected to provide several important benefits for both patient care and the development of infection diagnostics at RSCM. By generating genomic data on pathogens and antimicrobial resistance, the study may contribute to the characterization of local epidemiology, including resistance gene profiles, virulence factors, and patterns of microorganism transmission within the hospital environment. The implementation of genomic-based diagnostic technologies may also improve the speed and accuracy of pathogen identification, facilitating more targeted antimicrobial therapy and earlier transition from empirical to definitive treatment, with the potential to improve clinical outcomes. Furthermore, the molecular data generated may strengthen RSCM's Antimicrobial Stewardship (AMS), antimicrobial resistance (AMR) surveillance, and infection prevention and control (IPC) programs by supporting clinical decision-making, outbreak investigation, and the development of evidence-based antimicrobial-use policies. Finally, by evaluating the clinical and health-economic benefits of Hybrispot DNA Flow and 16S rRNA metagenomics, this study may provide a scientific basis for the development and integration of genomic diagnostic services at RSCM and support its role as a national referral hospital advancing precision medicine and molecular data-driven healthcare.",[59,65,70],{"label":60,"type":61,"description":62,"interventionNames":63},"Standard-of-care","EXPERIMENTAL","Blood culture will be performed for identification and antimicrobial susceptibility testing as standard care in accordance with the hospital's current standard operating procedures (SOPs).",[64],"Diagnostic Test: Standard-of-care blood culture",{"label":66,"type":61,"description":67,"interventionNames":68},"PCR","Multiplex PCR will be performed in addition to standard care using standard blood culture. Blood samples will be incubated using BACT\u002FALERT system. As soon as a signal is detected from the respective sample (either positive or negative signal), multiplex PCR using Hybrispot will be performed.",[64,69],"Diagnostic Test: Hybrispot DNA Flow",{"label":71,"type":61,"description":72,"interventionNames":73},"Metagenomic","16s metagenomic will be performed in addition to standard care using standard blood culture. Following blood collection in an EDTA tube, DNA extraction, targeted PCR, electrophoresis, and metagenomic NGS will be performed. Only PCR-positive sample will continued to the mNGS process. PCR-negative sample will be reported as negative.",[64,74],"Diagnostic Test: Metagenomic 16s RNA",[76,81,85],{"type":77,"name":78,"description":79,"armGroupLabels":80,"otherNames":11},"DIAGNOSTIC_TEST","Standard-of-care blood culture","Participants will undergo standard blood culture using the BACT\u002FALERT system. Cultures will be monitored until a final result of either microbial growth or no growth is obtained.",[71,66,60],{"type":77,"name":82,"description":83,"armGroupLabels":84,"otherNames":11},"Hybrispot DNA Flow","Hybrispot DNA Flow is a diagnostic tool combining multiplex polymerase chain reaction (PCR) and flow-through hybridization.",[66],{"type":77,"name":86,"description":87,"armGroupLabels":88,"otherNames":11},"Metagenomic 16s RNA","The metagenomic approach using the 16S rRNA platform enables comprehensive identification of microorganisms, including fastidious bacteria, low-abundance microorganisms, and unexpected or previously unrecognized pathogens.",[71],[90],{"name":91,"affiliation":5,"role":92},"Robert Sinto, MD, MSc.Clin.Ed, D.Phil","PRINCIPAL_INVESTIGATOR",[94,98],{"name":91,"role":95,"phone":96,"phoneExt":11,"email":97},"CONTACT","+628158835432","robert.sinto01@ui.ac.id",{"name":99,"role":95,"phone":100,"phoneExt":11,"email":101},"Selvi N Shahab, MD","+6285770564595","selvishahab@rscm.co.id",[103],{"facility":5,"status":104,"city":105,"state":106,"zip":107,"country":108,"countryCode":109,"cosmosGeoPoint":110,"geoPoint":115,"contacts":116},"RECRUITING","Jakarta","DKI Jakarta","10430","Indonesia","ID",{"type":111,"coordinates":112},"Point",[113,114],106.84513,-6.21462,{"lat":114,"lon":113},[117,118,120,123],{"name":91,"role":95,"phone":96,"phoneExt":11,"email":97},{"name":119,"role":92,"phone":11,"phoneExt":11,"email":11},"Robet Sinto, MD, MSc.Clin.Ed, D.Phil",{"name":121,"role":122,"phone":11,"phoneExt":11,"email":11},"Sharifah Shakinah, MD","SUB_INVESTIGATOR",{"name":124,"role":122,"phone":11,"phoneExt":11,"email":11},"Adeline Pasaribu, MD",{"type":92,"investigatorFullName":126,"investigatorTitle":127,"investigatorAffiliation":5,"oldNameTitle":11,"oldOrganization":11},"Robert Sinto","Principal Investigator","100657698","molecular-based-optimization-of-pathogen-identification-in-sepsis-patients-in-the-indonesian-national-referral-hospital-100657698",false,"NCT07841535","Molecular-based Optimization of Pathogen Identification in Sepsis Patients in the Indonesian National Referral Hospital","INA-MOSAIC","Inclusion Criteria:\n\n* Age ≥18 years.\n* Sepsis or septic shock according to Sepsis-3 criteria, defined as suspected or confirmed infection with acute organ dysfunction (SOFA score increase ≥2 points from baseline) within 24 hours of inclusion.\n* Hospitalized at RSCM and undergoing microbiological testing, including blood culture as part of standard care.\n* At least one risk factor for multidrug-resistant (MDR) pathogens according to the 2026 Surviving Sepsis Campaign, including:\n\n  * Previous colonization or infection with a relevant MDR pathogen.\n  * Prolonged exposure to broad-spectrum antibiotics.\n  * Prolonged hospitalization in a setting with a high prevalence of MDR pathogens, such as the ICU or a ward with a high antimicrobial resistance burden.\n* Written informed consent from the patient or legal representative, where applicable for prospective enrollment.\n\nExclusion Criteria:\n\n* Unable to provide specimens according to the study protocol.\n* Received intravenous antimicrobial regimen for more than 24 hours prior to study enrollment, with the regimen continued as empirical therapy for the current sepsis diagnosis.\n* Opt out of best treatment according to medical advice.\n\nDropout criteria:\n\n\\- Discharge from the hospital or death within 24 hours after blood collection.","ALL","18 Years",{"count":138,"type":139},415,"ESTIMATED","INTERVENTIONAL",[142],"NA","This study aims to compare the diagnostic performance of conventional blood culture with two molecular-based diagnostic approaches, Hybrispot DNA Flow and metagenomic next-generation sequencing (mNGS), for the identification of microorganisms in patients with sepsis. The study will evaluate the turnaround time of each diagnostic method and assess their potential impact on the time to definitive antimicrobial therapy and subsequent clinical outcomes.\n\nThe study is led by Robert Sinto, an infectious disease physician at Dr. Cipto Mangunkusumo National Referral Hospital (RSCM), the national referral hospital in Indonesia.\n\nConventional blood culture, which serves as the standard microbiological diagnostic method, may require about 5 to 7 days to obtain a final result. In comparison, Hybrispot DNA Flow and mNGS detect microbial genetic material and may provide microbiological results within approximately 2 to 3 days. By comparing these diagnostic strategies, the study seeks to determine whether molecular-based approaches can facilitate more rapid pathogen identification and support earlier optimization of antimicrobial therapy.\n\nParticipation in the study is voluntary. Participants may withdraw from the study at any time without affecting the medical care they receive. Participants may also request information about their diagnostic results and may ask the research team to clarify any aspect of the study that they do not understand.",[145,146],"Sepsis","Antimicrobial Resistance (AMR)",[145,148,149,150,151],"Molecular","antimicrobial resistance","diagnostic stewardship","metagenomic","2026-09-20",{"date":154,"type":155},"2026-09-25","ACTUAL",{"date":157,"type":155},"2026-09-01",{"date":159,"type":139},"2027-12-31",{"name":5,"class":6},1]