Ignite Creation Date:
2026-03-26 @ 3:17 PM
Ignite Modification Date:
2026-03-29 @ 11:58 PM
Study NCT ID:
NCT07442032
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-03-02
First Post:
2025-12-16
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Cardiovascular Phenotypes in Sepsis
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'conditionBrowseModule': {'meshes': [{'id': 'D018805', 'term': 'Sepsis'}, {'id': 'D012772', 'term': 'Shock, Septic'}], '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'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITHOUT_DNA', 'description': 'Venous blood samples (approximately 30 mL) will be collected within 72 hours of admission and again at the 3-month follow-up visit. Samples will be processed and stored at -80°C for later analysis of inflammatory, endothelial, glycocalyx, microvascular, and thrombotic biomarkers.'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 400}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-04-06', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-02', 'completionDateStruct': {'date': '2029-12-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-02-26', 'studyFirstSubmitDate': '2025-12-16', 'studyFirstSubmitQcDate': '2026-02-26', 'lastUpdatePostDateStruct': {'date': '2026-03-02', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-03-02', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2028-05-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Cardiovascular events during one-year follow-up after critical care admission', 'timeFrame': 'From admission to the IMCU/ICU/CCU through 1 year after admission', 'description': 'Cardiovascular events, including myocardial infarction, hospitalization for heart failure, and newly diagnosed clinically significant arrhythmias, will be recorded from admission to the IMCU/ICU/CCU through 1 year of follow-up.'}], 'primaryOutcomes': [{'measure': 'Association between cardiovascular phenotypes and one-year mortality in sepsis', 'timeFrame': 'Up to 1 year after admission to the Intermediate Care Unit (IMCU), Intensive Care Unit (ICU) or Cardiac Care Unit (CCU).', 'description': 'To assess the association between distinct cardiovascular phenotypes and one-year mortality in patients with sepsis. Cardiovascular phenotypes will be categorized as: (a) peripheral circulatory dysfunction (present vs. absent), (b) heart failure (present vs. absent), and (c) the combined presence of peripheral circulatory dysfunction and heart failure. One-year mortality will be analyzed according to phenotype group.'}], 'secondaryOutcomes': [{'measure': 'Association between cardiovascular phenotypes and in-hospital mortality in sepsis', 'timeFrame': 'From admission to the IMCU, ICU, or CCU (baseline) until the date of in-hospital death or hospital discharge, whichever occurs first, assessed up to 90 days.', 'description': 'To assess the association between distinct cardiovascular phenotypes and in-hospital mortality in patients with sepsis. Cardiovascular phenotypes will be categorized as: (a) peripheral circulatory dysfunction (present vs. absent), (b) heart failure (present vs. absent), and (c) the combined presence of peripheral circulatory dysfunction and heart failure. In-hospital mortality will be analyzed according to phenotype group.'}, {'measure': 'Change in echocardiographic indices of acute ventricular function and ventriculo-arterial coupling from baseline to 3 months', 'timeFrame': 'Baseline (within 72 hours of admission to the IMCU/ICU/CCU) to 3 months after baseline.', 'description': 'Transthoracic echocardiographic assessment of acute ventricular function and ventriculo-arterial coupling performed during the index hospitalization and at 3 months after baseline. Measurements may include conventional and advanced indices of left ventricular function, right ventricular function, and biventricular ventriculo-arterial coupling derived from standard echocardiographic views and Doppler measurements. Individual echocardiographic parameters will be reported separately as continuous or dichotomous variables, as appropriate. Changes in individual echocardiographic parameters from baseline to 3-month follow-up will be analyzed.'}, {'measure': 'Association of integrated cardiovascular biomarkers with one-year and in-hospital mortality in sepsis', 'timeFrame': 'Up to 1 year after admission to the IMCU/ICU/CCU (baseline)', 'description': 'Cardiovascular phenotypes will be refined by integrating established cardiac biomarkers, including high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), together with serum markers of endothelial dysfunction and pro-coagulant activity. The association between biomarker-refined cardiovascular phenotypes and mortality will be evaluated to assess their prognostic value.'}, {'measure': 'Association between emerging cardiovascular biomarkers and myocardial injury severity in sepsis', 'timeFrame': '0-72 hours after admission to the IMCU/ICU/CCU', 'description': 'Emerging cardiovascular biomarkers will be measured in patients with sepsis using one blood sample obtained within 0-72 hours of admission to the IMCU/ICU/CCU. Biomarker levels will be analyzed in relation to the severity and progression of myocardial injury, as assessed by the established myocardial injury marker high-sensitivity cardiac troponin T (hs-cTnT) and relevant clinical parameters assessed within 0-72 hours of admission to the IMCU/ICU/CCU.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Sepsis', 'septic shock', 'cardiovascular dysfunction', 'microcirculatory dysfunction', 'cardiac biomarkers', 'troponin', 'peripheral arterial tonometry', 'echocardiography'], 'conditions': ['Sepsis', 'Septic Shock', 'Cardiovascular Dysfunction', 'Microcirculatory Dysfunction', 'Troponin Elevation', 'Peripheral Vascular Response']}, 'referencesModule': {'references': [{'pmid': '34784496', 'type': 'BACKGROUND', 'citation': 'Frencken JF, van Smeden M, van de Groep K, Ong DSY, Klein Klouwenberg PMC, Juffermans N, Bonten MJM, van der Poll T, Cremer OL; MARS Consortium. Etiology of Myocardial Injury in Critically Ill Patients with Sepsis: A Cohort Study. Ann Am Thorac Soc. 2022 May;19(5):773-780. doi: 10.1513/AnnalsATS.202106-689OC.'}, {'pmid': '31046824', 'type': 'BACKGROUND', 'citation': 'Tyden H, Lood C, Jonsen A, Gullstrand B, Kahn R, Linge P, Kumaraswamy SB, Dahlback B, Bengtsson AA. Low plasma concentrations of apolipoprotein M are associated with disease activity and endothelial dysfunction in systemic lupus erythematosus. Arthritis Res Ther. 2019 May 2;21(1):110. doi: 10.1186/s13075-019-1890-2.'}, {'pmid': '23318492', 'type': 'BACKGROUND', 'citation': 'De Backer D, Donadello K, Sakr Y, Ospina-Tascon G, Salgado D, Scolletta S, Vincent JL. Microcirculatory alterations in patients with severe sepsis: impact of time of assessment and relationship with outcome. Crit Care Med. 2013 Mar;41(3):791-9. doi: 10.1097/CCM.0b013e3182742e8b.'}, {'pmid': '24365861', 'type': 'BACKGROUND', 'citation': 'Landesberg G, Jaffe AS, Gilon D, Levin PD, Goodman S, Abu-Baih A, Beeri R, Weissman C, Sprung CL, Landesberg A. Troponin elevation in severe sepsis and septic shock: the role of left ventricular diastolic dysfunction and right ventricular dilatation*. Crit Care Med. 2014 Apr;42(4):790-800. doi: 10.1097/CCM.0000000000000107.'}, {'pmid': '28884343', 'type': 'BACKGROUND', 'citation': 'Vallabhajosyula S, Kumar M, Pandompatam G, Sakhuja A, Kashyap R, Kashani K, Gajic O, Geske JB, Jentzer JC. Prognostic impact of isolated right ventricular dysfunction in sepsis and septic shock: an 8-year historical cohort study. Ann Intensive Care. 2017 Sep 7;7(1):94. doi: 10.1186/s13613-017-0319-9.'}, {'pmid': '25800584', 'type': 'BACKGROUND', 'citation': 'Sanfilippo F, Corredor C, Fletcher N, Landesberg G, Benedetto U, Foex P, Cecconi M. Diastolic dysfunction and mortality in septic patients: a systematic review and meta-analysis. Intensive Care Med. 2015 Jun;41(6):1004-13. doi: 10.1007/s00134-015-3748-7. Epub 2015 Mar 24.'}, {'pmid': '29361252', 'type': 'BACKGROUND', 'citation': 'Vallabhajosyula S, Pruthi S, Shah S, Wiley BM, Mankad SV, Jentzer JC. Basic and advanced echocardiographic evaluation of myocardial dysfunction in sepsis and septic shock. Anaesth Intensive Care. 2018 Jan;46(1):13-24. doi: 10.1177/0310057X1804600104.'}, {'pmid': '36722388', 'type': 'BACKGROUND', 'citation': 'Jentzer JC, Lawler PR, Van Houten HK, Yao X, Kashani KB, Dunlay SM. Cardiovascular Events Among Survivors of Sepsis Hospitalization: A Retrospective Cohort Analysis. J Am Heart Assoc. 2023 Feb 7;12(3):e027813. doi: 10.1161/JAHA.122.027813. Epub 2023 Feb 1.'}, {'pmid': '20938765', 'type': 'BACKGROUND', 'citation': 'Rosjo H, Varpula M, Hagve TA, Karlsson S, Ruokonen E, Pettila V, Omland T; FINNSEPSIS Study Group. Circulating high sensitivity troponin T in severe sepsis and septic shock: distribution, associated factors, and relation to outcome. Intensive Care Med. 2011 Jan;37(1):77-85. doi: 10.1007/s00134-010-2051-x. Epub 2010 Oct 12.'}, {'pmid': '37156347', 'type': 'BACKGROUND', 'citation': 'Lorstad S, Shekarestan S, Jernberg T, Tehrani S, Astrand P, Gille-Johnson P, Persson J. First Sampled High-Sensitive Cardiac Troponin T is Associated With One-Year Mortality in Sepsis Patients and 30- to 365-Day Mortality in Sepsis Survivors. Am J Med. 2023 Aug;136(8):814-823.e8. doi: 10.1016/j.amjmed.2023.04.029. Epub 2023 May 6.'}, {'pmid': '28889100', 'type': 'BACKGROUND', 'citation': 'Vallabhajosyula S, Sakhuja A, Geske JB, Kumar M, Poterucha JT, Kashyap R, Kashani K, Jaffe AS, Jentzer JC. Role of Admission Troponin-T and Serial Troponin-T Testing in Predicting Outcomes in Severe Sepsis and Septic Shock. J Am Heart Assoc. 2017 Sep 9;6(9):e005930. doi: 10.1161/JAHA.117.005930.'}, {'pmid': '30153967', 'type': 'BACKGROUND', 'citation': 'Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). J Am Coll Cardiol. 2018 Oct 30;72(18):2231-2264. doi: 10.1016/j.jacc.2018.08.1038. Epub 2018 Aug 25. No abstract available.'}, {'pmid': '29278915', 'type': 'BACKGROUND', 'citation': 'Mair J, Lindahl B, Hammarsten O, Muller C, Giannitsis E, Huber K, Mockel M, Plebani M, Thygesen K, Jaffe AS. How is cardiac troponin released from injured myocardium? Eur Heart J Acute Cardiovasc Care. 2018 Sep;7(6):553-560. doi: 10.1177/2048872617748553. Epub 2017 Dec 27.'}, {'pmid': '35972428', 'type': 'BACKGROUND', 'citation': 'Hammarsten O, Wernbom M, Mills NL, Mueller C. How is cardiac troponin released from cardiomyocytes? Eur Heart J Acute Cardiovasc Care. 2022 Sep 29;11(9):718-720. doi: 10.1093/ehjacc/zuac091. No abstract available.'}, {'pmid': '27011791', 'type': 'BACKGROUND', 'citation': 'Kakihana Y, Ito T, Nakahara M, Yamaguchi K, Yasuda T. Sepsis-induced myocardial dysfunction: pathophysiology and management. J Intensive Care. 2016 Mar 23;4:22. doi: 10.1186/s40560-016-0148-1. eCollection 2016.'}, {'pmid': '31151462', 'type': 'BACKGROUND', 'citation': 'Vincent JL, Jones G, David S, Olariu E, Cadwell KK. Frequency and mortality of septic shock in Europe and North America: a systematic review and meta-analysis. Crit Care. 2019 May 31;23(1):196. doi: 10.1186/s13054-019-2478-6.'}, {'pmid': '26903338', 'type': 'BACKGROUND', 'citation': 'Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.'}]}, 'descriptionModule': {'briefSummary': 'This prospective observational study will investigate cardiovascular phenotypes in adults with sepsis and hemodynamic instability. Approximately 400 patients requiring vasopressor support will be enrolled across multiple hospital sites. Within 72 hours of admission, participants will undergo peripheral vascular assessments, echocardiography, and blood sampling for cardiac, endothelial, and inflammatory biomarkers. Patients will be classified according to the presence or absence of peripheral vascular dysfunction and cardiac dysfunction. The primary aim is to examine the association between these cardiovascular phenotypes and one-year mortality. Secondary aims include evaluating biomarker profiles, characterizing myocardial injury, and assessing cardiac function at a 3-month follow-up. The study seeks to improve understanding of sepsis-related cardiovascular dysfunction and support development of more individualized management strategies.', 'detailedDescription': 'Sepsis is frequently accompanied by myocardial injury, myocardial dysfunction, and peripheral circulatory abnormalities, all of which contribute to hemodynamic instability and increased mortality. Despite their clinical importance, distinct cardiovascular phenotypes in sepsis have not been clearly defined, and no established guidelines exist for evaluating or managing sepsis-related myocardial dysfunction. This study aims to characterize cardiovascular phenotypes based on peripheral vascular function and cardiac performance, and to assess their association with clinical outcomes.\n\nThis is a prospective, multicenter observational cohort study enrolling 400 adults with suspected sepsis and hemodynamic instability requiring vasopressor support. Eligible patients will be included within 72 hours of admission to an Intermediate Care Unit, Intensive Care Unit, Cardiac Care Unit, or Acute Care Unit. After enrollment, participants will undergo standardized assessments of peripheral endothelial function using the EndoPAT device and capillary refill time measurement. A comprehensive echocardiographic evaluation will be performed to assess biventricular function and left-a dn right ventricular-arterial coupling. Blood samples will be collected and stored for analysis of cardiac biomarkers (including high-sensitivity cardiac troponin and NT-proBNP), as well as inflammatory, endothelial, glycocalyx, and thrombotic biomarkers.\n\nParticipants will be classified into cardiovascular phenotypes: ; i) peripheral vascular dysfunction, ii) cardiac dysfunction, iii) a combination of peripheral vascular dysfunction and cardiac dysfunction or iv) no dysfunction. The primary objective is to evaluate the association between these phenotypes and one-year all-cause mortality using survival analysis methods such ax Cox regression. Secondary objectives include examining biomarker patterns associated with cardiovascular dysfunction, assessing the severity and progression of myocardial injury, and evaluating changes in cardiac function at a three-month follow-up visit where repeat EndoPAT testing, capillary refill time assessment, echocardiography, and blood sampling will be performed.\n\nLong-term clinical outcomes, including cardiovascular events and mortality, will be obtained through the electronic health register. The study aims to improve understanding of the interplay between microcirculatory dysfunction, myocardial injury, and cardiac performance in sepsis, and to support development of individualized risk stratification and future clinical management strategies.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Adult patients with suspected sepsis and hemodynamic instability requiring vasopressor support, recruited across multiple hospital critical care units including the Intermediate Care Unit (IMCU), Intensive Care Unit (ICU), Cardiac Care Unit (CCU) and Acute Care Unit (ACU).', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age 18 years or older\n* Suspected sepsis based on clinical evaluation and supporting laboratory findings\n* Hemodynamic instability, defined as mean arterial pressure \\< 65 mmHg despite adequate fluid resuscitation\n* Requirement for vasopressor support\n* Inclusion within 72 hours of admission to an Intermediate Care Unit (IMCU), Intensive Care Unit (ICU), Cardiac Care Unit (CCU), or Acute Care Unit (ACU)\n\nExclusion Criteria:\n\n* Lack of informed consent\n* Advanced peripheral arterial disease, including: subclavian artery occlusion with vertebrobasilar symptoms, critical hand ischemia with tissue loss or non-healing wounds, multilevel occlusive disease affecting upper-extremity arteries, upper limb surgery or significant upper limb trauma within 30 days prior to admission, technical limitations preventing proper placement of the EndoPAT device (e.g., finger amputation, severe rheumatologic deformity, or marked extremity edema).'}, 'identificationModule': {'nctId': 'NCT07442032', 'acronym': 'CaPS', 'briefTitle': 'Cardiovascular Phenotypes in Sepsis', 'organization': {'class': 'OTHER', 'fullName': 'Karolinska Institutet'}, 'officialTitle': 'Cardiovascular Phenotypes in Sepsis', 'orgStudyIdInfo': {'id': 'CaPS'}, 'secondaryIdInfos': [{'id': 'Dnr 2025-04572-01', 'type': 'REGISTRY', 'domain': 'Swedish Ethics Review Authority (Etikprövningsmyndigheten)'}]}, 'armsInterventionsModule': {'armGroups': [{'label': 'Adults with suspected sepsis and hemodynamic instability requiring vasopressor support.', 'description': 'Participants are enrolled prospectively across multiple hospital sites and undergo standardized assessments of peripheral vascular function, echocardiography, and biomarker sampling. No interventions are assigned as part of the study.'}]}, 'contactsLocationsModule': {'centralContacts': [{'name': 'Jonas Persson, M.D., PhD', 'role': 'CONTACT', 'email': 'jonas.persson@regionstockholm.se', 'phone': '+46 (0) 700 891412'}, {'name': 'Samantha Lörstad, M.D.', 'role': 'CONTACT', 'email': 'samantha.rutherford-lorstad@regionstockholm.se', 'phone': '+46 (0) 708 693973'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Karolinska Institutet', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'MD PhD', 'investigatorFullName': 'Jonas Persson', 'investigatorAffiliation': 'Karolinska Institutet'}}}}