Ignite Creation Date:
2025-12-26 @ 11:10 AM
Ignite Modification Date:
2025-12-28 @ 9:13 PM
Study NCT ID:
NCT04593212
Status:
UNKNOWN
Last Update Posted:
2023-09-28
First Post:
2020-10-13
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Assessment of Microcirculatory Dysfunction in Septic Shock Patients by OCTA
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D012772', 'term': 'Shock, Septic'}], 'ancestors': [{'id': 'D018805', 'term': 'Sepsis'}, {'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': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 165}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'RECRUITING', 'startDateStruct': {'date': '2023-02-16', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-09', 'completionDateStruct': {'date': '2024-06', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2023-09-25', 'studyFirstSubmitDate': '2020-10-13', 'studyFirstSubmitQcDate': '2020-10-13', 'lastUpdatePostDateStruct': {'date': '2023-09-28', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-10-19', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-06', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Percentage of Perfused Small Vessel (PPV)', 'timeFrame': 'Daily assessment from day 0 to a maximum of 7 days', 'description': 'The absolute number of completely perfused small vessels (diameter \\< 20μm) divided by the absolute number of small vessels (diameter \\< 20μm).'}, {'measure': '28-days All-Cause Mortality', 'timeFrame': '28-days after enrollment'}], 'secondaryOutcomes': [{'measure': 'Perfused Small Vessel Density (PVD)', 'timeFrame': 'Daily assessment from day 0 to a maximum of 7 days', 'description': 'The percentage area occupied by the small vessels (diameter \\<20μm)'}, {'measure': 'Blood Flow Index (BFI)', 'timeFrame': 'Daily assessment from day 0 to a maximum of 7 days', 'description': 'The average flow signal'}, {'measure': 'Heterogeneity Index', 'timeFrame': 'Daily assessment from day 0 to a maximum of 7 days', 'description': 'The difference between the highest and the lowest BFI divided by the mean BFI'}, {'measure': 'ICU mortality', 'timeFrame': '90-days after enrollment'}, {'measure': 'Hospital mortality', 'timeFrame': '90-days after enrollment'}, {'measure': 'ICU length of stay', 'timeFrame': '90-days after enrollment'}, {'measure': 'Hospital length of stay', 'timeFrame': '90-days after enrollment'}, {'measure': 'Ventilator free-days', 'timeFrame': '90-days after enrollment'}, {'measure': 'Vasopressor free-days', 'timeFrame': '90-days after enrollment'}, {'measure': 'Renal replacement therapy free-days', 'timeFrame': '90-days after enrollment'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Septic Shock']}, 'referencesModule': {'references': [{'pmid': '30741328', 'type': 'BACKGROUND', 'citation': 'De Backer D, Cecconi M, Lipman J, Machado F, Myatra SN, Ostermann M, Perner A, Teboul JL, Vincent JL, Walley KR. Challenges in the management of septic shock: a narrative review. Intensive Care Med. 2019 Apr;45(4):420-433. doi: 10.1007/s00134-019-05544-x. Epub 2019 Feb 11.'}, {'pmid': '27660252', 'type': 'BACKGROUND', 'citation': 'Lipinska-Gediga M. Sepsis and septic shock-is a microcirculation a main player? Anaesthesiol Intensive Ther. 2016;48(4):261-265. doi: 10.5603/AIT.a2016.0037. Epub 2016 Sep 23.'}, {'pmid': '26729241', 'type': 'BACKGROUND', 'citation': 'Ince C. Hemodynamic coherence and the rationale for monitoring the microcirculation. Crit Care. 2015;19 Suppl 3(Suppl 3):S8. doi: 10.1186/cc14726. Epub 2015 Dec 18.'}, {'pmid': '26103150', 'type': 'BACKGROUND', 'citation': 'Ait-Oufella H, Bourcier S, Lehoux S, Guidet B. Microcirculatory disorders during septic shock. Curr Opin Crit Care. 2015 Aug;21(4):271-5. doi: 10.1097/MCC.0000000000000217.'}, {'pmid': '24758985', 'type': 'BACKGROUND', 'citation': 'Ince C. The rationale for microcirculatory guided fluid therapy. Curr Opin Crit Care. 2014 Jun;20(3):301-8. doi: 10.1097/MCC.0000000000000091.'}, {'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': '29229445', 'type': 'BACKGROUND', 'citation': 'Spaide RF, Fujimoto JG, Waheed NK, Sadda SR, Staurenghi G. Optical coherence tomography angiography. Prog Retin Eye Res. 2018 May;64:1-55. doi: 10.1016/j.preteyeres.2017.11.003. Epub 2017 Dec 8.'}, {'pmid': '30984909', 'type': 'BACKGROUND', 'citation': 'Onishi AC, Fawzi AA. An overview of optical coherence tomography angiography and the posterior pole. Ther Adv Ophthalmol. 2019 Apr 3;11:2515841419840249. doi: 10.1177/2515841419840249. eCollection 2019 Jan-Dec.'}, {'pmid': '28579550', 'type': 'BACKGROUND', 'citation': 'Sambhav K, Grover S, Chalam KV. The application of optical coherence tomography angiography in retinal diseases. Surv Ophthalmol. 2017 Nov-Dec;62(6):838-866. doi: 10.1016/j.survophthal.2017.05.006. Epub 2017 Jun 1.'}, {'pmid': '29843760', 'type': 'BACKGROUND', 'citation': 'Alnawaiseh M, Ertmer C, Seidel L, Arnemann PH, Lahme L, Kampmeier TG, Rehberg SW, Heiduschka P, Eter N, Hessler M. Feasibility of optical coherence tomography angiography to assess changes in retinal microcirculation in ovine haemorrhagic shock. Crit Care. 2018 May 29;22(1):138. doi: 10.1186/s13054-018-2056-3.'}, {'pmid': '28395665', 'type': 'BACKGROUND', 'citation': 'Erikson K, Liisanantti JH, Hautala N, Koskenkari J, Kamakura R, Herzig KH, Syrjala H, Ala-Kokko TI. Retinal arterial blood flow and retinal changes in patients with sepsis: preliminary study using fluorescein angiography. Crit Care. 2017 Apr 10;21(1):86. doi: 10.1186/s13054-017-1676-3.'}, {'pmid': '12091178', 'type': 'BACKGROUND', 'citation': 'De Backer D, Creteur J, Preiser JC, Dubois MJ, Vincent JL. Microvascular blood flow is altered in patients with sepsis. Am J Respir Crit Care Med. 2002 Jul 1;166(1):98-104. doi: 10.1164/rccm.200109-016oc.'}, {'pmid': '15343008', 'type': 'BACKGROUND', 'citation': 'Sakr Y, Dubois MJ, De Backer D, Creteur J, Vincent JL. Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock. Crit Care Med. 2004 Sep;32(9):1825-31. doi: 10.1097/01.ccm.0000138558.16257.3f.'}, {'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.'}, {'pmid': '25928214', 'type': 'BACKGROUND', 'citation': 'Povoa P, Salluh JI, Martinez ML, Guillamat-Prats R, Gallup D, Al-Khalidi HR, Thompson BT, Ranieri VM, Artigas A. Clinical impact of stress dose steroids in patients with septic shock: insights from the PROWESS-Shock trial. Crit Care. 2015 Apr 28;19(1):193. doi: 10.1186/s13054-015-0921-x.'}]}, 'descriptionModule': {'briefSummary': 'Purpose and rationale: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis and septic shock are major public health problems killing one in every three patients. Microcirculatory dysfunction is frequent in septic shock. The duration and severity of this dysfunction have a prognostic impact by being associated with organ failure and mortality. Our study purposes to demonstrate the feasibility of optical coherence tomography angiography (OCTA) to improve assessment of microcirculatory dysfunction by showing that retinal and choroidal microcirculatory changes with prognostic impact are present during septic shock.\n\nPrimary objective: To characterize the alterations of retinal and choroidal microcirculation in septic shock.\n\nWe will test the hypothesis that retinal and/or choroidal microcirculation shows dysfunctional changes (lower vascular density, lower percentage of perfused small vessel, lower blood flow index and higher vascular heterogeneity) in septic shock patients.\n\nSecondary objective: To test the prognostic value of retinal and choroidal microcirculatory dysfunction in septic shock.\n\nWe will test the hypothesis that higher magnitude and persistence of retinal and/or choroidal microcirculatory dysfunction beyond the successful macro-hemodynamic resuscitation are independent predictors of organ failure and mortality in septic shock patients.\n\nStudy type: Two sequential observational studies.\n\nStudy design: A cross-sectional case-control study followed by a prospective cohort study with a 90-days longitudinal follow-up period.\n\nStudy population: 165 septic shock patients and 30 healthy controls.\n\nStudy duration: 90 days from enrolment to final follow-up assessment. One to two years of enrolment.', 'detailedDescription': 'Purpose and rationale: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis and septic shock are major public health problems killing one in every three patients. Microcirculatory dysfunction is frequent in septic shock. The duration and severity of this dysfunction have a prognostic impact by being associated with organ failure and mortality. Our study purposes to demonstrate the feasibility of OCTA to improve assessment of microcirculatory dysfunction by showing that retinal and choroidal microcirculatory changes with prognostic impact are present during septic shock.\n\nPrimary objective (specific aim 1): To characterize the alterations of retinal and choroidal microcirculation in septic shock.\n\nWe will test the hypothesis that retinal and/or choroidal microcirculation shows dysfunctional changes (lower vascular density, lower percentage of perfused small vessel, lower blood flow index and higher vascular heterogeneity) in septic shock patients.\n\nSecondary objective (specific aim 2): To test the prognostic value of retinal and choroidal microcirculatory dysfunction in septic shock.\n\nWe will test the hypothesis that higher magnitude and persistence of retinal and/or choroidal microcirculatory dysfunction beyond the successful macro-hemodynamic resuscitation are independent predictors of organ failure and mortality in septic shock patients.\n\nStudy type: Two sequential observational studies.\n\nStudy design: A cross-sectional case-control study followed by a prospective cohort study with a 90-days longitudinal follow-up period.\n\nStudy population: 165 septic shock patients and 30 healthy controls. Power and sample size calculations: Based on sublingual percentage of perfused small vessel (PPV) difference previously reported between septic shock patients and healthy controls (60% vs. 95%), we estimate that we will need to enrol 27 patients and 27 controls to demonstrate the same difference at the retina and choroid. To show a PPV difference between survivors and non-survivors (70% vs. 46%) in the septic shock group, also based on previous reports at the sublingual microcirculatory level, we estimate that we will need to enrol 150 septic shock patients. These calculations assumed an alpha level of 0.05 and a power of 80%. Our Department admits about 200 septic shock patients annually, so to account for drop-outs and limitations with enrolment (10-20% refusal to participate) we decided to increase our enrolment goal by 10% to 165 septic shock patients and 30 healthy controls.\n\nRecruitment and inform consent: Recruitment will take place at the Intensive Care Medicine Department of Hospital da Luz Lisboa. Patients admitted to the Department with the diagnosis of septic shock will be screened for eligibility. If the patients are eligible to participate, they will be invited to enrol in the study by the principal investigator or other ICU medical team member. The study objectives and procedures will be explained to them. If the patient agrees to participate in the study, a written informed consent will be sign before enrolment. If the patient is unable to give informed consent to participate in the study, it will be asked to the reference next of kin using the same procedures as described before.\n\nStudy duration: 90 days from enrolment to final follow-up assessment. One to two years of enrolment.\n\nStudy procedures:\n\nBaseline Assessment: After confirmation of eligibility and enrolment in the studies, demographic data (age, gender), type of admission (urgent/elective, medical/surgical/trauma), patient origin (emergency department, ward, operation room), source of infection (lung, urinary tract, intra-abdominal, skin and soft tissues, others), prognostic scores (APACHE II, SAPS II) and organic dysfunction scores (SOFA, quick SOFA) will be collected at baseline for septic shock patients.\n\nStudy Assessments:\n\nOCTA: OCTA examination will be performed daily to septic shock patients from day 1 (less than 24 hours after diagnosis) until successful shock resolution (weaning from vasopressors) or until a maximum of 7 days. The healthy controls will be submitted to a single OCTA evaluation. We will use the Cirrus 6000® OCTA system (ZEISS, Germany) and the interpretation of OCTA images will be performed by two independent specialized ophthalmologists blinded to the clinical condition of patients. Images will be stored at the device working station.\n\nHemodynamic assessment: Every septic shock patient will have a central venous catheter and an arterial line in place according to the standard of care. Daily, during or within a maximum of 1 hour of OCTA examination, we will record the values of temperature, heart rate, mean arterial pressure, capillary refill time, central venous pressure, cardiac index, pH, PaCO2, PaO2, PvCO2, SaO2, SvO2, haemoglobin, serum lactate, fluid balance, oxygen delivery, oxygen consumption and oxygen extraction ratio.\n\nVasoactive and sedo-analgesic drugs: Daily we will record the vasoactive and sedo-analgesic drugs administered to septic shock patients and its total daily dose until complete weaning (defined as 24 hours free of vasopressors). Daily vasopressor score will also be calculated as suggested by Póvoa, P. et al.\n\nVentilatory and renal replacement therapy support: Daily we will record the type of ventilatory support (oxygen therapy, high flow oxygen therapy, non-invasive ventilation, invasive ventilation) and of renal replacement therapy (continuous, sustained low-efficiency, intermittent) used, if needed, until complete weaning.\n\nData analysis: In both studies, we will perform a descriptive statistical analysis of studied variables. Comparisons between healthy controls (single OCTA) and septic shock patients (first OCTA) to address endpoints related to specific aim 1 will be performed using t-Student test or Mann-Whitney test as appropriate. To address endpoints related to specific aim 2, we will compare survivors to non-survivors by doing a survival analysis using Kaplan-Meyer curves and Cox proportional hazards multivariable regression with microcirculatory measures as predictors. Additional comparisons will be performed using χ2 test, t-Student test, Mann-Whitney test and logistic regression as appropriate. We will assess confounding by adding significant variables in the regression models. We intend to perform a prespecified subgroup analysis of septic shock patients by serum lactate \\<4mmol/L vs. ≥4mmol/L and \\<2mmol/L vs. ≥2mmol/L. The correlation between retinal and choroidal microcirculation variables and macrohemodynamic variables will be assessed by the Spearman rank correlation coefficient. Area under Receiver Operating Characteristic curve of OCTA for prognostic outcomes will be calculated. A p-value \\< 0.05 will be considered statistically significant. Statistical analysis will be performed with STATA® 15 (StataCorp, Texas, USA).'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Source population:\n\n1. Cross-sectional case-control study: we intend to enrol 30 septic shock patients and 30 healthy controls.\n2. Prospective cohort study: we intend to enrol 165 septic shock patients (the first 30 patients will be the same from the cross-sectional case-control study).\n\nThe enrolment will take place from patients admitted to the Intensive Care Medicine Department of Hospital da Luz Lisboa, from February 2021 to February 2022. The healthy controls will be enrolled from our hospital staff.', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* ≥ 18 years-old\n* septic shock diagnosis (defined by the presence of sepsis according to Sepsis-3 definition plus a SOFA score ≥ 3 points at cardiovascular system despite adequate volume resuscitation) less than 24 hours before the first OCTA assessment\n\nExclusion Criteria:\n\n* Inability or willingness to provide informed consent from the patient or next of kin\n* Shock due to any other cause without septic shock\n* Bilateral eye absence\n* Previously known retinopathy\n* Previous retinal surgery or photocoagulation\n* Pregnant women\n* Participants with psychiatry disorders'}, 'identificationModule': {'nctId': 'NCT04593212', 'acronym': 'SshOCTA', 'briefTitle': 'Assessment of Microcirculatory Dysfunction in Septic Shock Patients by OCTA', 'organization': {'class': 'OTHER', 'fullName': 'Hospital da Luz, Portugal'}, 'officialTitle': 'Improving the Assessment of Microcirculatory Dysfunction in Septic Shock Patients Using Optical Coherence Tomography Angiography at the Bedside', 'orgStudyIdInfo': {'id': 'id.215'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Septic Shock Survivors', 'interventionNames': ['Diagnostic Test: Optical Coherence Tomography Angiography']}, {'label': 'Septic Shock Non-Survivors', 'interventionNames': ['Diagnostic Test: Optical Coherence Tomography Angiography']}], 'interventions': [{'name': 'Optical Coherence Tomography Angiography', 'type': 'DIAGNOSTIC_TEST', 'description': 'Evaluation of microcirculatory dysfunction by assessment of retinal and choroidal microvasculature with optical coherence tomography angiography (OCTA)', 'armGroupLabels': ['Septic Shock Non-Survivors', 'Septic Shock Survivors']}]}, 'contactsLocationsModule': {'locations': [{'zip': '1500-060', 'city': 'Lisbon', 'status': 'RECRUITING', 'country': 'Portugal', 'contacts': [{'name': 'André Alexandre, MD', 'role': 'CONTACT', 'email': 'andre.alexandre@hospitaldaluz.pt', 'phone': '351217104400'}], 'facility': 'Hospital da Luz Lisboa', 'geoPoint': {'lat': 38.72509, 'lon': -9.1498}}], 'centralContacts': [{'name': 'André Alexandre, MD', 'role': 'CONTACT', 'email': 'andre.alexandre@hospitaldaluz.pt', 'phone': '351217104400'}], 'overallOfficials': [{'name': 'André Alexandre, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': '11170'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Hospital da Luz, Portugal', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}