COVID-19 Acute Respiratory Distress SyndromeCA-COVIDNCT04930874
Cerebral Autoregulation and COVID-19
A study testing NIRS (Near-Infrared Spectroscopy) in people with COVID-19 Acute Respiratory Distress Syndrome and COVID-19 Pneumonia, run by University of Athens at 1 site in Greece.
Trial summary
This study aims to assess cerebral autoregulation by near-infrared spectroscopy (NIRS) in patients with severe coronavirus disease 19 (COVID-19). Results on COVID-19 participants will be compared with prior results of patients with septic shock and cardiac arrest, who participated in NCT03649633 and NCT02790788… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19 Acute Respiratory Distress Syndrome, COVID-19 Pneumonia
- What is being tested?
- NIRS (Near-Infrared Spectroscopy)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteGreece
- Study dates
- 22 Jun 2021to 16 Sep 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Admission to ICU and endotracheal intubation/mechanical ventilation for severe COVID-19 infection
Who cannot join
- Age <18 years
- Pregnancy
- Patients with a terminal underlying disease who are unlikely to survive until discharge from the hospital
- Patients with acquired immunodeficiency and ("pre-COVID") lymphocyte Cluster Differentiation 4+ count <50 / μL
- Patients with COVID-19 who have been transferred from another hospital
- Patients with a history of allergic reaction
- Use of prone position to facilitate mechanical ventilation
- Absence of signed informed consent from a first degree relative
Trial locations and contacts
1 site in 1 country.
Greece1 site
Department of Intensive Care Medicine Evaggelismos General Hospital
Athens, Attica, 10675
About this study
Official title: Cerebral Autoregulation and Severe Coronavirus Disease 19 [CA-COVID]: a Single-center Physiological Study
This study aims to assess cerebral autoregulation by near-infrared spectroscopy (NIRS) in patients with severe coronavirus disease 19 (COVID-19). Results on COVID-19 participants will be compared with prior results of patients with septic shock and cardiac arrest, who participated in NCT03649633 and NCT02790788, respectively.
Read the detailed description
Background and Rationale:
Septic encephalopathy is a serious complication of sepsis / septic shock. In postmortem, human brain samples, two forms of neuraxonal injury have been described, namely, scattered ischemic lesions and diffuse injury. Prior evidence suggests that cerebral autoregulation is impaired in patients with septic shock, and this may render the central nervous system more vulnerable to direct ischemic damage, especially during episodes of hypotension. Recent observational data suggest that impaired cerebral autoregulation is associated with death within 3 months in patients with septic shock. Near-infrared spectroscopy (NIRS) constitutes an established method of noninvasive assessment of cerebral autoregulation and also provides the capability of semiquantitative assessment of regional cerebral blood flow. Severe coronavirus disease (COVID-19) is characterized by hypoxemia due to pneumonia, thromboembolic events that often affect the cerebral and pulmonary vascular network, vasodilatory shock and multiorgan failure. Pathophysiological mechanisms have features in common with those of septic shock and include "cytokine storm", diffuse vascular endothelial involvement, micro- and macro-vascular thrombosis and dysregulation of micro-circulation and vascular tone. In the present study, the following 3 hypotheses will be tested: 1. Cerebral autoregulation is likely to be severely impaired or even abolished in patients with COVID-19 who require admission to an Intensive Care Unit (ICU). In addition, the correlation between the NIRS Tissue Oxygenation Index and the mean arterial pressure may be stronger in COVID-19 compared to septic shock and comparable to that determined after cardiac arrest. 2. Cerebral autoregulation is likely to be associated with known COVID-19 severity markers such as lymphopenia and elevated C-reactive protein (CRP), ferritin, delta dimers (D-dimers) and lactate dehydrogenase (LDH) 3. The early (ie on ICU days 1 and 3) absence of cerebral autoregulation is likely to be associated with residual neurological deficits.
METHODS:
NIRS monitoring will be performed for approximately 90 minutes at 2 mean blood pressure levels (MAP, i.e. 65-70 mmHg and 95-100 mmHg) within 12-48 hours and 60-84 hours after admission to the ICU for severe COVID-19 infection. Autoregulation will be assessed using Tissue Oxygenation Index values and mean arterial pressure (MAP) values in a regression analysis and will be considered sufficient if the relative Pearson correlation coefficient is less than 0.3 Cerebral blood flow will be assessed by blood flow index (BFI) determination after intravenous infusion of 5 mg indocyanine.
ICU Protocol: All COVID-19 patients participating in this study will be treated in a standardized manner that includes: An intermediate dose of Enoxaparin, e.g. 4000 units x 2 subcutaneously 2. Treatment with remdesivir and dexamethasone 3. Up to 2 broad-spectrum antibiotics to treat possibly co-existing bacterial respiratory tract infection 4. A conservative fluid management strategy 5. A protective ventilation strategy in a semirecumbent position 5. Anesthesia with Midazolam, Propofol and Remifentanil 7. Enteral nutrition that will start within 24 hours after admission to the ICU, 8. Permissive hyperglycemia (blood glucose 150-200 mg / dL).
Data Collection and Patient Monitoring:
Monitoring of patients during the first 10 days after inclusion in the study will include 1) Determination and recording of hemodynamic parameters and hemodynamic support, blood gases and arterial blood lactate at 9 p.m. 2) Blood sampling at 24-48, 72 hours and 7 days after inclusion in the study for determination of serum cytokines and 3) Daily recording of laboratory values, fluid balance and administration. The results of 2-4 daily determinations of blood glucose will be recorded and then the incidence of hyperglycemia (defined as blood glucose in excess of 200 mg) will be analyzed. Follow-up until day 60 after inclusion in the study will include organic failures and the number of days without mechanical ventilatory assistance. Finally, the length of stay in the ICU, the date of discharge from the hospital and the morbidity and complications throughout the patient's treatment until discharge from the hospital will be recorded.
Predefined comparisons: The severity of cerebral autoregulation disturbance in patients with COVID-19 will be compared with the cerebral autoregulation disturbance in 1) patients with septic shock (n = 32, NCT03649633, www.clinicaltrials.gov) and 2) cardiac arrest (n = 30, NCT02790788, www.clinicaltrials.gov). Also, other -pre-specified -by the respective research protocols- patient monitoring variables will be compared between the aforementioned groups of patients.
Names / degrees of Associates:
Alexandros Kouvarakos, Physiotherapist; Eirini Patsaki, Physiotherapist; Sotirios Malachias, MD, PhD; Charikleia Vrettou, MD, PhD; Stylianos Kokkoris, MD, PhD; Prodromos Temperikidis, MD, PhD; Aggeliki Kannavou, MD, PhD; George Adamos, MD, PhD
- Being tested
- NIRS (Near-Infrared Spectroscopy)
- Keywords
- COVID-19, Cerebrovascular circulation, Spectroscopy, Near-Infrared
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NIRS (Near-Infrared Spectroscopy)Other
NIRS assessment of cerebral autoregulation and cerebral blood flow
| Study group | Role | What they receive |
|---|---|---|
| ICU patients with COVID-19 | Experimental | NIRS monitoring will be performed for approximately 90 minutes at 2 mean blood pressure levels (MAP, ie 65-70 mmHg and 95-100 mmHg) within 12-48 hours and 60-84 hours after admission to the ICU for severe COVID-19 infection. Autoregulation will be assessed using Tissue Oxygenation Index values and mean arterial pressure values in a regression analysis and will be considered sufficient if the relative Pearson correlation coefficient is less than 0.3. Cerebral blood flow will be assessed by blood flow index determination after intravenous infusion of 5 mg indocyanine. Receives: Other: NIRS (Near-Infrared Spectroscopy) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cerebral autoregulation
The tissue oxygenation index of the frontal cortex will be determined (at a rate of 180 measurements / min) while increasing MAP from a minimum of 65-75 mmHg to a maximum of 90-100 mmHg by changing the vasopressor infusion rate. Cooncurrent changes in MAP will also be recorded. Subsequently, linear regression between MAP and the Tissue Oxygenation Index will be performed. A Pearson correlation coefficient of >0.3 will be considered as "absence" of autoregulation of the cerebral vasculature.
Measured: Days 1-4 of ICU admission
Cerebral blood flow
Cerebral blood flow at MAP 65-75 mmHg and MAP 90-100 mmHg by determination of the blood flow index.
Measured: Days 1-4 of ICU admission
Secondary outcomes (6)
Neurologic failure free days
Days without neurologic failure throughout the 60-day follow-up period. Patients with a Glasgow Coma Scale of <9 will be considered to have neurological failure.
Measured: Days 1-60 after ICU admission
Ventilator free days
Days without mechanical ventilatory assistance throughout the 60-day follow-up period. On any given day of follow-up, patients will be considered as "ventilator-free" only if there is no need for respiratory support within the preceding 24 hours.
Measured: Days 1-60 after ICU admission
Survival to hospital discharge and neurological outcome
Survival to hospital discharge and neurological outcome assessed by the Cerebral Performance Category Score, and the Modified Rankin Scale Score.
Measured: Days 1-60 after ICU admission
Survival to hospital discharge and neurological outcome
Survival to hospital discharge and neurological outcome assessed by the Cerebral Performance Category (CPC) Score. The CPC Score ranges from 1 to 5, with 1 corresponding to the best possible outcome (i.e. patient able to work and lead a normal life), and 5 corresponding to the worst possible outcome (i.e. brain death).
Measured: Days 1-60 after ICU admission
Survival to hospital discharge and neurological outcome
Survival to hospital discharge and neurological outcome assessed by the Modified Rankin Scale (mRS) Score. The mRS ranges from 0, corresponding to the best possible outcome (i.e. no symptoms related to a neurological deficit), to 6 corresponding to the worst possible outcome (i.e. death).
Measured: Days 1-60 after ICU admission
Serum Cytokines
Tumor Necrosis Factor alpha, Interleukin (IL)-1 beta, IL-6, IL-8, and IL-10 levels at 24-48, 72 hours and 7 days after enrollment. Plasma concentrations of all the aforementioned cytokines will be expressed in picograms per milliliter.
Measured: Days 1-7 after ICU admission
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2021
- Study start22 Jun 2021
- Primary completion16 Sep 2022
- Study completion16 Sep 2022
Why it stopped: Low rate of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for COVID-19 Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Athens
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Spyros D. Mentzelopoulos, University of Athens
- Investigators
- Spyros D Mentzelopoulos, MD, Professor, Principal investigator, National and Kapodistrian University of AthensAnastasia D Kotanidou, MD, Professor, Study chair, National and Kapodistrian University of Athens
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04930874
- Sponsor's protocol ID
- CA-COVID 196/10-6-2021
- Acronym
- CA-COVID
- Status last verified
- Dec 2024
- First submitted
- 15 Jun 2021
- Last updated
- 19 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ehler J, Barrett LK, Taylor V, Groves M, Scaravilli F, Wittstock M, Kolbaske S, Grossmann A, Henschel J, Gloger M, Sharshar T, Chretien F, Gray F, Noldge-Schomburg G, Singer M, Sauer M, Petzold A. Translational evidence for two distinct patterns of neuroaxonal injury in sepsis: a longitudinal, prospective translational study. Crit Care. 2017 Oct 23;21(1):262. doi: 10.1186/s13054-017-1850-7.
PubMed 29058589Taccone FS, Castanares-Zapatero D, Peres-Bota D, Vincent JL, Berre' J, Melot C. Cerebral autoregulation is influenced by carbon dioxide levels in patients with septic shock. Neurocrit Care. 2010 Feb;12(1):35-42. doi: 10.1007/s12028-009-9289-6.
PubMed 19806473Schramm P, Klein KU, Falkenberg L, Berres M, Closhen D, Werhahn KJ, David M, Werner C, Engelhard K. Impaired cerebrovascular autoregulation in patients with severe sepsis and sepsis-associated delirium. Crit Care. 2012 Oct 4;16(5):R181. doi: 10.1186/cc11665.
PubMed 23036135Bindra J, Pham P, Chuan A, Jaeger M, Aneman A. Is impaired cerebrovascular autoregulation associated with outcome in patients admitted to the ICU with early septic shock? Crit Care Resusc. 2016 Jun;18(2):95-101.
PubMed 27242107Donnelly J, Budohoski KP, Smielewski P, Czosnyka M. Regulation of the cerebral circulation: bedside assessment and clinical implications. Crit Care. 2016 May 5;20(1):129. doi: 10.1186/s13054-016-1293-6.
PubMed 27145751Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585.
PubMed 32031570Kaneko N, Satta S, Komuro Y, Muthukrishnan SD, Kakarla V, Guo L, An J, Elahi F, Kornblum HI, Liebeskind DS, Hsiai T, Hinman JD. Flow-Mediated Susceptibility and Molecular Response of Cerebral Endothelia to SARS-CoV-2 Infection. Stroke. 2021 Jan;52(1):260-270. doi: 10.1161/STROKEAHA.120.032764. Epub 2020 Nov 9.
PubMed 33161843Cagnazzo F, Piotin M, Escalard S, Maier B, Ribo M, Requena M, Pop R, Hasiu A, Gasparotti R, Mardighian D, Piano M, Cervo A, Eker OF, Durous V, Sourour NA, Elhorany M, Zini A, Simonetti L, Marcheselli S, Paolo NN, Houdart E, Guedon A, Ligot N, Mine B, Consoli A, Lapergue B, Cordona Portela P, Urra X, Rodriguez A, Bolognini F, Lebedinsky PA, Pasco-Papon A, Godard S, Marnat G, Sibon I, Limbucci N, Nencini P, Nappini S, Saia V, Caldiera V, Romano D, Frauenfelder G, Gallesio I, Gola G, Menozzi R, Genovese A, Terrana A, Giorgianni A, Cappellari M, Augelli R, Invernizzi P, Pavia M, Lafe E, Cavallini A, Giossi A, Besana M, Valvassori L, Macera A, Castellan L, Salsano G, Di Caterino F, Biondi A, Arquizan C, Lebreuche J, Galvano G, Cannella A, Cosottini M, Lazzarotti G, Guizzardi G, Stecco A, Tassi R, Bracco S, Bianchini E, Micieli C, Pascarella R, Napoli M, Causin F, Desal H, Cotton F, Costalat V; ET-COVID-19 Study Group*. European Multicenter Study of ET-COVID-19. Stroke. 2021 Jan;52(1):31-39. doi: 10.1161/STROKEAHA.120.031514. Epub 2020 Nov 23.
PubMed 33222617Alharthy A, Faqihi F, Papanikolaou J, Balhamar A, Blaivas M, Memish ZA, Karakitsos D. Thrombolysis in severe COVID-19 pneumonia with massive pulmonary embolism. Am J Emerg Med. 2021 Mar;41:261.e1-261.e3. doi: 10.1016/j.ajem.2020.07.068. Epub 2020 Jul 30.
PubMed 32763101Zangrillo A, Landoni G, Beretta L, Morselli F, Serpa Neto A, Bellomo R; COVID-BioB Study Group. Angiotensin II infusion in COVID-19-associated vasodilatory shock: a case series. Crit Care. 2020 May 15;24(1):227. doi: 10.1186/s13054-020-02928-0. No abstract available.
PubMed 32414393Dupont A, Rauch A, Staessens S, Moussa M, Rosa M, Corseaux D, Jeanpierre E, Goutay J, Caplan M, Varlet P, Lefevre G, Lassalle F, Bauters A, Faure K, Lambert M, Duhamel A, Labreuche J, Garrigue D, De Meyer SF, Staels B, Vincent F, Rousse N, Kipnis E, Lenting P, Poissy J, Susen S; Lille Covid Research Network (LICORNE). Vascular Endothelial Damage in the Pathogenesis of Organ Injury in Severe COVID-19. Arterioscler Thromb Vasc Biol. 2021 May 5;41(5):1760-1773. doi: 10.1161/ATVBAHA.120.315595. Epub 2021 Feb 25.
PubMed 33626910Ince C. The microcirculation is the motor of sepsis. Crit Care. 2005;9 Suppl 4(Suppl 4):S13-9. doi: 10.1186/cc3753. Epub 2005 Aug 25.
PubMed 16168069Donati A, Domizi R, Damiani E, Adrario E, Pelaia P, Ince C. From macrohemodynamic to the microcirculation. Crit Care Res Pract. 2013;2013:892710. doi: 10.1155/2013/892710. Epub 2013 Feb 27.
PubMed 23509621Salama C, Han J, Yau L, Reiss WG, Kramer B, Neidhart JD, Criner GJ, Kaplan-Lewis E, Baden R, Pandit L, Cameron ML, Garcia-Diaz J, Chavez V, Mekebeb-Reuter M, Lima de Menezes F, Shah R, Gonzalez-Lara MF, Assman B, Freedman J, Mohan SV. Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia. N Engl J Med. 2021 Jan 7;384(1):20-30. doi: 10.1056/NEJMoa2030340. Epub 2020 Dec 17.
PubMed 33332779Jamil S, Mark N, Carlos G, Cruz CSD, Gross JE, Pasnick S. Diagnosis and Management of COVID-19 Disease. Am J Respir Crit Care Med. 2020 May 15;201(10):P19-P20. doi: 10.1164/rccm.2020C1. No abstract available.
PubMed 32223716
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cerebral Autoregulation and Severe Coronavirus Disease 19 [CA-COVID]: a Single-center Physiological Study
- ClinicalTrials.gov ID
- NCT04930874
- Acronym / sponsor ID
- CA-COVID / CA-COVID 196/10-6-2021
- Keywords
- COVID-19, Cerebrovascular circulation, Spectroscopy, Near-Infrared
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low rate of enrollment
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University of AthensUniversity, hospital or other
- Study start
- 22 Jun 2021 (actual)
- Primary completion
- 16 Sep 2022 (actual)
- Study completion
- 16 Sep 2022 (actual)
- First posted
- 18 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to assess cerebral autoregulation by near-infrared spectroscopy (NIRS) in patients with severe coronavirus disease 19 (COVID-19). Results on COVID-19 participants will be compared with prior results of patients with septic shock and cardiac arrest, who participated in NCT03649633 and NCT02790788, respectively.
Detailed description
Background and Rationale:
Septic encephalopathy is a serious complication of sepsis / septic shock. In postmortem, human brain samples, two forms of neuraxonal injury have been described, namely, scattered ischemic lesions and diffuse injury. Prior evidence suggests that cerebral autoregulation is impaired in patients with septic shock, and this may render the central nervous system more vulnerable to direct ischemic damage, especially during episodes of hypotension. Recent observational data suggest that impaired cerebral autoregulation is associated with death within 3 months in patients with septic shock. Near-infrared spectroscopy (NIRS) constitutes an established method of noninvasive assessment of cerebral autoregulation and also provides the capability of semiquantitative assessment of regional cerebral blood flow. Severe coronavirus disease (COVID-19) is characterized by hypoxemia due to pneumonia, thromboembolic events that often affect the cerebral and pulmonary vascular network, vasodilatory shock and multiorgan failure. Pathophysiological mechanisms have features in common with those of septic shock and include "cytokine storm", diffuse vascular endothelial involvement, micro- and macro-vascular thrombosis and dysregulation of micro-circulation and vascular tone. In the present study, the following 3 hypotheses will be tested: 1. Cerebral autoregulation is likely to be severely impaired or even abolished in patients with COVID-19 who require admission to an Intensive Care Unit (ICU). In addition, the correlation between the NIRS Tissue Oxygenation Index and the mean arterial pressure may be stronger in COVID-19 compared to septic shock and comparable to that determined after cardiac arrest. 2. Cerebral autoregulation is likely to be associated with known COVID-19 severity markers such as lymphopenia and elevated C-reactive protein (CRP), ferritin, delta dimers (D-dimers) and lactate dehydrogenase (LDH) 3. The early (ie on ICU days 1 and 3) absence of cerebral autoregulation is likely to be associated with residual neurological deficits.
METHODS:
NIRS monitoring will be performed for approximately 90 minutes at 2 mean blood pressure levels (MAP, i.e. 65-70 mmHg and 95-100 mmHg) within 12-48 hours and 60-84 hours after admission to the ICU for severe COVID-19 infection. Autoregulation will be assessed using Tissue Oxygenation Index values and mean arterial pressure (MAP) values in a regression analysis and will be considered sufficient if the relative Pearson correlation coefficient is less than 0.3 Cerebral blood flow will be assessed by blood flow index (BFI) determination after intravenous infusion of 5 mg indocyanine.
ICU Protocol: All COVID-19 patients participating in this study will be treated in a standardized manner that includes: An intermediate dose of Enoxaparin, e.g. 4000 units x 2 subcutaneously 2. Treatment with remdesivir and dexamethasone 3. Up to 2 broad-spectrum antibiotics to treat possibly co-existing bacterial respiratory tract infection 4. A conservative fluid management strategy 5. A protective ventilation strategy in a semirecumbent position 5. Anesthesia with Midazolam, Propofol and Remifentanil 7. Enteral nutrition that will start within 24 hours after admission to the ICU, 8. Permissive hyperglycemia (blood glucose 150-200 mg / dL).
Data Collection and Patient Monitoring:
Monitoring of patients during the first 10 days after inclusion in the study will include 1) Determination and recording of hemodynamic parameters and hemodynamic support, blood gases and arterial blood lactate at 9 p.m. 2) Blood sampling at 24-48, 72 hours and 7 days after inclusion in the study for determination of serum cytokines and 3) Daily recording of laboratory values, fluid balance and administration. The results of 2-4 daily determinations of blood glucose will be recorded and then the incidence of hyperglycemia (defined as blood glucose in excess of 200 mg) will be analyzed. Follow-up until day 60 after inclusion in the study will include organic failures and the number of days without mechanical ventilatory assistance. Finally, the length of stay in the ICU, the date of discharge from the hospital and the morbidity and complications throughout the patient's treatment until discharge from the hospital will be recorded.
Predefined comparisons: The severity of cerebral autoregulation disturbance in patients with COVID-19 will be compared with the cerebral autoregulation disturbance in 1) patients with septic shock (n = 32, NCT03649633, www.clinicaltrials.gov) and 2) cardiac arrest (n = 30, NCT02790788, www.clinicaltrials.gov). Also, other -pre-specified -by the respective research protocols- patient monitoring variables will be compared between the aforementioned groups of patients.
Names / degrees of Associates:
Alexandros Kouvarakos, Physiotherapist; Eirini Patsaki, Physiotherapist; Sotirios Malachias, MD, PhD; Charikleia Vrettou, MD, PhD; Stylianos Kokkoris, MD, PhD; Prodromos Temperikidis, MD, PhD; Aggeliki Kannavou, MD, PhD; George Adamos, MD, PhD
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ICU patients with COVID-19 | Experimental | Other: NIRS (Near-Infrared Spectroscopy)NIRS monitoring will be performed for approximately 90 minutes at 2 mean blood pressure levels (MAP, ie 65-70 mmHg and 95-100 mmHg) within 12-48 hours and 60-84 hours after admission to the ICU for severe COVID-19 infection. Autoregulation will be assessed using Tissue Oxygenation Index values and mean arterial pressure values in a regression analysis and will be considered sufficient if the relative Pearson correlation coefficient is less than 0.3. Cerebral blood flow will be assessed by blood flow index determination after intravenous infusion of 5 mg indocyanine. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Admission to ICU and endotracheal intubation/mechanical ventilation for severe COVID-19 infection
Key exclusion criteria (8 listed)
- Age <18 years
- Pregnancy
- Patients with a terminal underlying disease who are unlikely to survive until discharge from the hospital
- Patients with acquired immunodeficiency and ("pre-COVID") lymphocyte Cluster Differentiation 4+ count <50 / μL
- Patients with COVID-19 who have been transferred from another hospital
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NIRS (Near-Infrared Spectroscopy)NIRS assessment of cerebral autoregulation and cerebral blood flow | Other | ICU patients with COVID-19 |
Primary outcome
Cerebral autoregulation
Time frame: Days 1-4 of ICU admission
The tissue oxygenation index of the frontal cortex will be determined (at a rate of 180 measurements / min) while increasing MAP from a minimum of 65-75 mmHg to a maximum of 90-100 mmHg by changing the vasopressor infusion rate. Cooncurrent changes in MAP will also be recorded. Subsequently, linear regression between MAP and the Tissue Oxygenation Index will be performed. A Pearson correlation coefficient of >0.3 will be considered as "absence" of autoregulation of the cerebral vasculature.
Cerebral blood flow
Time frame: Days 1-4 of ICU admission
Cerebral blood flow at MAP 65-75 mmHg and MAP 90-100 mmHg by determination of the blood flow index.
6 secondary outcomes
Neurologic failure free days
Time frame: Days 1-60 after ICU admission
Ventilator free days
Time frame: Days 1-60 after ICU admission
Survival to hospital discharge and neurological outcome
Time frame: Days 1-60 after ICU admission
Survival to hospital discharge and neurological outcome
Time frame: Days 1-60 after ICU admission
Survival to hospital discharge and neurological outcome
Time frame: Days 1-60 after ICU admission
Serum Cytokines
Time frame: Days 1-7 after ICU admission
Results and safety
The study was stopped early (reason given: Low rate of enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2024.
- Background: PubMed 29058589Ehler J, Barrett LK, Taylor V, Groves M, Scaravilli F, Wittstock M, Kolbaske S, Grossmann A, Henschel J, Gloger M, Sharshar T, Chretien F, Gray F, Noldge-Schomburg G, Singer M, Sauer M, Petzold A. Translational evidence for two distinct patterns of neuroaxonal injury in sepsis: a longitudinal, prospective translational study. Crit Care. 2017 Oct 23;21(1):262. doi: 10.1186/s13054-017-1850-7.
- Background: PubMed 19806473Taccone FS, Castanares-Zapatero D, Peres-Bota D, Vincent JL, Berre' J, Melot C. Cerebral autoregulation is influenced by carbon dioxide levels in patients with septic shock. Neurocrit Care. 2010 Feb;12(1):35-42. doi: 10.1007/s12028-009-9289-6.
- Background: PubMed 23036135Schramm P, Klein KU, Falkenberg L, Berres M, Closhen D, Werhahn KJ, David M, Werner C, Engelhard K. Impaired cerebrovascular autoregulation in patients with severe sepsis and sepsis-associated delirium. Crit Care. 2012 Oct 4;16(5):R181. doi: 10.1186/cc11665.
- Background: PubMed 27242107Bindra J, Pham P, Chuan A, Jaeger M, Aneman A. Is impaired cerebrovascular autoregulation associated with outcome in patients admitted to the ICU with early septic shock? Crit Care Resusc. 2016 Jun;18(2):95-101.
- Background: PubMed 27145751Donnelly J, Budohoski KP, Smielewski P, Czosnyka M. Regulation of the cerebral circulation: bedside assessment and clinical implications. Crit Care. 2016 May 5;20(1):129. doi: 10.1186/s13054-016-1293-6.
- Background: PubMed 32031570Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585.
- Background: PubMed 33161843Kaneko N, Satta S, Komuro Y, Muthukrishnan SD, Kakarla V, Guo L, An J, Elahi F, Kornblum HI, Liebeskind DS, Hsiai T, Hinman JD. Flow-Mediated Susceptibility and Molecular Response of Cerebral Endothelia to SARS-CoV-2 Infection. Stroke. 2021 Jan;52(1):260-270. doi: 10.1161/STROKEAHA.120.032764. Epub 2020 Nov 9.
- Background: PubMed 33222617Cagnazzo F, Piotin M, Escalard S, Maier B, Ribo M, Requena M, Pop R, Hasiu A, Gasparotti R, Mardighian D, Piano M, Cervo A, Eker OF, Durous V, Sourour NA, Elhorany M, Zini A, Simonetti L, Marcheselli S, Paolo NN, Houdart E, Guedon A, Ligot N, Mine B, Consoli A, Lapergue B, Cordona Portela P, Urra X, Rodriguez A, Bolognini F, Lebedinsky PA, Pasco-Papon A, Godard S, Marnat G, Sibon I, Limbucci N, Nencini P, Nappini S, Saia V, Caldiera V, Romano D, Frauenfelder G, Gallesio I, Gola G, Menozzi R, Genovese A, Terrana A, Giorgianni A, Cappellari M, Augelli R, Invernizzi P, Pavia M, Lafe E, Cavallini A, Giossi A, Besana M, Valvassori L, Macera A, Castellan L, Salsano G, Di Caterino F, Biondi A, Arquizan C, Lebreuche J, Galvano G, Cannella A, Cosottini M, Lazzarotti G, Guizzardi G, Stecco A, Tassi R, Bracco S, Bianchini E, Micieli C, Pascarella R, Napoli M, Causin F, Desal H, Cotton F, Costalat V; ET-COVID-19 Study Group*. European Multicenter Study of ET-COVID-19. Stroke. 2021 Jan;52(1):31-39. doi: 10.1161/STROKEAHA.120.031514. Epub 2020 Nov 23.
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- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Spyros D Mentzelopoulos, MD, Professor principal investigator
National and Kapodistrian University of Athens
Anastasia D Kotanidou, MD, Professor study chair
National and Kapodistrian University of Athens
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing NIRS (Near-Infrared Spectroscopy) in people with COVID-19 Acute Respiratory Distress Syndrome and COVID-19 Pneumonia, run by University of Athens at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Low rate of enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cerebral autoregulation (time frame: Days 1-4 of ICU admission). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04930874, which also lists 17 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2024.