Intracranial PressureNCT04861402
Non-Invasive Intracranial Pressure in COVID-19 Individuals
An observational study of Intracranial Pressure, run by Federal University of São Paulo at 1 site in Brazil.
Trial summary
The use of non-invasive intracranial pressure monitoring, including intracranial pressure pulse morphology in patients with COVID-19, could calculate possible components associated with the presence of neurological symptoms in these patients, in addition to being a tool with the potential to monitor the repercussion… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Intracranial Pressure
- What is being tested?
- The ICP monitoring will be performed in a non-invasive method developed by Brain4Care
- Type of treatment
- Medical device
- How many people
- 60 participants
- Where
- 1 siteBrazil
- Study dates
- 30 Apr 2020to 15 Dec 2021
- Phase
- Observational
- 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
- Healthy volunteers accepted
- Adult, Older adult
Study population: This is a multicenter longitudinal study of 4 centers in Brazil: Hospital of São Paulo (Federal University of São Paulo), Benemérita Portuguese Charity Association, São Paulo-SP, ESHO Hospital Services Company AS, São Paulo, SP and Federal University of São Carlos, São Carlos-SP, from June to December of 2020. This will follow Helsinki recommendations for human protocols. This study was approved by Federal University of São Paulo's Human Research Ethics Committee (process number 4,050,985). The patients who completed the inclusion criteria (table 1) will be invited to participate, and they will receive an Informed Consent Form (ICF). At least 60 subjects will be included, and they will be equally divided into 4 groups.
Who may be able to join
- For COVID-19 group:
- Men and women (not pregnant) Older than 18 years old Diagnosis of COVID-19 confirmed by Reverse Transcription Polymerase Chain Reaction (RT-PCR) Subjects intubated or non-intubated Time between admission and study inclusion ≤ 72h For intubated group time between IUC admission and study inclusion ≤ 72h Time between onset symptoms and study inclusion ≤ 14 days No neurological acute disease No cutaneous injury in the head to impossibility the ICP monitoring ICF signed by the participant or his/her legal representative*
- No cutaneous injury in the head to impossibility the monitoring with the transcranial doppler helmet Patients who have not been submitted to decompressive craniectomy previously. Subjects intubated or non-intubated For intubated group time between IUC admission and study inclusion ≤ 72h Time between admission and study inclusion ≤ 72h Time between onset symptoms and study inclusion ≤14 days No neurological acute disease
- For Controls Group:
- Men and women (not pregnant) Older than 18 years old No cutaneous injury in the head to impossibility the ICP monitoring • For intubated group: ICF signed by the participant or his/her legal representative Intubated patients for others causes than COVID-19 or neurological diseases IUC admission and study inclusion ≤ 72h No symptoms of COVID-19 on the last 15 days
- For healthy group: No previous neurological disease No chronic disease as Diabetes Mellitus Type 2, Chronic Obstructive Pulmonary Disease (COPD), Heart Failure, hypertension or Chronic Kidney Disease (CKD)
- No cutaneous injury in the head to impossibility the monitoring with the transcranial doppler helmet Patients who have not been submitted to decompressive craniectomy previously.
- IUC admission and study inclusion ≤ 72h No neurological diseases
Who cannot join
- It will be excluded those who asked to stop their participation, and those with problems in acquiring ICP data.
Trial locations and contacts
1 site in 1 country.
About this study
The use of non-invasive intracranial pressure monitoring, including intracranial pressure pulse morphology in patients with COVID-19, could calculate possible components associated with the presence of neurological symptoms in these patients, in addition to being a tool with the potential to monitor the repercussion of MV at cerebral compliance patient patients. In addition, it is likely that patients with COVID-19 also have cerebral embolization more frequently than healthy patients, which is justified by transcranial doppler ultrasound assessment. The aim of the study is to monitor this brain pressure using a non-invasive method of monitoring, with a helmet-like system in place, for 1 hour for 7 consecutive days. There will be no associated invasive procedure of any kind. Monitoring will be done by the criteria themselves, no place where the patient and the mandatory volunteer. Another objective is to capture signs of microembolisms (small strokes that have not yet manifested) by performing a doppler ultrasound on the head with a helmet also for 1 hour, in a single evaluation.
The study population will include inpatients with COVID-19 infection. The control group will be in patients who do not have Covid-19. The control group will consist of people with similar characteristics and who have not recovered. Patients who meet the inclusion criteria incorporated into the monitoring with a non-invasive intracranial pressure device for 1 hour during hospitalization (Brain4Care® device approved by ANVISA), being monitored for up to seven days, in addition to monitoring for 1 hour with a transcranial doppler ultrasound helmet DWL® in a single assessment. There will be no invasive procedures or other equipment used without due knowledge by Organs competent bodies. It does not collect collection or retention of any biological material.
Read the detailed description
INTRODUCTION: The Coronavirus Disease 2019 (COVID-19) is an infectious disease transmitted one person to another mainly from cough and sneeze aerosols as well as from contaminated surfaces. The most common respiratory symptoms are dry cough, fever, and dyspnea, but the Severe Respiratory Acute Syndrome (SARS) can be installed increasing disease´s mortality. In addition, neurological symptoms have been described according the increase of severity and age. Changes of intracranial pressure (ICP) can partially explain the Central Nervous System (CNS) impairment due to COVID-19. The ICP waveform can bring relevant information about intracranial compliance, and, nowadays, it can be measured by non-invasive technology. Clinically, non-invasive ICP waveform assessment would help to understand the repercussion of Invasive Mechanical Ventilation (IMV) on CNS in COVID-19 persons. AIMS: This study aims to evaluate the ICP waveform in intubated and non-intubated COVID-19 persons. Furthermore, the association between ICP and IMV parameters, level of sedation, heart rate variability, neurological symptoms, neuroimage, and final discharge will be investigated. . METHODS: At least 30 COVID-19 individuals will be included within 72h from admission and 14 days from symptoms onset. They will be divided into two groups: non-intubated (n=15) and intubated, paired with non-COVID-19 ones (non-intubated and intubated non-COVID-19 groups, respectively). The non-invasive ICP monitoring will be daily performed for 7 consecutive days. The Brain4Care's device and Analytic System will be used to assess the three pulse peaks (P1, 2 and 3) at the ICP waveform. The following variables will be investigated: P1 and P2 amplitude, P2/P1 ratio, time to peak and time percentage of P2 higher than P1. For statistics, all variables will be tested as to their normal or non-normal distribution through appropriate statical analyzes. For basic demographic and clinical variables, descriptive data analysis will be used. The repetitive measurement Anova will be used for ICP outcomes throughout the days. Pearson's or Spearman´s correlations will be applied according to data distribution.
- Conditions
- Intracranial Pressure
- Being tested
- The ICP monitoring will be performed in a non-invasive method developed by Brain4Care
- Keywords
- Neurocritical care, Infectious Disease Medicine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
The ICP monitoring will be performed in a non-invasive method developed by Brain4CareDevice
Also called The presence of spontaneous microembolization will be assessed by means of non-invasive monitoring by transcranial doppler
The ICP monitoring will be performed in a non-invasive way through the cranial deformation method developed by Brain4Care Inc.
The selected patients will be monitored until 1h/day for 7 sequential days or even discharge. The clinical outcomes such as ventilatory status will be noted (if the subject is under oxygen supplementation, using non-invasive mechanical ventilation or intubated), the ventilatory parameters during the monitorization will be analyzed in the intubated group (or those from a non-intubated group who was intubated during the seven days of hospitalization) including IFO2, CV, PEEP, driving pressure, and pressure plate as well as ventilatory asynchronies. Some changes in ventilatory parameters during monitorization will be noted. These procedures will be applied to all groups, excepted to the healthy group. This last group will be monitored only once for 30 minutes at the Federal University of São Carlos (UFSCar).
| Study group | Role | What they receive |
|---|---|---|
| Non-intubated COVID-19 group | Men and women (not pregnant) Older than 18 years old Diagnosis of COVID-19 confirmed by Reverse Transcription Polymerase Chain Reaction (RT-PCR) Subjects intubated Time between admission and study inclusion ≤ 72h Non-intubated during the monitoring carried out in the study Time between onset symptoms and study inclusion ≤ 14 days No neurological acute disease No cutaneous injury in the head to impossibility the ICP monitoring No cutaneous injury in the head to impossibility the monitoring with the transcranial doppler helmet Patients who have not been submitted to decompressive craniectomy previously. Receives: Device: The ICP monitoring will be performed in a non-invasive method developed by Brain4Care | |
| Intubated COVID-19 group | Men and women (not pregnant) Older than 18 years old Diagnosis of COVID-19 confirmed by Reverse Transcription Polymerase Chain Reaction (RT-PCR) Subjects intubated Time between admission and study inclusion ≤ 72h For intubated group time between IUC admission and study inclusion ≤ 72h Time between onset symptoms and study inclusion ≤ 14 days No neurological acute disease No cutaneous injury in the head to impossibility the ICP monitoring No cutaneous injury in the head to impossibility the monitoring with the transcranial doppler helmet Patients who have not been submitted to decompressive craniectomy previously. Receives: Device: The ICP monitoring will be performed in a non-invasive method developed by Brain4Care | |
| Health control group | Men and women (not pregnant) Older than 18 years old No cutaneous injury in the head to impossibility the ICP monitoring No symptoms of COVID-19 on the last 15 days
• For healthy group: No previous neurological disease No chronic disease as Diabetes Mellitus Type 2, Chronic Obstructive Pulmonary Disease (COPD), Heart Failure, hypertension or Chronic Kidney Disease (CKD) No cutaneous injury in the head to impossibility the monitoring with the transcranial doppler helmet Patients who have not been submitted to decompressive craniectomy previously. Receives: Device: The ICP monitoring will be performed in a non-invasive method developed by Brain4Care | |
| Non-COVID-19 and non-neurological disease intubated group | Men and women (not pregnant) Older than 18 years old No cutaneous injury in the head to impossibility the ICP monitoring
• For intubated group: ICF signed by the participant or his/her legal representative* Intubated patients for others causes than COVID-19 or neurological diseases IUC admission and study inclusion ≤ 72h No symptoms of COVID-19 on the last 15 days No cutaneous injury in the head to impossibility the monitoring with the transcranial doppler helmet Patients who have not been submitted to decompressive craniectomy previously. Receives: Device: The ICP monitoring will be performed in a non-invasive method developed by Brain4Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
ICP pulse waveform
To evaluate the ICP pulse waveform in patients with COVID-19 non-intubated compared to healthy subjects.
Measured: 01/06/2021
ICP pulse waveform 2
To evaluate the ICP pulse waveform in intubated patients with COVID-19 compared to intubated subjects with other diagnoses except COVID-19.
Measured: 01/06/2021
spontaneous microemboli
To evaluate the spontaneous microemboli presence with TCD in those subjects who received the ICP monitoring.
Measured: 01/06/2021
Secondary outcomes (12)
Secondary Outcome
To correlate the ICP pulse waveform and the presence of neurological symptoms on hospital admission in the non-intubated COVID-19 group
Measured: 01/06/21
Secondary Outcome 1
To correlate the ICP pulse waveform and the emergence of neurological symptoms during the admission in the non-intubated COVID-19 group
Measured: 01/06/2021
Secondary Outcome 2
To correlate the ICP pulse waveform and the necessity of intubation during hospitalization time in the non-intubated COVID-19 group
Measured: 01/06/2021
Secondary Outcome 3
To correlate the ICP pulse waveform and the Heart Rate Variability in the non-intubated COVID-19 group
Measured: 01/06/2021
Secondary Outcome 4
To correlate the ICP pulse waveform and neuroimaging when available in the non-intubated COVID-19 group
Measured: 01/06/2021
Secondary Outcome 5
To correlate the ICP pulse waveform and the outcome on discharge in the non-intubated COVID-19 group
Measured: 01/06/2021
Secondary Outcome 6
To correlate the ICP pulse waveform to ventilatory parameters (inspired fraction of oxygen [IFO2], PEEP, Current Volum [CV] and driving pressure) in the intubated COVID-19 group
Measured: 01/06/2021
Secondary Outcome 7
To correlate the ICP pulse waveform to sedation used in the intubated COVID-19 group
Measured: 01/06/2021
Secondary Outcome 8
To correlate the ICP pulse waveform to HRV in the intubated COVID-19 group
Measured: 01/06/2021
Secondary Outcome 9
To correlate the ICP pulse waveform and the neurological symptoms on hospital admission in the intubated COVID-19 group
Measured: 01/06/2021
Secondary Outcome 10
To correlate the ICP pulse waveform and the outcome at hospital discharge in the intubated COVID-19 group
Measured: 01/06/2021
Secondary Outcome 11
To correlate the ICP pulse waveform and to neuroimaging when available in the intubated COVID-19 group
Measured: 01/06/2021
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2021
- Study start30 Apr 2020
- Primary completion15 Jul 2021
- Study completion15 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Intracranial PressureStudies 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Federal University of São Paulo
- Sponsor type
- University, hospital or other
- Collaborators
- Sens4care
- Responsible party
- Principal investigator, Gisele Sampaio Silva, Federal University of São Paulo
- Investigators
- GISELE GS SILVA, SAMPAIO, Principal investigator, Uf SAO PAULO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04861402
- Sponsor's protocol ID
- 31589920.7.1001.5505
- Status last verified
- Sep 2025
- First submitted
- 25 Apr 2021
- Last updated
- 15 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: There isn't defined a plan to make individual participant data (IPD) available to other researchers yet.
Publications
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24.
PubMed 31978945Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 Mar;579(7798):270-273. doi: 10.1038/s41586-020-2012-7. Epub 2020 Feb 3.
PubMed 32015507Jin Y, Yang H, Ji W, Wu W, Chen S, Zhang W, Duan G. Virology, Epidemiology, Pathogenesis, and Control of COVID-19. Viruses. 2020 Mar 27;12(4):372. doi: 10.3390/v12040372.
PubMed 32230900Su S, Wong G, Shi W, Liu J, Lai ACK, Zhou J, Liu W, Bi Y, Gao GF. Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses. Trends Microbiol. 2016 Jun;24(6):490-502. doi: 10.1016/j.tim.2016.03.003. Epub 2016 Mar 21.
PubMed 27012512Cascella M, Rajnik M, Aleem A, Dulebohn SC, Di Napoli R. Features, Evaluation, and Treatment of Coronavirus (COVID-19). 2023 Aug 18. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK554776/
PubMed 32150360Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000 Sep 1;87(5):E1-9. doi: 10.1161/01.res.87.5.e1.
PubMed 10969042Ye M, Ren Y, Lv T. Encephalitis as a clinical manifestation of COVID-19. Brain Behav Immun. 2020 Aug;88:945-946. doi: 10.1016/j.bbi.2020.04.017. Epub 2020 Apr 10. No abstract available.
PubMed 32283294Paniz-Mondolfi A, Bryce C, Grimes Z, Gordon RE, Reidy J, Lednicky J, Sordillo EM, Fowkes M. Central nervous system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). J Med Virol. 2020 Jul;92(7):699-702. doi: 10.1002/jmv.25915.
PubMed 32314810Santos MB, Silveira AF, Andrade JBC, Rocha EC, Moraes FM, Martins HNF, Rodrigues DLG, Silva GS. Transcranial Doppler findings in patients with COVID-19: a prospective observational study. Arq Neuropsiquiatr. 2026 Jun;84(6):1-9. doi: 10.1055/s-0046-1825526. Epub 2026 Jul 14.
PubMed 42447921
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-Invasive Intracranial Pressure in COVID-19 Individuals
- ClinicalTrials.gov ID
- NCT04861402
- Acronym / sponsor ID
- 31589920.7.1001.5505
- Conditions
- Intracranial Pressure
- Keywords
- Neurocritical care, Infectious Disease Medicine
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Federal University of São PauloUniversity, hospital or other
- Collaborators
- Sens4care
- Study start
- 30 Apr 2020 (actual)
- Primary completion
- 15 Jul 2021 (actual)
- Study completion
- 15 Dec 2021 (actual)
- First posted
- 27 Apr 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.
The use of non-invasive intracranial pressure monitoring, including intracranial pressure pulse morphology in patients with COVID-19, could calculate possible components associated with the presence of neurological symptoms in these patients, in addition to being a tool with the potential to monitor the repercussion of MV at cerebral compliance patient patients. In addition, it is likely that patients with COVID-19 also have cerebral embolization more frequently than healthy patients, which is justified by transcranial doppler ultrasound assessment. The aim of the study is to monitor this brain pressure using a non-invasive method of monitoring, with a helmet-like system in place, for 1 hour for 7 consecutive days. There will be no associated invasive procedure of any kind. Monitoring will be done by the criteria themselves, no place where the patient and the mandatory volunteer. Another objective is to capture signs of microembolisms (small strokes that have not yet manifested) by performing a doppler ultrasound on the head with a helmet also for 1 hour, in a single evaluation.
The study population will include inpatients with COVID-19 infection. The control group will be in patients who do not have Covid-19. The control group will consist of people with similar characteristics and who have not recovered. Patients who meet the inclusion criteria incorporated into the monitoring with a non-invasive intracranial pressure device for 1 hour during hospitalization (Brain4Care® device approved by ANVISA), being monitored for up to seven days, in addition to monitoring for 1 hour with a transcranial doppler ultrasound helmet DWL® in a single assessment. There will be no invasive procedures or other equipment used without due knowledge by Organs competent bodies. It does not collect collection or retention of any biological material.
Detailed description
INTRODUCTION: The Coronavirus Disease 2019 (COVID-19) is an infectious disease transmitted one person to another mainly from cough and sneeze aerosols as well as from contaminated surfaces. The most common respiratory symptoms are dry cough, fever, and dyspnea, but the Severe Respiratory Acute Syndrome (SARS) can be installed increasing disease´s mortality. In addition, neurological symptoms have been described according the increase of severity and age. Changes of intracranial pressure (ICP) can partially explain the Central Nervous System (CNS) impairment due to COVID-19. The ICP waveform can bring relevant information about intracranial compliance, and, nowadays, it can be measured by non-invasive technology. Clinically, non-invasive ICP waveform assessment would help to understand the repercussion of Invasive Mechanical Ventilation (IMV) on CNS in COVID-19 persons. AIMS: This study aims to evaluate the ICP waveform in intubated and non-intubated COVID-19 persons. Furthermore, the association between ICP and IMV parameters, level of sedation, heart rate variability, neurological symptoms, neuroimage, and final discharge will be investigated. . METHODS: At least 30 COVID-19 individuals will be included within 72h from admission and 14 days from symptoms onset. They will be divided into two groups: non-intubated (n=15) and intubated, paired with non-COVID-19 ones (non-intubated and intubated non-COVID-19 groups, respectively). The non-invasive ICP monitoring will be daily performed for 7 consecutive days. The Brain4Care's device and Analytic System will be used to assess the three pulse peaks (P1, 2 and 3) at the ICP waveform. The following variables will be investigated: P1 and P2 amplitude, P2/P1 ratio, time to peak and time percentage of P2 higher than P1. For statistics, all variables will be tested as to their normal or non-normal distribution through appropriate statical analyzes. For basic demographic and clinical variables, descriptive data analysis will be used. The repetitive measurement Anova will be used for ICP outcomes throughout the days. Pearson's or Spearman´s correlations will be applied according to data distribution.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Non-intubated COVID-19 group | – | Device: The ICP monitoring will be performed in a non-invasive method developed by Brain4CareMen and women (not pregnant) Older than 18 years old Diagnosis of COVID-19 confirmed by Reverse Transcription Polymerase Chain Reaction (RT-PCR) Subjects intubated Time between admission and study inclusion ≤ 72h Non-intubated during the monitoring carried out in the study Time between onset symptoms and study inclusion ≤ 14 days No neurological acute disease No cutaneous injury in the head to impossibility the ICP monitoring No cutaneous injury in the head to impossibility the monitoring with the transcranial doppler helmet Patients who have not been submitted to decompressive craniectomy previously. |
| Intubated COVID-19 group | – | Device: The ICP monitoring will be performed in a non-invasive method developed by Brain4CareMen and women (not pregnant) Older than 18 years old Diagnosis of COVID-19 confirmed by Reverse Transcription Polymerase Chain Reaction (RT-PCR) Subjects intubated Time between admission and study inclusion ≤ 72h For intubated group time between IUC admission and study inclusion ≤ 72h Time between onset symptoms and study inclusion ≤ 14 days No neurological acute disease No cutaneous injury in the head to impossibility the ICP monitoring No cutaneous injury in the head to impossibility the monitoring with the transcranial doppler helmet Patients who have not been submitted to decompressive craniectomy previously. |
| Health control group | – | Device: The ICP monitoring will be performed in a non-invasive method developed by Brain4CareMen and women (not pregnant) Older than 18 years old No cutaneous injury in the head to impossibility the ICP monitoring No symptoms of COVID-19 on the last 15 days • For healthy group: No previous neurological disease No chronic disease as Diabetes Mellitus Type 2, Chronic Obstructive Pulmonary Disease (COPD), Heart Failure, hypertension or Chronic Kidney Disease (CKD) No cutaneous injury in the head to impossibility the monitoring with the transcranial doppler helmet Patients who have not been submitted to decompressive craniectomy previously. |
| Non-COVID-19 and non-neurological disease intubated group | – | Device: The ICP monitoring will be performed in a non-invasive method developed by Brain4CareMen and women (not pregnant) Older than 18 years old No cutaneous injury in the head to impossibility the ICP monitoring • For intubated group: ICF signed by the participant or his/her legal representative* Intubated patients for others causes than COVID-19 or neurological diseases IUC admission and study inclusion ≤ 72h No symptoms of COVID-19 on the last 15 days No cutaneous injury in the head to impossibility the monitoring with the transcranial doppler helmet Patients who have not been submitted to decompressive craniectomy previously. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- This is a multicenter longitudinal study of 4 centers in Brazil: Hospital of São Paulo (Federal University of São Paulo), Benemérita Portuguese Charity Association, São Paulo-SP, ESHO Hospital Services Company AS, São Paulo, SP and Federal University of São Carlos, São Carlos-SP, from June to December of 2020. This will follow Helsinki recommendations for human protocols. This study was approved by Federal University of São Paulo's Human Research Ethics Committee (process number 4,050,985). The patients who completed the inclusion criteria (table 1) will be invited to participate, and they will receive an Informed Consent Form (ICF). At least 60 subjects will be included, and they will be equally divided into 4 groups.
Key inclusion criteria (8 listed)
- Men and women (not pregnant) Older than 18 years old Diagnosis of COVID-19 confirmed by Reverse Transcription Polymerase Chain Reaction (RT-PCR) Subjects intubated or non-intubated Time between admission and study inclusion ≤ 72h For intubated group time between IUC admission and study inclusion ≤ 72h Time between onset symptoms and study inclusion ≤ 14 days No neurological acute disease No cutaneous injury in the head to impossibility the ICP monitoring ICF signed by the participant or his/her legal representative*
- No cutaneous injury in the head to impossibility the monitoring with the transcranial doppler helmet Patients who have not been submitted to decompressive craniectomy previously. Subjects intubated or non-intubated For intubated group time between IUC admission and study inclusion ≤ 72h Time between admission and study inclusion ≤ 72h Time between onset symptoms and study inclusion ≤14 days No neurological acute disease
- Men and women (not pregnant) Older than 18 years old No cutaneous injury in the head to impossibility the ICP monitoring • For intubated group: ICF signed by the participant or his/her legal representative Intubated patients for others causes than COVID-19 or neurological diseases IUC admission and study inclusion ≤ 72h No symptoms of COVID-19 on the last 15 days
- For healthy group: No previous neurological disease No chronic disease as Diabetes Mellitus Type 2, Chronic Obstructive Pulmonary Disease (COPD), Heart Failure, hypertension or Chronic Kidney Disease (CKD)
- No cutaneous injury in the head to impossibility the monitoring with the transcranial doppler helmet Patients who have not been submitted to decompressive craniectomy previously.
Key exclusion criteria (1 listed)
- It will be excluded those who asked to stop their participation, and those with problems in acquiring ICP data.
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 |
|---|---|---|
| The ICP monitoring will be performed in a non-invasive method developed by Brain4CareAlso: The presence of spontaneous microembolization will be assessed by means of non-invasive monitoring by transcranial dopplerThe ICP monitoring will be performed in a non-invasive way through the cranial deformation method developed by Brain4Care Inc. The selected patients will be monitored until 1h/day for 7 sequential days or even discharge. The clinical outcomes such as ventilatory status will be noted (if the subject is under oxygen supplementation, using non-invasive mechanical ventilation or intubated), the ventilatory parameters during the monitorization will be analyzed in the intubated group (or those from a non-intubated group who was intubated during the seven days of hospitalization) including IFO2, CV, PEEP, driving pressure, and pressure plate as well as ventilatory asynchronies. Some changes in ventilatory parameters during monitorization will be noted. These procedures will be applied to all groups, excepted to the healthy group. This last group will be monitored only once for 30 minutes at the Federal University of São Carlos (UFSCar). | Device | Health control group, Intubated COVID-19 group, Non-COVID-19 and non-neurological disease intubated group, Non-intubated COVID-19 group |
Primary outcome
ICP pulse waveform
Time frame: 01/06/2021
To evaluate the ICP pulse waveform in patients with COVID-19 non-intubated compared to healthy subjects.
ICP pulse waveform 2
Time frame: 01/06/2021
To evaluate the ICP pulse waveform in intubated patients with COVID-19 compared to intubated subjects with other diagnoses except COVID-19.
spontaneous microemboli
Time frame: 01/06/2021
To evaluate the spontaneous microemboli presence with TCD in those subjects who received the ICP monitoring.
12 secondary outcomes
Secondary Outcome
Time frame: 01/06/21
Secondary Outcome 1
Time frame: 01/06/2021
Secondary Outcome 2
Time frame: 01/06/2021
Secondary Outcome 3
Time frame: 01/06/2021
Secondary Outcome 4
Time frame: 01/06/2021
Secondary Outcome 5
Time frame: 01/06/2021
Secondary Outcome 6
Time frame: 01/06/2021
Secondary Outcome 7
Time frame: 01/06/2021
Secondary Outcome 8
Time frame: 01/06/2021
Secondary Outcome 9
Time frame: 01/06/2021
Secondary Outcome 10
Time frame: 01/06/2021
Secondary Outcome 11
Time frame: 01/06/2021
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2025.
- Results publication: PubMed 31978945Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24.
- Results publication: PubMed 32015507Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 Mar;579(7798):270-273. doi: 10.1038/s41586-020-2012-7. Epub 2020 Feb 3.
- Results publication: PubMed 32230900Jin Y, Yang H, Ji W, Wu W, Chen S, Zhang W, Duan G. Virology, Epidemiology, Pathogenesis, and Control of COVID-19. Viruses. 2020 Mar 27;12(4):372. doi: 10.3390/v12040372.
- Results publication: PubMed 27012512Su S, Wong G, Shi W, Liu J, Lai ACK, Zhou J, Liu W, Bi Y, Gao GF. Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses. Trends Microbiol. 2016 Jun;24(6):490-502. doi: 10.1016/j.tim.2016.03.003. Epub 2016 Mar 21.
- Results publication: PubMed 32150360Cascella M, Rajnik M, Aleem A, Dulebohn SC, Di Napoli R. Features, Evaluation, and Treatment of Coronavirus (COVID-19). 2023 Aug 18. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK554776/
- Results publication: PubMed 10969042Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000 Sep 1;87(5):E1-9. doi: 10.1161/01.res.87.5.e1.
- Results publication: PubMed 32283294Ye M, Ren Y, Lv T. Encephalitis as a clinical manifestation of COVID-19. Brain Behav Immun. 2020 Aug;88:945-946. doi: 10.1016/j.bbi.2020.04.017. Epub 2020 Apr 10. No abstract available.
- Results publication: PubMed 32314810Paniz-Mondolfi A, Bryce C, Grimes Z, Gordon RE, Reidy J, Lednicky J, Sordillo EM, Fowkes M. Central nervous system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). J Med Virol. 2020 Jul;92(7):699-702. doi: 10.1002/jmv.25915.
- Derived from this study: PubMed 42447921Santos MB, Silveira AF, Andrade JBC, Rocha EC, Moraes FM, Martins HNF, Rodrigues DLG, Silva GS. Transcranial Doppler findings in patients with COVID-19: a prospective observational study. Arq Neuropsiquiatr. 2026 Jun;84(6):1-9. doi: 10.1055/s-0046-1825526. Epub 2026 Jul 14.
- Individual participant dataSharing planned: Yes. There isn't defined a plan to make individual participant data (IPD) available to other researchers yet.
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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.
GISELE GS SILVA, SAMPAIO principal investigator
Uf SAO PAULO
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Intracranial Pressure, run by Federal University of São Paulo at 1 site in Brazil.
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 8 inclusion and 1 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: finished, as of the sponsor's last update on 15 Sep 2025. 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 Brazil. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
ICP pulse waveform (time frame: 01/06/2021). The study lists 3 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 NCT04861402, which also lists 9 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 15 Sep 2025.