Critical IllnessSepCeaseNCT03311568
Microcirculatory Alterations in Critical Disease: New Ultrasound Technology
A study testing ultrasound for microcirculatory assessment in people with Critical Illness and Septic Shock, run by St. Olavs Hospital at 1 site in Norway.
Trial summary
Aim of this study is (1) to test and further develop a new non-invasive ultrasound method, and (2) to gain new insight into microcirculatory alterations during critical disease, particularly in critical septic shock patients. Read more about this study
- Who is it for?
- Ages 20 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Critical Illness, Septic Shock
- What is being tested?
- ultrasound for microcirculatory assessment
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteNorway
- Study dates
- 31 Oct 2017to 1 Nov 2019
- 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 20 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- healthy volunteers: No disease, no medication, no history of cardiovascular events, no smoking, body mass index (BMI) 20-35 kg/m2, no premature cardiovascular disease among parents.
- patients scheduled for non-thoracic surgery in general anesthesia: BMI 20-35 kg/m2, surgery scheduled for general anaesthesia/narcosis without any expected complications. Typical candidates: Laparotomy/laparoscopy. Cholecystectomy, adnexectomy, hysterectomy. No disease other than the indication for surgery, no medication other than those needed for the present condition demanding surgery, e.g. antibiotics, pain medicine.
- scheduled for open-chest cardiac surgery, Age < 60 years, BMI 20-35 kg/m2, no diagnosed peripheral artery disease, no history of cardiovascular events other than those indicating the actual surgery - 'as healthy as possible', meaning no previous cardiac surgery, no cerebral vascular events, no diagnosed peripheral artery disease. These patients mostly have a history of hypertension, diabetes, hypercholesterolaemia, myocardial infarction or at least angina pectoris, as well as the associated medical therapy. Typical candidates: Coronary artery disease patients without other diagnosed vascular disease.
- septic shock defined as 1) suspected infection, and 2) an acute change in the 'Sequential (Sepsis-Related) Organ Failure Assessment' score (SOFA) of two or more points and serum-lactate acid above 2mmol/l and 3) at least one vasopressor (strong blood-pressure stimulating medical infusion) required to maintain mean blood pressure (MAP) above 65 mmHg, despite adequate fluid resuscitation. Mechanical ventilation ('Respirator'). Advanced invasive haemodynamic monitoring including continuous invasive arterial blood pressure, central venous pressure, pulmonary artery pressure (pulmonary artery catheter/ 'Swan Ganz'), cardiac output and systemic vascular resistance monitoring, as well as circulatory parameters associated with these monitoring systems. Frequent non-invasive cardiac ultrasound - echocardiography ('Echo'). Typical candidates: Critical disease ICU patients with suspected septic shock.
Who cannot join
- Healthy volunteers: Pregnancy, age > 40 years or < 20 years, BMI < 20 or BMI > 35, history of cardiovascular disease, diabetes or hypertension or previous/ongoing pharmacological/non-pharmacological therapy for such diseases. Hereditary vascular disease or connective tissue disease. Skin disease suspected to be influenced by or to influence US registrations (skin-probe interactions)
- non-thoracic surgery: Pregnancy, age > 40 years, BMI < 20 or BMI > 35, smoking, history of cardiovascular disease/events, diabetes or hypertension or previous/ongoing pharmacological/non-pharmacological therapy for such diseases. Hereditary vascular disease or connective tissue disease. Skin disease suspected to be influenced by or to influence US registrations (skin-probe interactions).
- open-chest cardiac surgery: Pregnancy, age > 60 years, BMI < 20 or BMI > 35, history of open chest cardiac surgery. Hereditary vascular disease or connective tissue disease.
- septic shock: Pregnancy. History of heart failure and ongoing medical therapy for such disease. Hereditary vascular disease or connective tissue disease. Palliative or proliferated cancer disease. Advanced skin disease complicating performance of the US registrations. Isolated contagious patients and patients isolated due to a pronounced immune-suppressed state of health.
- General: study equipment or ultrasound registrations are suspected to disturb patient treatment
- General: consent refused by patient or (in case of septic shock) by family member next to kin
Trial locations and contacts
1 site in 1 country.
Norway1 site
St Olavs Hospital, Dept Gastrointestinal Surgery, Dept Thoracic Surgery, Dept Intensive Care Medicine
Trondheim
About this study
Official title: Microcirculatory Alterations in Critical Disease. New Ultrasound Technology for Assessment of Small-vessel Circulation Pathophysiology
Aim of this study is (1) to test and further develop a new non-invasive ultrasound method, and (2) to gain new insight into microcirculatory alterations during critical disease, particularly in critical septic shock patients.
Although early identification and treatment of sepsis have had top priority among the working tasks of the international 'Surviving Sepsis Campaign' society (collaboration of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine) for several years, which have led to improved survival over the last two decades, there is no objective validated diagnostic test to identify or to support the clinical diagnosis at an early stage. Analogous, there is no validated monitoring system available to guide and evaluate the effects of stabilizing measurements in sepsis, or other critical disease, at the microcirculatory level. And thus, there is an enormous knowledge gap regarding dynamic changes at the microcirculatory level during sepsis and other critical disease.
Goal with this study is to investigate the robustness of this new US-technology, regarding its ability to identify and monitor critical microcirculatory impairment during critical disease. The investigators believe this technology may improve early diagnosis and thus early initiation of adequate treatment in septic shock. Its mobile and non-invasive qualities, as in most ultrasound methods, substantiate its availability to a wide range of clinical settings.
Read the detailed description
Critical disease, e.g. life threatening septic shock triggered from infections with multiorgan failure, demands aggressive medical treatment in specialized intensive care units (ICU). Incidences and mortality of sepsis vary significant, depending on regional medical culture, diagnostic criteria and the time span and method of data collection.
Common clinical appearance of critical disease is often life threatening low blood pressure, impaired consciousness up to coma, abnormal breathing patterns, and then subsequently secondary organ failures which further increases mortality. The influence of these 'macro-haemodynamic symptoms', i.e. physiologic aberrations that can be assessed using standard patient monitoring systems, on the tissue micro-circulation where organ damage and finally cell death occurs, is only indirectly available for assessment. Basically, the coarse therapeutic approach to circulatory shock is to normalize macro-haemodynamic parameters, without any robust method to evaluate and monitor micro-circulatory effects. Thus, following current guidelines and clinical practice, it is sometimes not known for sure, on an individual basis, whether treatment and stabilization measures increase survival chances.
Studies of the microcirculation have been performed using invasive micro-dialysis, direct orthogonal polarization spectral imaging and direct side-stream dark-field microscopy. The wide use of these methods is challenged by the fact that they are very expensive and demand extended operator expertise.
The investigators think there is sufficient evidence to claim that further improvement in early diagnostic and therapy guidance of sepsis, septic shock and other critical disease, depends on increased knowledge of microcirculatory alterations, and widespread affordable technical solutions to detect and monitor the course of sepsis and other critical disease at the microcirculatory level.
At the Norwegian University of Technology and Science (NTNU), Department of Circulation and Medical Imaging (ISB), new ultrasound technology has been developed by Professor Hans Torp, which may offer an operator-independent, affordable and non-invasive method to evaluate microcirculation in humans.
In general, ultrasound is unique in that sense that it facilitates non-invasive imaging of anatomy and physiology. The unique with this new probe is the emittance of ultrasound waves from the whole cross-section of the probe surface.
To describe the expected spectrum of microcirculatory impairment during different stages of sepsis, septic shock and comparable critical disease, firstly US registrations are needed from persons with known normal microcirculation. Then, registrations of normal microcirculation are needed in persons exposed to increasing amounts of circulatory stress. Finally, microcirculatory conditions will be observed in patients with critical septic shock. Thus, firstly healthy volunteers are included, then stabile patients undergoing major planned surgery, and finally patients in critical septic shock demanding advanced intensive care treatment and monitoring.
- Conditions
- Critical Illness, Septic Shock
- Being tested
- ultrasound for microcirculatory assessment
- Keywords
- Ultrasonography, Microvessels, Physiopathology, Diagnostic Imaging, Critical Care
- Medical subject headings
- Critical Illness, Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ultrasound for microcirculatory assessmentDevice
Ultrasound for microcirculatory assessment Repeated measurements within study participants for analysis of variance and explorative analyses of ultrasound signals, to identify most suitable parameters to describe microcirculatory alterations in critical disease, especially in sepsis.
Analyse blood flow velocities in several depths and from several vessels of different sizes simultaneously
US registration repeated within each study participant consecutively on seven different regions of the body surface.
| Study group | Role | What they receive |
|---|---|---|
| surgery in general anaesthesia | Experimental | 10 patients. ultrasound for microcirculatory assessment applied. Receives: Device: ultrasound for microcirculatory assessment |
| open chest cardiac surgery | Experimental | 10 patients. ultrasound for microcirculatory assessment applied. Receives: Device: ultrasound for microcirculatory assessment |
| critical septic shock at ICU | Experimental | 20 patients. ultrasound for microcirculatory assessment applied. Receives: Device: ultrasound for microcirculatory assessment |
| healthy volunteers | Experimental | 10 subjects. ultrasound for microcirculatory assessment applied. Receives: Device: ultrasound for microcirculatory assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pulsatile index
(velocity max - velocity min) / mean velocity
Measured: 1 day
Time-velocity-integral
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2017
- Study start31 Oct 2017
- Primary completion1 Nov 2019
- Study completion1 Nov 2019
Why it stopped: Researcher has quit. Question still unanswered. A related study (observational, not to be registered) has started recently.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Critical IllnessStudies of the same condition, open and under way.
- More trials run by St. Olavs HospitalThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Single group
- Model description
- Prospective observational study. Validation of a new non-invasive ultrasound device in four controlled categories of study participants.
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Olavs Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Norwegian University of Science and Technology
- Responsible party
- Sponsor
- Investigators
- Hans Torp, prof, Study chair, Norwegian University of Science and TechnologyDaniel Bergum, md phd, Principal investigator, St. Olavs Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03311568
- Sponsor's protocol ID
- 2017/908
- Acronym
- SepCease
- Status last verified
- Sep 2020
- First submitted
- 11 Oct 2017
- Last updated
- 18 Sep 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Microcirculatory Alterations in Critical Disease. New Ultrasound Technology for Assessment of Small-vessel Circulation Pathophysiology
- ClinicalTrials.gov ID
- NCT03311568
- Acronym / sponsor ID
- SepCease / 2017/908
- Conditions
- Critical Illness, Septic Shock
- Keywords
- Ultrasonography, Microvessels, Physiopathology, Diagnostic Imaging, Critical Care
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Researcher has quit. Question still unanswered. A related study (observational, not to be registered) has started recently.
- Enrolment
- 30 participants (actual)
- Lead sponsor
- St. Olavs HospitalUniversity, hospital or other
- Collaborators
- Norwegian University of Science and Technology
- Study start
- 31 Oct 2017 (actual)
- Primary completion
- 1 Nov 2019 (actual)
- Study completion
- 1 Nov 2019 (actual)
- First posted
- 17 Oct 2017 (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.
Aim of this study is (1) to test and further develop a new non-invasive ultrasound method, and (2) to gain new insight into microcirculatory alterations during critical disease, particularly in critical septic shock patients.
Although early identification and treatment of sepsis have had top priority among the working tasks of the international 'Surviving Sepsis Campaign' society (collaboration of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine) for several years, which have led to improved survival over the last two decades, there is no objective validated diagnostic test to identify or to support the clinical diagnosis at an early stage. Analogous, there is no validated monitoring system available to guide and evaluate the effects of stabilizing measurements in sepsis, or other critical disease, at the microcirculatory level. And thus, there is an enormous knowledge gap regarding dynamic changes at the microcirculatory level during sepsis and other critical disease.
Goal with this study is to investigate the robustness of this new US-technology, regarding its ability to identify and monitor critical microcirculatory impairment during critical disease. The investigators believe this technology may improve early diagnosis and thus early initiation of adequate treatment in septic shock. Its mobile and non-invasive qualities, as in most ultrasound methods, substantiate its availability to a wide range of clinical settings.
Detailed description
Critical disease, e.g. life threatening septic shock triggered from infections with multiorgan failure, demands aggressive medical treatment in specialized intensive care units (ICU). Incidences and mortality of sepsis vary significant, depending on regional medical culture, diagnostic criteria and the time span and method of data collection.
Common clinical appearance of critical disease is often life threatening low blood pressure, impaired consciousness up to coma, abnormal breathing patterns, and then subsequently secondary organ failures which further increases mortality. The influence of these 'macro-haemodynamic symptoms', i.e. physiologic aberrations that can be assessed using standard patient monitoring systems, on the tissue micro-circulation where organ damage and finally cell death occurs, is only indirectly available for assessment. Basically, the coarse therapeutic approach to circulatory shock is to normalize macro-haemodynamic parameters, without any robust method to evaluate and monitor micro-circulatory effects. Thus, following current guidelines and clinical practice, it is sometimes not known for sure, on an individual basis, whether treatment and stabilization measures increase survival chances.
Studies of the microcirculation have been performed using invasive micro-dialysis, direct orthogonal polarization spectral imaging and direct side-stream dark-field microscopy. The wide use of these methods is challenged by the fact that they are very expensive and demand extended operator expertise.
The investigators think there is sufficient evidence to claim that further improvement in early diagnostic and therapy guidance of sepsis, septic shock and other critical disease, depends on increased knowledge of microcirculatory alterations, and widespread affordable technical solutions to detect and monitor the course of sepsis and other critical disease at the microcirculatory level.
At the Norwegian University of Technology and Science (NTNU), Department of Circulation and Medical Imaging (ISB), new ultrasound technology has been developed by Professor Hans Torp, which may offer an operator-independent, affordable and non-invasive method to evaluate microcirculation in humans.
In general, ultrasound is unique in that sense that it facilitates non-invasive imaging of anatomy and physiology. The unique with this new probe is the emittance of ultrasound waves from the whole cross-section of the probe surface.
To describe the expected spectrum of microcirculatory impairment during different stages of sepsis, septic shock and comparable critical disease, firstly US registrations are needed from persons with known normal microcirculation. Then, registrations of normal microcirculation are needed in persons exposed to increasing amounts of circulatory stress. Finally, microcirculatory conditions will be observed in patients with critical septic shock. Thus, firstly healthy volunteers are included, then stabile patients undergoing major planned surgery, and finally patients in critical septic shock demanding advanced intensive care treatment and monitoring.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Prospective observational study. Validation of a new non-invasive ultrasound device in four controlled categories of study participants.
| Arm | Type | Receives |
|---|---|---|
| surgery in general anaesthesia | Experimental | Device: ultrasound for microcirculatory assessment10 patients. ultrasound for microcirculatory assessment applied. |
| open chest cardiac surgery | Experimental | Device: ultrasound for microcirculatory assessment10 patients. ultrasound for microcirculatory assessment applied. |
| critical septic shock at ICU | Experimental | Device: ultrasound for microcirculatory assessment20 patients. ultrasound for microcirculatory assessment applied. |
| healthy volunteers | Experimental | Device: ultrasound for microcirculatory assessment10 subjects. ultrasound for microcirculatory assessment applied. |
Who may qualify
- Ages
- 20 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- healthy volunteers: No disease, no medication, no history of cardiovascular events, no smoking, body mass index (BMI) 20-35 kg/m2, no premature cardiovascular disease among parents.
- patients scheduled for non-thoracic surgery in general anesthesia: BMI 20-35 kg/m2, surgery scheduled for general anaesthesia/narcosis without any expected complications. Typical candidates: Laparotomy/laparoscopy. Cholecystectomy, adnexectomy, hysterectomy. No disease other than the indication for surgery, no medication other than those needed for the present condition demanding surgery, e.g. antibiotics, pain medicine.
- scheduled for open-chest cardiac surgery, Age < 60 years, BMI 20-35 kg/m2, no diagnosed peripheral artery disease, no history of cardiovascular events other than those indicating the actual surgery - 'as healthy as possible', meaning no previous cardiac surgery, no cerebral vascular events, no diagnosed peripheral artery disease. These patients mostly have a history of hypertension, diabetes, hypercholesterolaemia, myocardial infarction or at least angina pectoris, as well as the associated medical therapy. Typical candidates: Coronary artery disease patients without other diagnosed vascular disease.
- septic shock defined as 1) suspected infection, and 2) an acute change in the 'Sequential (Sepsis-Related) Organ Failure Assessment' score (SOFA) of two or more points and serum-lactate acid above 2mmol/l and 3) at least one vasopressor (strong blood-pressure stimulating medical infusion) required to maintain mean blood pressure (MAP) above 65 mmHg, despite adequate fluid resuscitation. Mechanical ventilation ('Respirator'). Advanced invasive haemodynamic monitoring including continuous invasive arterial blood pressure, central venous pressure, pulmonary artery pressure (pulmonary artery catheter/ 'Swan Ganz'), cardiac output and systemic vascular resistance monitoring, as well as circulatory parameters associated with these monitoring systems. Frequent non-invasive cardiac ultrasound - echocardiography ('Echo'). Typical candidates: Critical disease ICU patients with suspected septic shock.
Key exclusion criteria (6 listed)
- Healthy volunteers: Pregnancy, age > 40 years or < 20 years, BMI < 20 or BMI > 35, history of cardiovascular disease, diabetes or hypertension or previous/ongoing pharmacological/non-pharmacological therapy for such diseases. Hereditary vascular disease or connective tissue disease. Skin disease suspected to be influenced by or to influence US registrations (skin-probe interactions)
- non-thoracic surgery: Pregnancy, age > 40 years, BMI < 20 or BMI > 35, smoking, history of cardiovascular disease/events, diabetes or hypertension or previous/ongoing pharmacological/non-pharmacological therapy for such diseases. Hereditary vascular disease or connective tissue disease. Skin disease suspected to be influenced by or to influence US registrations (skin-probe interactions).
- open-chest cardiac surgery: Pregnancy, age > 60 years, BMI < 20 or BMI > 35, history of open chest cardiac surgery. Hereditary vascular disease or connective tissue disease.
- septic shock: Pregnancy. History of heart failure and ongoing medical therapy for such disease. Hereditary vascular disease or connective tissue disease. Palliative or proliferated cancer disease. Advanced skin disease complicating performance of the US registrations. Isolated contagious patients and patients isolated due to a pronounced immune-suppressed state of health.
- General: study equipment or ultrasound registrations are suspected to disturb patient treatment
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 |
|---|---|---|
| ultrasound for microcirculatory assessmentUltrasound for microcirculatory assessment Repeated measurements within study participants for analysis of variance and explorative analyses of ultrasound signals, to identify most suitable parameters to describe microcirculatory alterations in critical disease, especially in sepsis. Analyse blood flow velocities in several depths and from several vessels of different sizes simultaneously US registration repeated within each study participant consecutively on seven different regions of the body surface. | Device | critical septic shock at ICU, healthy volunteers, open chest cardiac surgery, surgery in general anaesthesia |
Primary outcome
Pulsatile index
Time frame: 1 day
(velocity max - velocity min) / mean velocity
Time-velocity-integral
Time frame: 1 day
Results and safety
The study was stopped early (reason given: Researcher has quit. Question still unanswered. A related study (observational, not to be registered) has started recently.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2020.
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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.
Hans Torp, prof study chair
Norwegian University of Science and Technology
Daniel Bergum, md phd principal investigator
St. Olavs Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ultrasound for microcirculatory assessment in people with Critical Illness and Septic Shock, run by St. Olavs Hospital at 1 site in Norway.
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 4 inclusion and 6 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 18 Sep 2020. 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 Norway. 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: Researcher has quit. Question still unanswered. A related study (observational, not to be registered) has started recently.). 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?
Pulsatile index (time frame: 1 day). 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?
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 18 Sep 2020.