SepsisPROUD-1NCT04149132
Pulse Photoplethysmography as an Early Tool for the Diagnosis of Sepsis
An observational study of Sepsis, run by Hellenic Institute for the Study of Sepsis at 4 sites in Greece.
Trial summary
Early management of sepsis is associated with better outcome. However, this requires early recognition of the sepsis host. One recently developed customized pulse photoplethysmography (PPG) device manages to measure nitric oxide (NO) that is released from vascular endothelium and seems promising for earlier sepsis… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis
- What is being tested?
- pulse photoplethysmography (PPG) and Measurements of nitric oxide (NO) and malondialdehyde (MDA)
- Type of treatment
- Medical device
- How many people
- 200 participants
- Where
- 4 sitesGreece
- Study dates
- 30 Oct 2019to 30 Jun 2020
- 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
- No healthy volunteers
- Adult, Older adult
Study population: Screening will be done for the inclusion and exclusion criteria in all patients admitted or hospitalized in the participating sites. Participants will be patients meeting all inclusion criteria and none of the exclusion criteria
Who may be able to join
- Age equal to or greater than 18 years
- Both genders
- Written informed consent provided by the patients or by first-degree relatives in case of patients unable to consent.
- Any of two:
- Any infection in a patient with total SOFA score equal to 0 or 1 Patient without sepsis prone to the development of sepsis defined as patients with Charlson's Comorbidity Index (CCI) more than 2 irrespective the reason of admission. These patients are considered prone to infection based on previous findings of our group showing that CCI more than 2 is an independent predisposing factor for sepsis
Who cannot join
- Age below 18 years
- Denial to consent
- Any stage 4 malignancy
- Any do not resuscitate decision
- Active tuberculosis (TB) as defined by the co-administration of drugs for the treatment of TB
- Pregnancy or lactation
Trial locations and contacts
4 sites in 1 country.
Greece4 sites
Intensive Care Unit, "Korgialenio - Benakio" General Hospital of Athens
Athens, 11526
Department of Clinical Therapeutics, "Alexandra" General Hospital of Athens, National and Kapodistrian University of Athens, Medical School
Athens, 11528
2nd Department of Critical Care, "Attikon" University Hospital, National and Kapodistrian University of Athens, Medical School
Athens, 12462
4th Department of Internal Medicine, "Attikon" University Hospital, National and Kapodistrian University of Athens, Medical School
Athens, 12462
About this study
Early management of sepsis is associated with better outcome. However, this requires early recognition of the sepsis host. One recently developed customized pulse photoplethysmography (PPG) device manages to measure nitric oxide (NO) that is released from vascular endothelium and seems promising for earlier sepsis diagnosis than conventional approaches. Aim of the project To evaluate the diagnostic performance of the PPG device for the early diagnosis of sepsis is to evaluate the diagnostic performance of the PPG device for the early diagnosis of sepsis
Read the detailed description
Sepsis is a life-threatening syndrome and the most common cause of death nowadays. This syndrome develops as a result of the dysregulated host response to an infectious insult. As such the mainstay of treatment is the early administration of antimicrobials leading to early eradication of the offending pathogen. However, in this statement the key-feature is the definition of what "early" means. Using the retrospective analysis of data associating final outcome from septic shock with the delay in start of antimicrobials from the start of vasopressors in 2713 patients with septic shock, it was found that 79.1% of patients in which this delay was less than one hour survived. Every further hour of delay in start of antibiotics led to 7.6% increase of the risk for unfavorable outcome. These findings were later confirmed from two other analyses. These findings generate two thoughts: a) the above results are based on early recognition of hospital-acquired sepsis that was achievable only because these studies were done in an Intensive Care Unit (ICU) environment in patients under close monitoring. However, early sepsis recognition for a newly admitted patient remains an unmet need; b) all the above results are coming from patients with septic shock where diagnosis had already been established since patients were already on vasopressors.
It is reasonable to hypothesize that if sepsis had been recognized even earlier final outcome would have been even better. Sanmina have developed a non-invasive technique for the measurement of endothelial released nitric oxide (NO) through customized pulse photoplethysmography (PPG). Since NO is released by the vascular endothelium early in the pathogenesis of sepsis it is reasonable to hypothesize that PPG is a technique that can early inform on the risk for a patient with suspicion of an infection to develop sepsis. The time of measurement is less than two minutes. Preliminary data show that the reading of a healthy subject of eight consecutive minutes cannot trace any increase of NO; in sepsis a peak of more than 200 units is shown within the first 40 seconds of measurement.
The development of PPG as a tool for the early diagnosis of sepsis requires a two-stage approach. The first stage is based on the association of PPG readings with the change of the SOFA (sequential organ failure assessment) score and vital signs to define if among patients who eventually develop sepsis, PPG changes will be produced earlier than changes of SOFA scores and of vital signs.
- Conditions
- Sepsis
- Being tested
- pulse photoplethysmography (PPG), Measurements of nitric oxide (NO) and malondialdehyde (MDA)
- Keywords
- early diagnosis, infection, pulse photoplethysmography
- Medical subject headings
- Sepsis, Disease, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pulse photoplethysmography (PPG)Device
PPG and systolic blood pressure recording will be performed every two hours for three consecutive days. PPG reading will last two minutes and peaks of NO productions will be captured. Day 1 is considered the day of signing the informed consent followed by the first recording. On the first PPG recording of the same days i.e. on days 1, 2 and 3 the investigators will collect blood from the patients
Measurements of nitric oxide (NO) and malondialdehyde (MDA)Diagnostic test
On the first PPG recording of the same days i.e. on days 1, 2 and 3 the investigators will collect blood from the patients. NO will be measured in serum samples by the Griess reaction. MDA that is considered an index of oxidant status will be measured in serum samples by the thiobarbiturate assay and analysis by high-performance liquid chromatography (HPLC)
| Study group | Role | What they receive |
|---|---|---|
| Patients without sepsis | Patients admitted and hospitalized for infections without sepsis and for other reasons in departments of Internal Medicine and Intensive Care Units Receives: Device: pulse photoplethysmography (PPG); Diagnostic Test: Measurements of nitric oxide (NO) and malondialdehyde (MDA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sensitivity of PPG for the diagnosis of sepsis.
Sensitivity of PPG for the diagnosis of sepsis.
Measured: 72 hours
Secondary outcomes (7)
Correlation of PPG (absolute number) with qSOFA score (absolute number)
Correlation of PPG (absolute number) with qSOFA score (absolute number)
Measured: 72 hours
Correlation of PPG (absolute number) with SOFA score (absolute number)
Correlation of PPG (absolute number) with SOFA score (absolute number)
Measured: 72 hours
Correlation of time (in minutes) of sepsis diagnosis between PPG (absolute number) and SOFA score (absolute number)
Correlation of time (in minutes) of sepsis diagnosis between PPG (absolute number) and SOFA score (absolute number)
Measured: 72 hours
Correlation of time (in minutes) of sepsis diagnosis between PPG (absolute number) and hypotension (mmHg)
Correlation of time (in minutes) of sepsis diagnosis between PPG (absolute number) and hypotension (mmHg)
Measured: 72 hours
The specificity, positive predictive value (PPV) and negative predictive value (NPV) of PPG for the diagnosis of sepsis
The specificity, positive predictive value (PPV) and negative predictive value (NPV) of PPG for the diagnosis of sepsis
Measured: 72 hours
The sensitivity, specificity, PPV and NPV of PPG for the prognosis of 28-day outcome
The sensitivity, specificity, PPV and NPV of PPG for the prognosis of 28-day outcome
Measured: 28 days
Correlation of PPG (absolute number) with circulating levels of NO (μmol/l) and MDA (μmol/l)
The association between PPG and circulating levels of NO and MDA
Measured: 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2019
- Study start30 Oct 2019
- Primary completion30 May 2020
- Study completion30 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SepsisStudies 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hellenic Institute for the Study of Sepsis
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Antonios Papadopoulos, MD, PhD, Principal investigator, 4th Department of Internal Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04149132
- Sponsor's protocol ID
- PROUD-1
- Acronym
- PROUD-1
- Status last verified
- Jul 2020
- First submitted
- 29 Oct 2019
- Last updated
- 29 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pulse Photoplethysmography as an Early Tool for the Diagnosis of Sepsis
- ClinicalTrials.gov ID
- NCT04149132
- Acronym / sponsor ID
- PROUD-1 / PROUD-1
- Conditions
- Sepsis
- Keywords
- early diagnosis, infection, pulse photoplethysmography
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Hellenic Institute for the Study of SepsisUniversity, hospital or other
- Study start
- 30 Oct 2019 (actual)
- Primary completion
- 30 May 2020 (actual)
- Study completion
- 30 Jun 2020 (actual)
- First posted
- 4 Nov 2019 (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.
Early management of sepsis is associated with better outcome. However, this requires early recognition of the sepsis host. One recently developed customized pulse photoplethysmography (PPG) device manages to measure nitric oxide (NO) that is released from vascular endothelium and seems promising for earlier sepsis diagnosis than conventional approaches. Aim of the project To evaluate the diagnostic performance of the PPG device for the early diagnosis of sepsis is to evaluate the diagnostic performance of the PPG device for the early diagnosis of sepsis
Detailed description
Sepsis is a life-threatening syndrome and the most common cause of death nowadays. This syndrome develops as a result of the dysregulated host response to an infectious insult. As such the mainstay of treatment is the early administration of antimicrobials leading to early eradication of the offending pathogen. However, in this statement the key-feature is the definition of what "early" means. Using the retrospective analysis of data associating final outcome from septic shock with the delay in start of antimicrobials from the start of vasopressors in 2713 patients with septic shock, it was found that 79.1% of patients in which this delay was less than one hour survived. Every further hour of delay in start of antibiotics led to 7.6% increase of the risk for unfavorable outcome. These findings were later confirmed from two other analyses. These findings generate two thoughts: a) the above results are based on early recognition of hospital-acquired sepsis that was achievable only because these studies were done in an Intensive Care Unit (ICU) environment in patients under close monitoring. However, early sepsis recognition for a newly admitted patient remains an unmet need; b) all the above results are coming from patients with septic shock where diagnosis had already been established since patients were already on vasopressors.
It is reasonable to hypothesize that if sepsis had been recognized even earlier final outcome would have been even better. Sanmina have developed a non-invasive technique for the measurement of endothelial released nitric oxide (NO) through customized pulse photoplethysmography (PPG). Since NO is released by the vascular endothelium early in the pathogenesis of sepsis it is reasonable to hypothesize that PPG is a technique that can early inform on the risk for a patient with suspicion of an infection to develop sepsis. The time of measurement is less than two minutes. Preliminary data show that the reading of a healthy subject of eight consecutive minutes cannot trace any increase of NO; in sepsis a peak of more than 200 units is shown within the first 40 seconds of measurement.
The development of PPG as a tool for the early diagnosis of sepsis requires a two-stage approach. The first stage is based on the association of PPG readings with the change of the SOFA (sequential organ failure assessment) score and vital signs to define if among patients who eventually develop sepsis, PPG changes will be produced earlier than changes of SOFA scores and of vital signs.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients without sepsis | – | Device: pulse photoplethysmography (PPG), Diagnostic Test: Measurements of nitric oxide (NO) and malondialdehyde (MDA)Patients admitted and hospitalized for infections without sepsis and for other reasons in departments of Internal Medicine and Intensive Care Units |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Screening will be done for the inclusion and exclusion criteria in all patients admitted or hospitalized in the participating sites. Participants will be patients meeting all inclusion criteria and none of the exclusion criteria
Key inclusion criteria (5 listed)
- Age equal to or greater than 18 years
- Both genders
- Written informed consent provided by the patients or by first-degree relatives in case of patients unable to consent.
- Any of two:
- Any infection in a patient with total SOFA score equal to 0 or 1 Patient without sepsis prone to the development of sepsis defined as patients with Charlson's Comorbidity Index (CCI) more than 2 irrespective the reason of admission. These patients are considered prone to infection based on previous findings of our group showing that CCI more than 2 is an independent predisposing factor for sepsis
Key exclusion criteria (6 listed)
- Age below 18 years
- Denial to consent
- Any stage 4 malignancy
- Any do not resuscitate decision
- Active tuberculosis (TB) as defined by the co-administration of drugs for the treatment of TB
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 |
|---|---|---|
| pulse photoplethysmography (PPG)PPG and systolic blood pressure recording will be performed every two hours for three consecutive days. PPG reading will last two minutes and peaks of NO productions will be captured. Day 1 is considered the day of signing the informed consent followed by the first recording. On the first PPG recording of the same days i.e. on days 1, 2 and 3 the investigators will collect blood from the patients | Device | Patients without sepsis |
| Measurements of nitric oxide (NO) and malondialdehyde (MDA)On the first PPG recording of the same days i.e. on days 1, 2 and 3 the investigators will collect blood from the patients. NO will be measured in serum samples by the Griess reaction. MDA that is considered an index of oxidant status will be measured in serum samples by the thiobarbiturate assay and analysis by high-performance liquid chromatography (HPLC) | Diagnostic test | Patients without sepsis |
Primary outcome
Sensitivity of PPG for the diagnosis of sepsis.
Time frame: 72 hours
Sensitivity of PPG for the diagnosis of sepsis.
7 secondary outcomes
Correlation of PPG (absolute number) with qSOFA score (absolute number)
Time frame: 72 hours
Correlation of PPG (absolute number) with SOFA score (absolute number)
Time frame: 72 hours
Correlation of time (in minutes) of sepsis diagnosis between PPG (absolute number) and SOFA score (absolute number)
Time frame: 72 hours
Correlation of time (in minutes) of sepsis diagnosis between PPG (absolute number) and hypotension (mmHg)
Time frame: 72 hours
The specificity, positive predictive value (PPV) and negative predictive value (NPV) of PPG for the diagnosis of sepsis
Time frame: 72 hours
The sensitivity, specificity, PPV and NPV of PPG for the prognosis of 28-day outcome
Time frame: 28 days
Correlation of PPG (absolute number) with circulating levels of NO (μmol/l) and MDA (μmol/l)
Time frame: 72 hours
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 29 Jul 2020.
- Individual participant dataSharing planned: Undecided
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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.
Antonios Papadopoulos, MD, PhD principal investigator
4th Department of Internal Medicine
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sepsis, run by Hellenic Institute for the Study of Sepsis at 4 sites 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 5 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: finished, as of the sponsor's last update on 29 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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 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?
Sensitivity of PPG for the diagnosis of sepsis. (time frame: 72 hours). 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 29 Jul 2020.