Pulmonary EmbolismNCT03887819
Pulmonary Embolism: an Autopsy Study
An observational study of Pulmonary Embolism, run by University of Campania Luigi Vanvitelli.
Trial summary
BACKGROUND: Pulmonary embolism (PE) is associated to high mortality rate worldwide. However, the diagnosis of PE often results inaccurate. Many cases of PE are incorrectly diagnosed or missed and they are often associated to sudden unexpected death (SUD). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Embolism
- What is being tested?
- Hystological evaluation
- How many people
- 15 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2015to 1 Jan 2019
- How long will I take part?
- 24 Months
- 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
- Adult, Older adult
Study population: The study population will include 19 male (63.3%) and 11 female (36.7%). Their age will range from 38 to 87 years.
Who may be able to join
- diagnosis of acute pulmonary embolism;
- patients died after the pulmonary embolic event.
Who cannot join
- diagnosis of non acute pulmonary embolism;
- patients survived after the pulmonary embolic event.
About this study
Official title: The Dating of Thrombus Organization in Cases of Pulmonary Embolism: an Autopsy Study
BACKGROUND: Pulmonary embolism (PE) is associated to high mortality rate worldwide. However, the diagnosis of PE often results inaccurate. Many cases of PE are incorrectly diagnosed or missed and they are often associated to sudden unexpected death (SUD). In forensic practice, it is important to establish the time of thrombus formation in order to determine the precise moment of death. The autopsy remains the gold standard method for the identification of death cause allowing the determination of discrepancies between clinical and autopsy diagnoses. The aim of our study will be to verify the morphological and histological criteria of fatal cases of PE and evaluate the dating of thrombus formation considering 5 ranges of time.
METHODS: Pulmonary vessels sections will be collected from January 2010 to December 2017. Sections of thrombus sampling will be stained with hematoxylin and eosin. The content of infiltrated cells, fibroblasts and collagen fibers will be scored using a semi-quantitative three-point scale of range values.
Hypothesis: After a macroscopic observation and a good sampling traditional histology, it will be important to identify the time of thrombus formation. We will identify histologically a range of time in the physiopathology of the thrombus (early, recent, recent-medium, medium, old), allowing to determine the dating of thrombus formation and the exact time of death.
Read the detailed description
Introduction Venous thromboembolism (VTE) is pathological condition caused by deep vein thrombosis (DVT) with a consequent detaching of thrombus from original sites , that by embolic phenomena and traveling to the lung might result in pulmonary embolism (PE). As first, the diagnosis of PE might result frequently inaccurate, with many cases incorrectly diagnosed or missed. Secondly, it might be caused by several conditions such as surgery and trauma, with a consequent relevant clinical impact and worse prognosis. However, clinical presentation of PE range from those completely asymptomatic or with an insidious disease, to sudden unexpected death (SUD. SUD may be defined as a natural and fatal event that occurs within 1 h of the beginning of symptoms in an apparently healthy subject or in those with a disease not particularly severe to cause an abrupt outcome. Since the diagnosis is challenging, epidemiological data regarding PE mortality remain limited.To date, it is estimated that PE is responsible for 100,000 annual deaths only in the United States and approximately 25-30% of patients had SUD as consequence of PE.
However, in our opinion it might be essential to collect morphological macroscopic evaluation elements to distinguish a thrombus from an embolus or agonic coagulum.To date, the autopsy may be useful for the determination of the identification of death cause, and to establish the dating of transformation of thrombus and evaluate any professional error. Therefore, in this study, authors will critically review the histological section of thrombus from 30 fatal cases of PE pulmonary embolus by autopsies, and its correlation and origin prior or subsequent to a traumatic event, as confirmed by post-mortem examination and final diagnosis. Moreover, the aim of this study will be to evaluate the chronological transformation of the thrombus and to establish the time of death for each subject.
Materials and methods Patients and samples Pulmonary vessels sections will be collected from 30 fatal cases of PE (25 cases of hospitalized patients and 5 cases of SUD) defined according to commonly accepted criteria were routinely collected from January 2010 to December 2017 at the University of Naples Federico II.
Histological evaluation According to the guidelines for autopsy from the Association for European Cardiovascular Pathology, and in all cases authors will examine the pulmonary arterial trunk by posterior approach. Sections (4 μm thick) will be stained with hematoxylin and eosin stain (H\&E) for diagnosis. The original tissues samples will be fixed in 10% neutral buffered formalin and embedded in paraffin. The immunohistochemistry for anti-LCA, anti-CD68, and anti-CD3 will be performed to identify the inflammatory infiltrate. In addition, authors will be performed an immunofluorescence method to identifying the deposition of factor VIII and fibrinogen. A Picro Sirius Red/Fast Green will be used for differential staining of collagen during matrix production phase. All stained samples will be examined under infiltrate, absent or rare lympho-monocytic inflammatory elements. The vessels of small and medium will be involved, mainly from the main branches of the pulmonary vessels.In2 patients we observed a score 3 for cellular infiltrate and 1 for fibrosis. In 10 cases (5 heart patients, 2 cardiac patients undergoing surgery and 3 surgeries), authors will observe an increase (score 2) in the digital and light microscope.
- Conditions
- Pulmonary Embolism
- Being tested
- Hystological evaluation
- Medical subject headings
- Pulmonary Embolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hystological evaluationDiagnostic test
The original tissues samples will be fixed in 10% neutral buffered formalin and embedded in paraffin blocks. Sections (4 μm thick) will be stained with hematoxylin and eosin stain (H\&E) for diagnosis. The immunohistochemistry for anti-LCA, anti-CD68, and anti-CD3 will be performed to identify the inflammatory infiltrate.
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate pulmonary thrombus burden
Authors will evaluate if a pulmonary embolus was originated prior or subsequent to a traumatic event. However, they will evaluate the dimension of the thrombus, and the quantity of fibrinogen present in the thrombus, from pulmonary vessels sections. The tissues samples will be fixed in 10% neutral buffered formalin and embedded in paraffin blocks, and stained with hematoxylin and eosin stain for diagnosis. For inflammatory cellular infiltration and fibrosis, authors will attribute a score 0 for no increase, score 1, 2, or 3 for little, moderate, or high increase of cell content compared to adjacent tissue, respectively. For the extracellular matrix production, authors will attribute a score 0 for absence of collagen production, score 1 and 2 for 10-40% and 40-80% collagen fibers content compared to adjacent normal tissue, respectively, and finally score 3 for wound matrix indistinguishable from adjacent normal tissue.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2019
- Study start1 Jan 2015
- Primary completion1 Jun 2018
- Study completion1 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary EmbolismStudies 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
- 15 participants (actual)
- Target duration
- 24 Months
Sponsor and investigators
- Lead sponsor
- University of Campania Luigi Vanvitelli
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Celestino Sardu, University of Campania Luigi Vanvitelli
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03887819
- Sponsor's protocol ID
- SecondUNI 21.03.2019
- Status last verified
- Mar 2019
- First submitted
- 21 Mar 2019
- Last updated
- 26 Mar 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Mansueto G, Costa D, Capasso E, Varavallo F, Brunitto G, Caserta R, Esposito S, Niola M, Sardu C, Marfella R, Napoli C, Paternoster M. The dating of thrombus organization in cases of pulmonary embolism: an autopsy study. BMC Cardiovasc Disord. 2019 Nov 8;19(1):250. doi: 10.1186/s12872-019-1219-8.
PubMed 31703628
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Dating of Thrombus Organization in Cases of Pulmonary Embolism: an Autopsy Study
- ClinicalTrials.gov ID
- NCT03887819
- Acronym / sponsor ID
- SecondUNI 21.03.2019
- Conditions
- Pulmonary Embolism
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of Campania Luigi VanvitelliUniversity, hospital or other
- Study start
- 1 Jan 2015 (actual)
- Primary completion
- 1 Jun 2018 (actual)
- Study completion
- 1 Jan 2019 (actual)
- First posted
- 25 Mar 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.
BACKGROUND: Pulmonary embolism (PE) is associated to high mortality rate worldwide. However, the diagnosis of PE often results inaccurate. Many cases of PE are incorrectly diagnosed or missed and they are often associated to sudden unexpected death (SUD). In forensic practice, it is important to establish the time of thrombus formation in order to determine the precise moment of death. The autopsy remains the gold standard method for the identification of death cause allowing the determination of discrepancies between clinical and autopsy diagnoses. The aim of our study will be to verify the morphological and histological criteria of fatal cases of PE and evaluate the dating of thrombus formation considering 5 ranges of time.
METHODS: Pulmonary vessels sections will be collected from January 2010 to December 2017. Sections of thrombus sampling will be stained with hematoxylin and eosin. The content of infiltrated cells, fibroblasts and collagen fibers will be scored using a semi-quantitative three-point scale of range values.
Hypothesis: After a macroscopic observation and a good sampling traditional histology, it will be important to identify the time of thrombus formation. We will identify histologically a range of time in the physiopathology of the thrombus (early, recent, recent-medium, medium, old), allowing to determine the dating of thrombus formation and the exact time of death.
Detailed description
Introduction Venous thromboembolism (VTE) is pathological condition caused by deep vein thrombosis (DVT) with a consequent detaching of thrombus from original sites , that by embolic phenomena and traveling to the lung might result in pulmonary embolism (PE). As first, the diagnosis of PE might result frequently inaccurate, with many cases incorrectly diagnosed or missed. Secondly, it might be caused by several conditions such as surgery and trauma, with a consequent relevant clinical impact and worse prognosis. However, clinical presentation of PE range from those completely asymptomatic or with an insidious disease, to sudden unexpected death (SUD. SUD may be defined as a natural and fatal event that occurs within 1 h of the beginning of symptoms in an apparently healthy subject or in those with a disease not particularly severe to cause an abrupt outcome. Since the diagnosis is challenging, epidemiological data regarding PE mortality remain limited.To date, it is estimated that PE is responsible for 100,000 annual deaths only in the United States and approximately 25-30% of patients had SUD as consequence of PE.
However, in our opinion it might be essential to collect morphological macroscopic evaluation elements to distinguish a thrombus from an embolus or agonic coagulum.To date, the autopsy may be useful for the determination of the identification of death cause, and to establish the dating of transformation of thrombus and evaluate any professional error. Therefore, in this study, authors will critically review the histological section of thrombus from 30 fatal cases of PE pulmonary embolus by autopsies, and its correlation and origin prior or subsequent to a traumatic event, as confirmed by post-mortem examination and final diagnosis. Moreover, the aim of this study will be to evaluate the chronological transformation of the thrombus and to establish the time of death for each subject.
Materials and methods Patients and samples Pulmonary vessels sections will be collected from 30 fatal cases of PE (25 cases of hospitalized patients and 5 cases of SUD) defined according to commonly accepted criteria were routinely collected from January 2010 to December 2017 at the University of Naples Federico II.
Histological evaluation According to the guidelines for autopsy from the Association for European Cardiovascular Pathology, and in all cases authors will examine the pulmonary arterial trunk by posterior approach. Sections (4 μm thick) will be stained with hematoxylin and eosin stain (H\&E) for diagnosis. The original tissues samples will be fixed in 10% neutral buffered formalin and embedded in paraffin. The immunohistochemistry for anti-LCA, anti-CD68, and anti-CD3 will be performed to identify the inflammatory infiltrate. In addition, authors will be performed an immunofluorescence method to identifying the deposition of factor VIII and fibrinogen. A Picro Sirius Red/Fast Green will be used for differential staining of collagen during matrix production phase. All stained samples will be examined under infiltrate, absent or rare lympho-monocytic inflammatory elements. The vessels of small and medium will be involved, mainly from the main branches of the pulmonary vessels.In2 patients we observed a score 3 for cellular infiltrate and 1 for fibrosis. In 10 cases (5 heart patients, 2 cardiac patients undergoing surgery and 3 surgeries), authors will observe an increase (score 2) in the digital and light microscope.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 24 Months
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- The study population will include 19 male (63.3%) and 11 female (36.7%). Their age will range from 38 to 87 years.
Key inclusion criteria (2 listed)
- diagnosis of acute pulmonary embolism;
- patients died after the pulmonary embolic event.
Key exclusion criteria (2 listed)
- diagnosis of non acute pulmonary embolism;
- patients survived after the pulmonary embolic event.
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 |
|---|---|---|
| Hystological evaluationThe original tissues samples will be fixed in 10% neutral buffered formalin and embedded in paraffin blocks. Sections (4 μm thick) will be stained with hematoxylin and eosin stain (H\&E) for diagnosis. The immunohistochemistry for anti-LCA, anti-CD68, and anti-CD3 will be performed to identify the inflammatory infiltrate. | Diagnostic test | – |
Primary outcome
To evaluate pulmonary thrombus burden
Time frame: 24 months
Authors will evaluate if a pulmonary embolus was originated prior or subsequent to a traumatic event. However, they will evaluate the dimension of the thrombus, and the quantity of fibrinogen present in the thrombus, from pulmonary vessels sections. The tissues samples will be fixed in 10% neutral buffered formalin and embedded in paraffin blocks, and stained with hematoxylin and eosin stain for diagnosis. For inflammatory cellular infiltration and fibrosis, authors will attribute a score 0 for no increase, score 1, 2, or 3 for little, moderate, or high increase of cell content compared to adjacent tissue, respectively. For the extracellular matrix production, authors will attribute a score 0 for absence of collagen production, score 1 and 2 for 10-40% and 40-80% collagen fibers content compared to adjacent normal tissue, respectively, and finally score 3 for wound matrix indistinguishable from adjacent normal tissue.
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 26 Mar 2019.
- Derived from this study: PubMed 31703628Mansueto G, Costa D, Capasso E, Varavallo F, Brunitto G, Caserta R, Esposito S, Niola M, Sardu C, Marfella R, Napoli C, Paternoster M. The dating of thrombus organization in cases of pulmonary embolism: an autopsy study. BMC Cardiovasc Disord. 2019 Nov 8;19(1):250. doi: 10.1186/s12872-019-1219-8.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Pulmonary Embolism, run by University of Campania Luigi Vanvitelli.
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 2 inclusion and 2 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 26 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
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?
To evaluate pulmonary thrombus burden (time frame: 24 months). 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 NCT03887819, which also lists 1 linked publication.
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 26 Mar 2019.