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Pulmonary EmbolismNCT03887819

Pulmonary Embolism: an Autopsy Study

An observational study of Pulmonary Embolism, run by University of Campania Luigi Vanvitelli.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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.

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.

  1. 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.

  1. First posted25 Mar 2019
  2. Study start1 Jan 2015
  3. Primary completion1 Jun 2018
  4. Study completion1 Jan 2019

Resources

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
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

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.

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