Clinical trial NCT02438462: Soluble Fibrin for Diagnosing Pulmonary Embolism
Official title: Evaluation of Performances of Soluble Fibrin Assay for Diagnosing Pulmonary Embolism
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pulmonary Embolism (PE)
Keywords: Pulmonary Embolism
Soluble Fibrin
D-Dimers
Clinical Probability Score
Imaging
Lead sponsor: Diagnostica Stago R&D
Sponsor class: INDUSTRY
Collaborators: name: European Georges Pompidou Hospital
First posted: 2015-05-08
Enrollment: 480
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Outpatients from Emergency or Respiratory and Intensive Care Medicine Units, in a French Hospital.

Brief summary: The purpose of the study is to evaluate the performances of Soluble Fibrin for diagnosing Pulmonary Embolism. Secondary objective is to compare the diagnostic performances of the Soluble Fibrin Assay and the D-Dimer test.

Detailed description: Rationale. Pulmonary embolism (PE) is a major public health problem. D-dimer (D-Di) assay is useful to exclude the PE but not specific, requiring irradiating and expensive imaging tests. Preliminary results suggest that the Soluble Fibrin (SF) assay has a sensitivity comparable to the D-Di one, but a higher specificity and thus would limit the use of imaging tests.

Main objective. To compute the area under the ROC curve of the Soluble Fibrin assay for the diagnosis of PE and to assess the other diagnostic characteristics of the SF assay.

Patients. Inclusion criteria: patients 18 years or older, referred to the Emergency or Respiratory and Intensive Care Medicine Units, for clinically suspected of PE.

Exclusion criteria: pregnancy, contraindication to iodinated contrast media, anticoagulant drug at curative doses, patients with suspected PE during hospitalization and those for which the three month-follow up is impossible.

The protocol was approved by the Ethics Committee on March 2015. The study will be conducted in compliance with French regulations after ethics approval.

Reference algorithm. PE has to be confirmed or excluded by the reference algorithm combining clinical probability, D-Dimer, imaging tests and three month-follow up. Plasma D-dimer (D-Di) is measured in case of low clinical probability. Helical computed tomography (CT) is performed in case of either high clinical probability or positive D-dimer. Lower limb venous compression ultrasonography (US) is done only in case of negative CT in a patient with a high clinical probability. Patients will be classified in two groups, as having or not having PE on predefined criteria according to the recent guidelines of the European Society of Cardiology by physicians who will be unaware of the SF assay result.

SF Assays. Soluble fibrin is measured by one site, using prototype assays, on both citrated and heparinized blood samples taken at baseline. Staff in charge of the assays are not aware of the clinical and diagnosis decisions.

Statistical Analysis of results. It will be performed independently by the Clinical Research Unit of Georges Pompidou European Hospital. The ROC curve will be built, the area under the curve will be calculated with its confidence interval. The most suitable threshold will be determined from the curve. Then the diagnostic performances of SF assay will be calculated according to the usual calculations.

Number of participants required. Taking into account an estimated area of 0.9 to 0.95 on preliminary data, the inclusion of 500 patients with suspected PE will allow calculation of the area under the ROC curve with an accuracy of 5%. This number will also allow calculation of the diagnostic performances of the SF assay with sufficient accuracy.

Duration of the study. The study period is three months for each patient, the total duration of the study is 28 months.

Eligibility criteria: Inclusion Criteria:

* patients are aged 18 years or older,
* outpatients from Emergency or Respiratory and Intensive Care Medicine Units,
* clinically suspected of PE

Exclusion Criteria:

* pregnant women,
* patients with contraindication to iodinated contrast media,
* patients treated with anticoagulants at curative doses,
* patients with suspected PE during hospitalization
* patients for which the three month-follow up is impossible.

Primary outcomes:
measure: Area under the ROC curve of the Soluble Fibrin for the diagnosis of PE
timeFrame: 28 months
Secondary outcomes:
measure: Threshold of the Soluble Fibrin assays for the diagnosis of PE
timeFrame: 28 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Georges Pompidou European Hospital
Study officials:
affiliation: Georges Pompidou European Hospital
name: Guy Meyer, Ph D
role: PRINCIPAL_INVESTIGATOR
affiliation: Diagnostica Stago R&D
name: Geneviève Contant, Ph D
role: STUDY_DIRECTOR
References:
citation: Roy PM, Colombet I, Durieux P, Chatellier G, Sors H, Meyer G. Systematic review and meta-analysis of strategies for the diagnosis of suspected pulmonary embolism. BMJ. 2005 Jul 30;331(7511):259. doi: 10.1136/bmj.331.7511.259.
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