Soluble Fibrin for Diagnosing Pulmonary Embolism (SOFIE)

Diagnostica Stago

Status: Completed

Conditions: Pulmonary Embolism (PE)

Treatments: Other: Soluble Fibrin

Study type: Observational

Funder types: Other; Industry

Identifiers

NCT02438462

SOFIE 2015-A00094-45

Details and patient eligibility

About

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.

Full 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.

Enrollment: 480 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

480 participants in 2 patient groups

Group with PE

Description:

The criteria for confirmation of PE are: * PE on spiral computed tomography (CT) * proximal deep vein thrombosis on ultrasound (US) * thromboembolic events objectively confirmed during the follow up

Treatment:

Other: Soluble Fibrin

Group without PE

Description:

The criteria for exclusion of PE are: * low or moderate clinical probability and D-dimer ELISA \<0.50 µg/mL or \<10xage in patients older than 50 years and negative follow up * low and moderate clinical probability and negative CT and negative follow up * high clinical probability and negative CT, US and follow up.

Treatment:

Other: Soluble Fibrin