Clinical trial NCT00771303: Ruling Out Pulmonary Embolism During Pregnancy:a Multicenter Outcome Study
Official title: Ruling Out Pulmonary Embolism During Pregnancy:a Multicenter Outcome Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pulmonary Embolism
Deep Vein Thrombosis
Keywords: Pregnancy
Pulmonary embolism
MSCT
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
Collaborators: name: Swiss National Science Foundation
name: University Hospital, Brest
First posted: 2008-10-13
Enrollment: 402
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Pregnant women with suspected PE.

Brief summary: Venous thromboembolism (VTE) remains a major cause of maternal morbidity and mortality in developed countries. Objective diagnosis of pulmonary embolism (PE) and/or deep vein thrombosis (DVT) in pregnancy is crucial. Failure to identify PE or/or DVT will place the mother's life at risk, and unnecessary treatment will not only expose her to anticoagulants but will also label her as having had VTE. Thus, this diagnosis has serious implications for the management of her present pregnancy, and for other aspects of her life ranging from contraception to thromboprophylaxis in future pregnancies and hormone replacement therapy in later life. It is therefore critical that all women with symptoms or signs that suggest venous thromboembolism have appropriate investigation and diagnosis based on objective diagnostic tests.

The current diagnostic approach in suspected PE is based on sequential diagnostic tests: 1) assessment of clinical probability, 2) fibrin D-dimer measurement, 3) compression ultrasonography of lower limb veins and 4) multi-slice computed tomography (MSCT). However, physicians are reluctant to perform MSCT in pregnant women because of potential adverse effect of radiation exposure to the fetus. For this reason, ventilation/perfusion or perfusion-only lung scan has been the cornerstone of PE diagnosis in pregnant women. Indeed, perfusion lung scan was assumed to be associated with less radiation than computed tomography (CT). However, this technique is now widely abandoned in the usual diagnostic strategy of PE for the following reasons: it is not widely available; its interpretation may be difficult and the test may be inconclusive in the presence of other chest abnormalities. Moreover, recent data convincingly show that the radiation exposure associated with single-slice or multi-slice CT exposes the fetus to less radiation than perfusion lung scan.

However, the use of CT has never been adequately validated in pregnant women with clinically suspected PE. The investigators, therefore, plan to set up a prospective management study in which pregnant women with suspected PE will undergo a sequential diagnostic strategy based on 1) assessment of clinical probability 2) D-dimer measurement 3) compression ultrasonography, and 4) MSCT.

Nowadays, the overestimated fear of radiation exposure for the fetus leads to an irrational attitude and inadequate investigations in pregnant women with suspected PE, even though both European \[3, 4\] and North-American guidelines \[5\] suggest that only objective testing may accurately rule out the disease. The proposed study should lead to an increased awareness of the risks and benefits of appropriate imaging in pregnant women suspected of PE and should result in a more rational management of this under-studied patient group.

Detailed description: Venous thromboembolism (VTE) remains a major cause of maternal morbidity and mortality in developed countries. Objective diagnosis of pulmonary embolism (PE) and/or deep vein thrombosis (DVT) in pregnancy is crucial. Failure to identify PE or/or DVT will place the mother's life at risk, and unnecessary treatment will not only expose her to anticoagulants but will also label her as having had VTE. Thus, this diagnosis has serious implications for the management of her present pregnancy, and for other aspects of her life ranging from contraception to thromboprophylaxis in future pregnancies and hormone replacement therapy in later life. It is therefore critical that all women with symptoms or signs that suggest venous thromboembolism have appropriate investigation and diagnosis based on objective diagnostic tests.

Diagnosis of VTE on a clinical basis is unreliable, especially during pregnancy because leg swelling and mild dyspnea are frequent during normal pregnancy.

The current diagnostic approach in suspected PE is based on sequential diagnostic tests: 1) assessment of clinical probability, 2) fibrin D-dimer measurement, 3) compression ultrasonography of lower limb veins and 4) multi-slice computed tomography (MSCT). However, physicians are reluctant to perform MSCT in pregnant women because of potential adverse effect of radiation exposure to the fetus. For this reason, ventilation/perfusion or perfusion-only lung scan has been the cornerstone of PE diagnosis in pregnant women. Indeed, perfusion lung scan was assumed to be associated with less radiation than computed tomography (CT). However, this technique is now widely abandoned in the usual diagnostic strategy of PE for the following reasons: it is not widely available; its interpretation may be difficult and the test may be inconclusive in the presence of other chest abnormalities. Moreover, recent data convincingly show that the radiation exposure associated with single-slice or multi-slice CT exposes the fetus to less radiation than perfusion lung scan.

However, the use of CT has never been adequately validated in pregnant women with clinically suspected PE. We, therefore, plan to set up a prospective management study in which pregnant women with suspected PE will undergo a sequential diagnostic strategy based on 1) assessment of clinical probability 2) D-dimer measurement 3) compression ultrasonography, and 4) MSCT.

Nowadays, the overestimated fear of radiation exposure for the fetus leads to an irrational attitude and inadequate investigations in pregnant women with suspected PE, even though both European and North-American guidelines suggest that only objective testing may accurately rule out the disease. The proposed study should lead to an increased awareness of the risks and benefits of appropriate imaging in pregnant women suspected of PE and should result in a more rational management of this under-studied patient group.

Eligibility criteria: Inclusion Criteria:

* All pregnant patients with a clinical suspicion of acute PE will be included in the study, provided they correspond to the following diagnostic and exclusion criteria, and they have signed an informed consent form.

Exclusion Criteria:

* Age less than 18 years
* Absence of informed consent
* Patients allergic to contrast medium
* Impaired renal function (creatine clearance less than 30 ml/min as estimated by the Cockroft formula)
* Geographic inaccessibility for follow-up

Primary outcomes:
measure: Proportion of patients with a symptomatic thromboembolic event in the three month follow-up among those in whom PE was ruled out by the diagnostic strategy and who were left untreated by anticoagulants.
timeFrame: 3 months
Secondary outcomes:
measure: Efficacy of non invasive testing
timeFrame: 3 months
measure: Proportion of patients with a negative D-dimer result
timeFrame: 3 months
measure: Proportion of patients with a lower limb venous ultrasound showing a proximal DVT
timeFrame: 3 months
Other outcomes:
Locations:
city: Angers
country: France
facility: Pierre-Marie ROY
city: Brest
country: France
facility: Grégoire LE GAL
city: Clamart
country: France
facility: Florence PARENT
city: Montpellier
country: France
facility: Isabelle QUERE
city: Nîmes
country: France
facility: Jean-Christophe GRIS
city: Paris
country: France
facility: Guy MEYER
city: Pau
country: France
facility: Caroline BOHEC
city: Toulon
country: France
facility: Antoine ELIAS
city: Geneva
country: Switzerland
facility: Marc Righini
Study officials:
References: