Clinical trial NCT00241826: Prospective Investigation of Pulmonary Embolism Diagnosis III
Official title: Prospective Investigation of Pulmonary Embolism Diagnosis III (PIOPED III)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Lung Diseases
Pulmonary Embolism
Lead sponsor: George Washington University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2005-10-19
Enrollment: 1256
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: People with suspected acute pulmonary embolism will be recruited for this study.

Brief summary: The purpose of this study is to determine the diagnostic accuracy of gadolinium-enhanced magnetic resonance angiography (Gd-MRA) of the pulmonary arteries in combination with magnetic resonance venography (MRV) of the veins of the thighs in patients with clinically suspected acute pulmonary embolism (PE).

Detailed description: BACKGROUND:

Prospective Investigation of Pulmonary Embolism Diagnosis III (PIOPED III) follows PIOPED I and PIOPED II. PIOPED I was a multicenter trial supported between 1983 and 1989 to evaluate the sensitivity and specificity of two major, widely used technologies, radionuclear imaging (ventilation-perfusion scanning) and pulmonary angiography, for the diagnosis of PE. PIOPED II was a multicenter trial conducted between 2000 and 2005 to determine the value of contrast-enhanced spiral computed tomography (spiral CT) for the diagnosis of acute PE.

In PIOPED II, among 7,284 patients with suspected acute PE, 18.6% had an elevated creatinine, 3.9% were allergic to iodinated contrast material, and 4.7% of women were pregnant. One or more of these relative contraindications to an imaging procedure that would expose the patient to ionizing radiation or iodinated contrast material was present in 24.4% of patients with suspected acute PE. Although patients with relative contraindications often take the risk of CT or digital subtraction angiography (DSA) because of the importance of having a definitive diagnosis, such patients could benefit from safer diagnostic testing with Gd-MRA/MRV if it is shown to be sufficiently accurate.

The purpose of this investigation is to determine the extent to which Gd-MRA/MRV can serve as a diagnostic test in patients with clinically suspected PE and thereby eliminate the need for iodinated contrast material or ionizing radiation in patients who have a relative contraindication to one of them. This is important because 24% of patients with suspected acute PE have a relative contraindication to diagnostic procedures that involve ionizing radiation or iodinated contrast material.

DESIGN NARRATIVE:

PIOPED III is a multicenter prospective investigation designed to determine the diagnostic accuracy of Gd-MRA of the pulmonary arteries in combination with MRV of the veins of the thighs in patients with clinically suspected acute PE. The diagnostic accuracy of Gd-MRA alone and in combination with MRV will be expressed as sensitivity, specificity, and likelihood ratio for positive and negative tests. The study design is a prospective study of consecutive patients incorporating standardized inclusion/exclusion criteria, complete ascertainment of patient characteristics and outcomes, uniform diagnostic criteria, and unbiased paired central readings of imaging studies. Over a period of 2 years, 1,256 patients with suspected acute PE will be recruited at clinical centers. Composite reference standards will be used to diagnose venous thromboembolism (VTE) and exclude PE. It is expected that 314 patients will have acute VTE and they will undergo Gd-MRA/MRV. It is expected that 942 patients will be shown not to have PE. From among this group, 314 patients will be randomly selected for the index test, Gd-MRA/MRV.

Eligibility criteria: Inclusion Criteria:

* Acute PE of diagnostic concern
* Informed consent
* Willing to undergo Gd-MRA/MRV

Exclusion Criteria:

* Any implanted ferromagnetic foreign body, including a ferromagnetic cerebral aneurysm clip or implanted electrical device/pump
* Dependency on a continuous connection to an external electrical device/pump (e.g., pacemaker, internal defibrillator, cochlear implant, nerve or bone stimulator implant, ICU appliance) and cardiac pacing wires
* Severe claustrophobia
* Severe shaking
* Inability to lie still for 30 minutes
* Pregnancy and nursing mothers
* Serum creatinine levels within range of normal at local center
* Sickle cell anemia, other hemoglobinopathies, and other hemolytic anemias
* Critical illness, shock or hypotension, hemodynamic instability, ventilatory support, chronic anticoagulation, inferior vena cava filter
* Documented episodes of ventricular fibrillation or sustained ventricular tachycardia within the past 24 hours
* Myocardial infarction within the past month
* History of allergy to gadolinium-containing contrast agents or to iodinated contrast media
* Current symptomatic asthma
* Clinical evidence of venous thrombosis of the upper extremity
* Prisoners
* Institutionalized or mentally handicapped patients
* Too large to fit in MRI unit

Primary outcomes:
measure: Diagnosis or exclusion of pulmonary embolism in agreement with a reference standard
timeFrame: Measured within 36 to 48 hours of study entry
Secondary outcomes:
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Bethesda
country: United States
facility: Divison of Lung Diseases, NHLBI
state: Maryland
city: Rockville
country: United States
facility: Data Coordinating Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Pontiac
country: United States
facility: St. Joseph Mercy-Oakland
state: Michigan
city: St. Louis
country: United States
facility: Washington University Medical Center
state: Missouri
city: New York
country: United States
facility: NYU Medical Center
state: New York
city: Calgary
country: Canada
facility: Foothills Hospital
state: Alberta
Study officials:
affiliation: George Washington University
name: Sarah Fowler, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: Charles Hales, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Calgary
name: Russell Hull, MBBS, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University
name: Kenneth Leeper, Jr., MD
role: PRINCIPAL_INVESTIGATOR
affiliation: NYU Langone Health
name: David Naidich, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Joseph Mercy Oakland
name: Daniel Sak, Do
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Joseph Mercy Oakland
name: Paul D. Stein, MD
role: STUDY_CHAIR
affiliation: University of Michigan at Ann Arbor
name: John Weg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Washington University School of Medicine
name: Pamela Woodard, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stein PD, Chenevert TL, Fowler SE, Goodman LR, Gottschalk A, Hales CA, Hull RD, Jablonski KA, Leeper KV Jr, Naidich DP, Sak DJ, Sostman HD, Tapson VF, Weg JG, Woodard PK; PIOPED III (Prospective Investigation of Pulmonary Embolism Diagnosis III) Investigators. Gadolinium-enhanced magnetic resonance angiography for pulmonary embolism: a multicenter prospective study (PIOPED III). Ann Intern Med. 2010 Apr 6;152(7):434-43, W142-3. doi: 10.7326/0003-4819-152-7-201004060-00008.