Prospective Investigation of Pulmonary Embolism Diagnosis III

Prospective Investigation of Pulmonary Embolism Diagnosis III (PIOPED III)

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).

Study Overview

• Status: Completed
• Conditions: Lung Diseases; Pulmonary Embolism
• Intervention / Treatment: Procedure: Magnetic Resonance Angiography; Procedure: Magnetic Resonance Venography

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.

• Study Type: Observational
• Enrollment (Anticipated): 1256

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Hospital
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Divison of Lung Diseases, NHLBI
    • Rockville, Maryland, United States, 20852
      • Data Coordinating Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Medical Center
    • Pontiac, Michigan, United States, 48341
      • St. Joseph Mercy-Oakland
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University Medical Center
  • New York
    • New York, New York, United States, 10016
      • NYU Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

People with suspected acute pulmonary embolism will be recruited for this study.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Diagnosis or exclusion of pulmonary embolism in agreement with a reference standard	Measured within 36 to 48 hours of study entry

Collaborators and Investigators

• Sponsor: George Washington University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Sarah Fowler, PhD, George Washington University; Principal Investigator: Charles Hales, MD, Massachusetts General Hospital; Principal Investigator: Russell Hull, MBBS, MSc, University of Calgary; Principal Investigator: Kenneth Leeper, Jr., MD, Emory University; Principal Investigator: David Naidich, MD, NYU Langone Health; Principal Investigator: Daniel Sak, Do, St. Joseph Mercy Oakland; Study Chair: Paul D. Stein, MD, St. Joseph Mercy Oakland; Principal Investigator: John Weg, MD, University of Michigan at Ann Arbor; Principal Investigator: Pamela Woodard, MD, Washington University School of Medicine

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): September 1, 2008
• Study Completion: April 1, 2009

Study Registration Dates

• First Submitted: October 17, 2005
• First Submitted That Met QC Criteria: October 17, 2005
• First Posted (Estimate): October 19, 2005

Study Record Updates

• Last Update Posted (Estimate): August 20, 2013
• Last Update Submitted That Met QC Criteria: August 19, 2013
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Embolism and Thrombosis; Lung Diseases; Embolism; Pulmonary Embolism
• Other Study ID Numbers: 329; U01HL077155 (U.S. NIH Grant/Contract); U01HL077149 (U.S. NIH Grant/Contract); U01HL077150 (U.S. NIH Grant/Contract); U01HL077151 (U.S. NIH Grant/Contract); U01HL077153 (U.S. NIH Grant/Contract); U01HL077154 (U.S. NIH Grant/Contract); U01HL077358 (U.S. NIH Grant/Contract); U01HL081593 (U.S. NIH Grant/Contract); U01HL081594 (U.S. NIH Grant/Contract)