Clinical trial NCT00368836: Breath Analysis Technique to Diagnose Pulmonary Embolism
Official title: Expired CO2/O2 Analysis to Diagnose Pulmonary Embolism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Pulmonary Embolism
Keywords: Capnography
Thromboembolism
Arthroplasty
D-dimer
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: WFD Ventures Incorporated
First posted: 2006-08-29
Enrollment: 475
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: A pulmonary embolism (PE) is a blockage in one of the arteries of the lungs, and is usually caused by a traveling blood clot. The D-dimer blood test is currently used to diagnose PEs, but it is not always accurate for individuals who have recently undergone surgery or who have inflammatory-provoking diseases. The purpose of this study is to evaluate the effectiveness of the Carboximeter, a new PE diagnostic device that measures carbon dioxide (CO2) and oxygen (O2) output, in individuals at risk for developing PEs.

Detailed description: PE is the second leading cause of sudden, unexpected death in the United States. In 90% of the cases, it is caused by deep vein thrombosis: a blood clot forms in a vein, travels through the bloodstream, and lodges in the lungs. PE symptoms vary, and can include cough, shortness of breath, chest pain, rapid breathing, or increased heart rate. Some medical procedures and diseases activate inflammation and blood coagulation, thereby making individuals more vulnerable to PE. Surgery, kidney dialysis, cancer, connective tissue diseases, infectious diseases, and being over 70 years old put individuals at increased risk for developing PEs. A common screening test for PE is the D-dimer blood test, which measures the level of a specific protein that is released following a PE. This test, however, has proven to be an unreliable diagnostic tool for individuals who are at high risk for PE. A more reliable diagnostic tool is needed. The Carboximeter is a new device that measures the ratio of CO2/O2 pressure in an individual's expired breath. By monitoring these components, researchers may be able to accurately diagnose PEs in high risk individuals. The purpose of this study is to evaluate the effectiveness of the Carboximeter at diagnosing PE in individuals at risk for developing PEs.

This study will be conducted in two phases. In Phase I, CO2/O2 ratio and D-dimer levels will be measured prior to and following orthopedic or cancer-related surgery in 100 individuals at risk for developing PEs. In Phase II, the same measurements will be carried out on 350 high risk individuals who are experiencing PE symptoms. These individuals will also undergo computed tomography (CT) angiography and venography, in which blood flow will be visualized using x-rays. A follow-up evaluation will occur 30 days later. If any participant from Phase I or II experiences a PE or a medical condition that affects their lungs, such as asthma or chronic obstructive pulmonary disease (COPD), researchers may schedule a follow-up evaluation to obtain repeat measurements.

Eligibility criteria: Phase I Inclusion Criteria:

* Experienced or is scheduled for at least one of the following:

  1. Hip or knee replacement surgery
  2. Hip or acetabular fracture surgery
  3. Pelvic fracture
  4. Decompression for spinal stenosis surgery
  5. Scoliosis corrective surgery
  6. Craniotomy surgery for brain tumor
  7. Surgery for any of the following cancers: bladder, colon (including caecum and rectum), kidney, ovary, pancreas, or uterus

Phase I Exclusion Criteria:

* Currently undergoing treatment for PE or has received treatment for PE in the 4 weeks prior to study entry
* Hospitalized for fewer than 2 days
* Anatomic abnormality that would prevent use of a mouthpiece
* Living situation that makes follow-up difficult (e.g., homeless, incarcerated)

Phase II Inclusion Criteria:

* Clinical suspicion of PE with signs or symptom suggestive of PE within 24 hours of presentation and at least one risk factor for PE, as defined under the criteria as outlined in this protocol
* CTA of pulmonary arteries ordered by clinical care providers
* 18 years or older or an emancipated 17 year old
* Written informed consent

Phase II Exclusion Criteria:

* Hemodynamic instability, including patients with a systolic blood pressure less than 90 mm Hg
* Severe respiratory distress or the inability to breathe room air without the sensation of severe dyspnea
* Pulse oximetry reading that declines more than 10% when exogenous oxygen is discontinued with accompanying worsening or new dyspnea
* Intubated
* Cannot breathe through the mouth owing to anatomic, physical or mental limitation
* No fixed address, no telephone number, are from out of town or have other reason to suspect difficulty with follow-up
* Incarceration
* Known active tuberculosis
* Prior PE or DVT with history of medical noncompliance with oral anticoagulation therapy based upon a history of unplanned subtherapeutic INR measurements (less than 1.5)
* Active PE within previous 6 months and currently under treatment with anticoagulation
* Pregnant
* Disallowed medications: treatment with any fibrinolytic agent within 48 hours prior to enrollment

Primary outcomes:
measure: Phase I: Percentage Change in the Postoperative End Tidal CO2/O2 Ratio and D-dimer Concentration Relative to the Preoperative Measurement
timeFrame: Pre-op measurement: the morning of surgery. Post-op measurement: the latter of postoperative day 3 or hospital discharge
measure: Phase II: Probability of Pulmonary Embolism Diagnosis by D-dimer Alone vs. D-Dimer Plus CO2/O2 for Pulmonary Embolism Diagnosed by CT Scan.
timeFrame: Measured at 45 days
Secondary outcomes:
Other outcomes:
Locations:
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
Study officials:
affiliation: Indiana University School of Medicine
name: Jefferey A. Kline, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kline JA, Hogg M. Measurement of expired carbon dioxide, oxygen and volume in conjunction with pretest probability estimation as a method to diagnose and exclude pulmonary venous thromboembolism. Clin Physiol Funct Imaging. 2006 Jul;26(4):212-9. doi: 10.1111/j.1475-097X.2006.00672.x.
citation: Kline JA, Watts J, Courtney D, Lee YY, Hwang S. Severe pulmonary embolism decreases plasma L-arginine. Eur Respir J. 2014 Mar;43(3):906-9. doi: 10.1183/09031936.00171913. Epub 2013 Nov 14. No abstract available.
citation: Kline JA, Hogg MM, Courtney DM, Miller CD, Jones AE, Smithline HA. D-dimer threshold increase with pretest probability unlikely for pulmonary embolism to decrease unnecessary computerized tomographic pulmonary angiography. J Thromb Haemost. 2012 Apr;10(4):572-81. doi: 10.1111/j.1538-7836.2012.04647.x.
citation: Kline JA, Hogg MM, Courtney DM, Miller CD, Jones AE, Smithline HA, Klekowski N, Lanier R. D-dimer and exhaled CO2/O2 to detect segmental pulmonary embolism in moderate-risk patients. Am J Respir Crit Care Med. 2010 Sep 1;182(5):669-75. doi: 10.1164/rccm.201001-0129OC. Epub 2010 May 6.