Pulmonary Embolism
Conditions
Keywords
Capnography, Thromboembolism, Arthroplasty, D-dimer
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.
Interventions
DEVICEBreathScreen PE
One minute of breath collection by tidal breathing into the BreathScreen PE and blood draw for D-dimer level
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
WFD Ventures Incorporated
Wake Forest University Health Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase I: Percentage Change in the Postoperative End Tidal CO2/O2 Ratio and D-dimer Concentration Relative to the Preoperative Measurement | Pre-op measurement: the morning of surgery. Post-op measurement: the latter of postoperative day 3 or hospital discharge | Median postoperative change in end tidal CO2/O2 ratio calculated as 100% \* \[(postoperative-preoperative)/(preoperative)\] |
| Phase II: Probability of Pulmonary Embolism Diagnosis by D-dimer Alone vs. D-Dimer Plus CO2/O2 for Pulmonary Embolism Diagnosed by CT Scan. | Measured at 45 days | D-dimer \> 499 ng/ml, etCO2/O2 \< 0.28, Pulmonary Embolism diagnosed by CT scan |
Countries
United States
Participant flow
Recruitment details
Phase I - subjects scheduled for elective surgery enrolled from January 2006-May 2006. Phase II - Hospitalized as well as Emergency Department patients were enrolled from February, 2007 to April, 2008
Participants by arm
| Arm | Count |
|---|---|
| Phase II Symptomatic population undergoing testing for pulmonary embolism. Blood samples were used to obtain D-dimer levels and breath samples were used to generate the BreathScreen PE CO2/O2 ratio. | 350 |
| Phase I Pre-op/Post op subjects undergoing surgery. Blood and breath samples were collected before and after surgery. Blood samples were used to obtain D-dimer levels and breath samples were used to generate the BreathScreen PE CO2/O2 ratio. | 125 |
| Total | 475 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Phase II | Protocol Violation | 2 |
| Phase II | Screen Failure | 1 |
| Phase II | unable to collect blood and/or breath | 17 |
| Phase II | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Phase II | Phase I | Total |
|---|---|---|---|
| Age, Continuous | 54.7 years STANDARD_DEVIATION 15.9 | 62 years STANDARD_DEVIATION 12 | 56.3 years STANDARD_DEVIATION 15.3 |
| Region of Enrollment United States | 350 participants | 125 participants | 475 participants |
| Sex: Female, Male Female | 212 Participants | 67 Participants | 279 Participants |
| Sex: Female, Male Male | 138 Participants | 58 Participants | 196 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 348 | 0 / 125 |
| serious Total, serious adverse events | 0 / 348 | 0 / 125 |
Outcome results
Primary
Phase II: Probability of Pulmonary Embolism Diagnosis by D-dimer Alone vs. D-Dimer Plus CO2/O2 for Pulmonary Embolism Diagnosed by CT Scan.
D-dimer \> 499 ng/ml, etCO2/O2 \< 0.28, Pulmonary Embolism diagnosed by CT scan
Time frame: Measured at 45 days
Population: Completed patients minus unrecoverable data (4) and indeterminate CT scan (2).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BreathScreen PE | Phase II: Probability of Pulmonary Embolism Diagnosis by D-dimer Alone vs. D-Dimer Plus CO2/O2 for Pulmonary Embolism Diagnosed by CT Scan. | 0.32 probability of PE diagnosis |
| D-dimer | Phase II: Probability of Pulmonary Embolism Diagnosis by D-dimer Alone vs. D-Dimer Plus CO2/O2 for Pulmonary Embolism Diagnosed by CT Scan. | 0.17 probability of PE diagnosis |
Primary
Phase I: Percentage Change in the Postoperative End Tidal CO2/O2 Ratio and D-dimer Concentration Relative to the Preoperative Measurement
Median postoperative change in end tidal CO2/O2 ratio calculated as 100% \* \[(postoperative-preoperative)/(preoperative)\]
Time frame: Pre-op measurement: the morning of surgery. Post-op measurement: the latter of postoperative day 3 or hospital discharge
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BreathScreen PE | Phase I: Percentage Change in the Postoperative End Tidal CO2/O2 Ratio and D-dimer Concentration Relative to the Preoperative Measurement | end tidal CO2/O2 ratio | 0 percent change |
| BreathScreen PE | Phase I: Percentage Change in the Postoperative End Tidal CO2/O2 Ratio and D-dimer Concentration Relative to the Preoperative Measurement | D-dimer concentration | 136 percent change |