Pulmonary Embolism
Conditions
Keywords
Venous thrombosis, pulmonary embolism, vena cava, inferior, vena cava filters, venous thromboembolism
Brief summary
This prospective, multicenter, double-arm clinical study further evaluated the safety and effectiveness of Cook's commercially available inferior vena cava (IVC) filters (specifically, the Günther Tulip® Vena Cava Filter and Cook Celect® Vena Cava Filters) in patients in need of temporary or permanent IVC filter placement for the prevention of pulmonary embolism (PE).
Interventions
DEVICEGünther Tulip® Vena Cava Filter
Temporary or permanent filter placement for the prevention of pulmonary embolism
DEVICECook Celect® Vena Cava Filters
Temporary or permanent filter placement for the prevention of pulmonary embolism
Sponsors
Cook Research Incorporated
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Requires temporary or permanent IVC filter placement for the prevention of PE
Exclusion criteria
* Less than 18 years of age * Known hypersensitivity or contraindication to contrast medium that cannot be adequately premedicated * Known allergy or sensitivity to cobalt, chromium, or nickel * Pregnant or planning to become pregnant in the next 12 months * Patient refuses blood transfusions * At risk of septic embolism * Medical condition or disorder that would limit life expectancy to less than 12 months or that may cause noncompliance with the protocol or confound the data analysis * Existing IVC filter * Duplicate IVC * Anatomy that would prevent safe filter placement (e.g., condition of access vessels) * IVC diameter \> 30 mm or \< 15 mm
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Supplemental Analysis to the Safety Endpoint: The Number of Participants With 12-month Freedom From Major Adverse Events (MAEs). | 12 months | MAEs were defined as clinical perforation, clinical migration, clinical fracture, embolization of the filter or filter fragments to the heart or lungs, IVC thrombotic occlusion, new symptomatic DVT while the filter is indwelling, access site complications with clinical sequelae, and procedure-/device-related death. A filter retrieval is considered a successful safety result through 12 months, regardless of when the retrieval occurred. |
| The Number of Participants With Technical Placement Success and With 12-month Freedom From New Symptomatic Pulmonary Embolism (PE) While a Filter is Indwelling. | 12 months | The protocol defined technical placement success as: deployment of filter in a location suitable to provide sufficient mechanical protection against PE with no filter deformation, fracture, premature release, or clinical migration (caudal or cranial movement of a filter resulting in a surgical or endovascular intervention). |
| The Rate of 12-month Freedom From Major Adverse Events (MAEs) | 12 months | MAEs were defined as clinical perforation, clinical migration, clinical fracture, embolization of the filter or filter fragments to the heart or lungs, IVC thrombotic occlusion, new symptomatic DVT while the filter is indwelling, access site complications with clinical sequelae, and procedure-/device-related death. Clinical perforation - Protrusion of filter legs through the wall of the IVC causing hemorrhage or hematoma or touching, impressing, or perforating another organ. Documented using CT. Clinical migration - Caudal or cranial movement of a filter resulting in surgical or endovascular intervention. Clinical fracture - A loss of structural integrity (breakage or separation) of the filter identified by imaging and associated with clinical sequelae and/or requiring intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Freedom From Grade 2 or Grade 3 Filter Leg Interaction With IVC, Filter Migration, Filter Fracture, and Filter Embolization at 12-month. | 12 months | Filter interaction with IVC is defined as : Grade 2: Filter strut is entirely outside of the IVC lumen and within the retroperitoneum as evidenced by a halo of retroperitoneal fat around axially viewed strut. Grade 3: Filter strut is touching, impressing, or perforating another organ (e.g., liver, bowel, aorta, psoas muscle, vertebral body, lymph nodes). Filter migration : Change in filter position compared to its deployed position (cranial or caudal). Filter fracture : Any loss of structural integrity (breakage or separation) of the filter identified by imaging or autopsy. Documented by imaging or at autopsy. Filter embolization : Post-placement movement of the filter or its components to a distant anatomic site completely out of the target zone (i.e., heart/lungs). Documented by imaging or autopsy. |
| Rate of Technical Placement Success and 12-month Freedom From New Symptomatic PE While Filter is Indwelling | 12 months | Rate of technical placement success and 12-month freedom from new symptomatic PE while a filter is indwelling for the combined patient population (i.e., the Celect and Günther Tulip strata). The protocol defined technical placement success as: deployment of filter in a location suitable to provide sufficient mechanical protection against PE with no filter deformation, fracture, premature release, or clinical migration (caudal or cranial movement of a filter resulting in a surgical or endovascular intervention). |
| Rate of 12-month Freedom From Major Adverse Events for the Combined Patient Population (i.e., the Celect and Günther Tulip Strata) | 12 months | MAEs were defined as clinical perforation, clinical migration, clinical fracture, embolization of the filter or filter fragments to the heart or lungs, IVC thrombotic occlusion, new symptomatic DVT while the filter is indwelling, access site complications with clinical sequelae, and procedure-/device-related death. Clinical perforation - Protrusion of filter legs through the wall of the IVC causing hemorrhage or hematoma or touching, impressing, or perforating another organ. Documented using CT. Clinical migration - Caudal or cranial movement of a filter resulting in surgical or endovascular intervention. Clinical fracture - A loss of structural integrity (breakage or separation) of the filter identified by imaging and associated with clinical sequelae and/or requiring intervention. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Filter Retrieval Rate | 2 years | The filters may be retrieved if clinically indicated. The IVC filter and IVC were assessed on imaging before a retrieval attempt. (The filter retrieval rate= the total number of filter retrieved / the total number of filter retrieval attempted) |
Countries
Australia, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Günther Tulip® Vena Cava Filter Günther Tulip® Vena Cava Filter
Günther Tulip® Vena Cava Filter: Temporary or permanent filter placement for the prevention of pulmonary embolism | 149 |
| Cook Celect® Vena Cava Filters Cook Celect® Vena Cava Filters
Cook Celect® Vena Cava Filters: Temporary or permanent filter placement for the prevention of pulmonary embolism | 324 |
| Total | 473 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 28 | 45 |
| Overall Study | Lost to Follow-up | 9 | 20 |
| Overall Study | Other endpoint | 2 | 19 |
| Overall Study | Withdrawal by Subject | 5 | 17 |
Baseline characteristics
| Characteristic | Günther Tulip® Vena Cava Filter | Cook Celect® Vena Cava Filters | Total |
|---|---|---|---|
| Age, Continuous | 61.9 years STANDARD_DEVIATION 15.4 | 60.7 years STANDARD_DEVIATION 16.4 | 61.1 years STANDARD_DEVIATION 16.1 |
| Body Mass Index( BMI) | 31.3 kg/m^2 STANDARD_DEVIATION 8.2 | 30.2 kg/m^2 STANDARD_DEVIATION 7.6 | 30.6 kg/m^2 STANDARD_DEVIATION 7.8 |
| Race/Ethnicity, Customized Asian | 0 Participants | 5 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian/White | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 17 Participants | 40 Participants | 57 Participants |
| Race/Ethnicity, Customized Black/Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 12 Participants | 31 Participants | 43 Participants |
| Race/Ethnicity, Customized Hispanic or Latino/White | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 120 Participants | 244 Participants | 364 Participants |
| Sex: Female, Male Female | 62 Participants | 140 Participants | 202 Participants |
| Sex: Female, Male Male | 87 Participants | 184 Participants | 271 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 45 / 324 | 28 / 149 |
| other Total, other adverse events | 0 / 324 | 0 / 149 |
| serious Total, serious adverse events | 76 / 324 | 43 / 149 |
Outcome results
Primary
Supplemental Analysis to the Safety Endpoint: The Number of Participants With 12-month Freedom From Major Adverse Events (MAEs).
MAEs were defined as clinical perforation, clinical migration, clinical fracture, embolization of the filter or filter fragments to the heart or lungs, IVC thrombotic occlusion, new symptomatic DVT while the filter is indwelling, access site complications with clinical sequelae, and procedure-/device-related death. A filter retrieval is considered a successful safety result through 12 months, regardless of when the retrieval occurred.
Time frame: 12 months
Population: The hypothesis was only tested for patients receiving Celect filters, in accordance with the protocol.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cook Celect® Vena Cava Filters | Supplemental Analysis to the Safety Endpoint: The Number of Participants With 12-month Freedom From Major Adverse Events (MAEs). | 281 Participants |
Comparison: Null Hypothesis: The 12-month freedom from MAE, π, does not meet the performance goal (80%).p-value: 0.00195% CI: [82.5, 90.2]One-tailed exact binomial test
Primary
The Number of Participants With Technical Placement Success and With 12-month Freedom From New Symptomatic Pulmonary Embolism (PE) While a Filter is Indwelling.
The protocol defined technical placement success as: deployment of filter in a location suitable to provide sufficient mechanical protection against PE with no filter deformation, fracture, premature release, or clinical migration (caudal or cranial movement of a filter resulting in a surgical or endovascular intervention).
Time frame: 12 months
Population: The hypothesis was tested only for patients receiving Celect filters, in accordance with the study protocol.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cook Celect® Vena Cava Filters | The Number of Participants With Technical Placement Success and With 12-month Freedom From New Symptomatic Pulmonary Embolism (PE) While a Filter is Indwelling. | 317 Participants |
Comparison: Null Hypothesis: The rate of technical placement success and 12-month freedom from new symptomatic PE while a filter is indwelling, π, does not meet the performance goal (90%).p-value: <0.000195% CI: [95.6, 99.1]One-tailed Exact binomial test
Primary
The Rate of 12-month Freedom From Major Adverse Events (MAEs)
MAEs were defined as clinical perforation, clinical migration, clinical fracture, embolization of the filter or filter fragments to the heart or lungs, IVC thrombotic occlusion, new symptomatic DVT while the filter is indwelling, access site complications with clinical sequelae, and procedure-/device-related death. Clinical perforation - Protrusion of filter legs through the wall of the IVC causing hemorrhage or hematoma or touching, impressing, or perforating another organ. Documented using CT. Clinical migration - Caudal or cranial movement of a filter resulting in surgical or endovascular intervention. Clinical fracture - A loss of structural integrity (breakage or separation) of the filter identified by imaging and associated with clinical sequelae and/or requiring intervention.
Time frame: 12 months
Population: The CIP defined methodology for analysis of the primary endpoint relied on Kaplan-Meier estimation. However, a large number of patients were censored (n=235), primarily due to filter retrieval (n=204).~The hypothesis was tested only for patients receiving Celect filters, in accordance with the study protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cook Celect® Vena Cava Filters | The Rate of 12-month Freedom From Major Adverse Events (MAEs) | 81.5 Rate of Freedom from MAE (%) | Standard Error 4.5 |
Comparison: the null hypotheses is: H0: S(t) ≤ 80%(Performance Goal) where,~* t is time through 12 months~* S(t) is the true rate of freedom from major adverse events at time t.p-value: 0.36995% CI: [72.6, 90.4]Z-statistic
Secondary
Number of Participants With Freedom From Grade 2 or Grade 3 Filter Leg Interaction With IVC, Filter Migration, Filter Fracture, and Filter Embolization at 12-month.
Filter interaction with IVC is defined as : Grade 2: Filter strut is entirely outside of the IVC lumen and within the retroperitoneum as evidenced by a halo of retroperitoneal fat around axially viewed strut. Grade 3: Filter strut is touching, impressing, or perforating another organ (e.g., liver, bowel, aorta, psoas muscle, vertebral body, lymph nodes). Filter migration : Change in filter position compared to its deployed position (cranial or caudal). Filter fracture : Any loss of structural integrity (breakage or separation) of the filter identified by imaging or autopsy. Documented by imaging or at autopsy. Filter embolization : Post-placement movement of the filter or its components to a distant anatomic site completely out of the target zone (i.e., heart/lungs). Documented by imaging or autopsy.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cook Celect® Vena Cava Filters | Number of Participants With Freedom From Grade 2 or Grade 3 Filter Leg Interaction With IVC, Filter Migration, Filter Fracture, and Filter Embolization at 12-month. | 274 Participants |
| Günther Tulip® Vena Cava Filter | Number of Participants With Freedom From Grade 2 or Grade 3 Filter Leg Interaction With IVC, Filter Migration, Filter Fracture, and Filter Embolization at 12-month. | 131 Participants |
| Total | Number of Participants With Freedom From Grade 2 or Grade 3 Filter Leg Interaction With IVC, Filter Migration, Filter Fracture, and Filter Embolization at 12-month. | 405 Participants |
Secondary
Rate of 12-month Freedom From Major Adverse Events for the Combined Patient Population (i.e., the Celect and Günther Tulip Strata)
MAEs were defined as clinical perforation, clinical migration, clinical fracture, embolization of the filter or filter fragments to the heart or lungs, IVC thrombotic occlusion, new symptomatic DVT while the filter is indwelling, access site complications with clinical sequelae, and procedure-/device-related death. Clinical perforation - Protrusion of filter legs through the wall of the IVC causing hemorrhage or hematoma or touching, impressing, or perforating another organ. Documented using CT. Clinical migration - Caudal or cranial movement of a filter resulting in surgical or endovascular intervention. Clinical fracture - A loss of structural integrity (breakage or separation) of the filter identified by imaging and associated with clinical sequelae and/or requiring intervention.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cook Celect® Vena Cava Filters | Rate of 12-month Freedom From Major Adverse Events for the Combined Patient Population (i.e., the Celect and Günther Tulip Strata) | 281 Participants |
| Günther Tulip® Vena Cava Filter | Rate of 12-month Freedom From Major Adverse Events for the Combined Patient Population (i.e., the Celect and Günther Tulip Strata) | 135 Participants |
| Total | Rate of 12-month Freedom From Major Adverse Events for the Combined Patient Population (i.e., the Celect and Günther Tulip Strata) | 416 Participants |
Secondary
Rate of Technical Placement Success and 12-month Freedom From New Symptomatic PE While Filter is Indwelling
Rate of technical placement success and 12-month freedom from new symptomatic PE while a filter is indwelling for the combined patient population (i.e., the Celect and Günther Tulip strata). The protocol defined technical placement success as: deployment of filter in a location suitable to provide sufficient mechanical protection against PE with no filter deformation, fracture, premature release, or clinical migration (caudal or cranial movement of a filter resulting in a surgical or endovascular intervention).
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cook Celect® Vena Cava Filters | Rate of Technical Placement Success and 12-month Freedom From New Symptomatic PE While Filter is Indwelling | 317 Participants |
| Günther Tulip® Vena Cava Filter | Rate of Technical Placement Success and 12-month Freedom From New Symptomatic PE While Filter is Indwelling | 147 Participants |
| Total | Rate of Technical Placement Success and 12-month Freedom From New Symptomatic PE While Filter is Indwelling | 464 Participants |
Other Pre-specified
Filter Retrieval Rate
The filters may be retrieved if clinically indicated. The IVC filter and IVC were assessed on imaging before a retrieval attempt. (The filter retrieval rate= the total number of filter retrieved / the total number of filter retrieval attempted)
Time frame: 2 years
Population: Patients with filter retrieval attempted
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cook Celect® Vena Cava Filters | Filter Retrieval Rate | 219 Participants |
| Günther Tulip® Vena Cava Filter | Filter Retrieval Rate | 99 Participants |
| Total | Filter Retrieval Rate | 318 Participants |