RIPT Feasibility Trial

Study Overview
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Brief Summary
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The risk of venous thromboembolism (VTE) is very high in trauma patients, secondary to tissue injury, venous status from immobilization, and thrombophilia. As such, early initiation of VTE prophylaxis is essential in this population. The competing risks of life threatening hemorrhage and VTE need to be considered very carefully. Potential approaches to VTE prophylaxis include pharmacologic means, and mechanical devices. For patients unable to receive pharmacologic VTE prophylaxis, retrievable inferior vena cava filters (rIVCFs) may be placed until low molecular weight heparin (LMWH) can be initiated, as per guidelines such as Eastern Association for the Surgery of Trauma The investigators propose a feasibility study to determine whether or not our center can insert rIVCFs in at-risk trauma patients expeditiously enough to cause a meaningful reduction in the time they are left unprotected to PE.

Detailed Description
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The risk of venous thromboembolism (VTE) is very high in trauma patients, secondary to tissue injury, venous status from immobilization, and thrombophilia. As such, early initiation of VTE prophylaxis is essential in this population. The competing risks of life threatening hemorrhage and VTE need to be considered very carefully. Potential approaches to VTE prophylaxis include pharmacologic means, and mechanical devices. For patients unable to receive pharmacologic VTE prophylaxis, retrievable inferior vena cava filters (rIVCFs) may be placed until low molecular weight heparin (LMWH) can be initiated. The need for mechanical VTE prophylaxis in patients unable to receive pharmacologic therapy is underscored by Geerts and colleagues' prospective study of trauma patients who did not receive anticoagulation. In their study, 58% of their 349 trauma patients sustained deep venous thromboses (DVT). [Geerts et a., 1994] Furthermore, a confirmed or clinically suspected pulmonary embolus (PE) was identified in an additional 5% of patients. Importantly, this study excluded patients who died during the first 5 days of admission. However, the highest risk of VTE occurs in the first 4 days after admission and many advocate early insertion of rIVCF [Owings et al. 1997, O'Malley et al. 1990, Carlin et al. 2002, Haut et al. 2014]. Coincidentally, VTE prophylaxis is often withheld pending repeat neurologic imaging and / or surgical intervention. Current guidelines on the use of rIVCFs are contradictory. The Eastern Association for the Surgery of Trauma's (EAST) practice management guideline suggests the use of rIVCFs are advisable in the very-high-risk trauma patients. Such patients are defined as the those who cannot receive anticoagulation because of increased bleeding risk and have sustained injuries preventing mobilization such as: i) severe closed head injury (GCS < 8) ii) incomplete spinal cord injury with paraplegia or quadriplegia iii) complex pelvic fracture with associated long bone fractures iv) multiple long bone fractures [Rogers et al 2002]. Contrasting this, the American College of Chest Physicians sated in their 2012 Guideline, that there is no role for rIVCFs in primary VTE prevention. [Gould et al. 2012] Reflecting this lack of consensus in guidelines, there is practice variability among major trauma centres. In an American based survey study of 131 Trauma Directors, LMWH was the preferred method for VTE prophylaxis in over half (51%) of the responders, followed by intermittent pneumatic compression devices (IPCD, 42%), Foot pump (8%) Low Dose Heparin (LDH, 7%) and rIVCFs (1%). In patients with contraindications to pharmacologic prophylaxis, the favoured approach for VTE Prophylaxis is IPCD (80%) followed by rIVCF (16%) and foot pump (9%). [Knudson et al. 2004] More work is needed to improve our understanding of the optimal role for rIVCFs, particularly considering recent advances in, and physician experience with rIVCF technology. One of the most cited concerns with the use of rIVCF in trauma patients is the low reported retrieval rates ranging from 21-35% of patients. [Kirilcuk et al. 2005, Antevil et al. 2006, Karmy-Jones et al., 2007] The need for VTE prophylaxis in trauma patients is usually temporary, and long term filter use is associated with an increased VTE risk, which was demonstrated in the PREPIC-1 trial and the 8-year follow up study examining the use of permanent IVCF in non-trauma patients with DVT for PE prevention [Decousus et al. 1998, PREPIC Study Group, 2005]. Of note, these trials were examining the role of rIVCF in patients for secondary prophylaxis in at risk patients with known VTE disease. The low retrieval rates of rIVCFs that have been reported in the Unites States are not a problem in our Canadian Lead Trauma Centre. We recently demonstrated a 97% retrieval rate in trauma patients surviving to discharge. [Leeper et al. 2015] We advocate a trial of early rIVCF use followed by prompt removal once medical prophylaxis is safe. There is a paucity of data regarding the use of rIVCFs in the Canadian setting, and our group is currently surveying Canadian trauma directors to improve our understanding of current practice. Despite the current deficiency of evidence, many Level 1 North American Trauma centres use rIVCF for primary VTE prophylaxis in their at risk trauma patients, as per EAST guidelines. In a recent meta-analysis by Haut et al. that reviewed 8 studies, they identified a reduction in PE incidence with rIVCF use, but concluded that further studies are required. [Haut et al. 2014] The investigators propose a feasibility study to determine whether or not our center can insert rIVCFs in at-risk trauma patients expeditiously enough to cause a meaningful reduction in the time they are left unprotected to PE.

Official Title
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Retrievable Inferior Vena Cava Filter for Primary Pulmonary Embolism Prophylaxis in At-Risk Trauma Patients: RIPT Feasibility Trial

Conditions
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Trauma, Pulmonary Embolism, Venous Thromboembolism

Intervention / Treatment
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* Device: Cook 'Celect' retrievable inferior vena cava filter


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: consecutive age adult trauma patients who are: Deemed unable to receive medial VTE prophylaxis within 72 hours post injury based on traumatologists' suspicion of increased bleeding risk, peri-spinal cord bleeding risk, or need for multiple surgical interventions. AND have at-least on of the following high risk VTE injuries as per EAST Guidelines: severe closed head injury (GCS 8 or less upon presentation) incomplete spinal cord injury with paraplegia or quadriplegia complex pelvic fracture with associated long bone fracture(s) multiple long bone fractures Exclusion Criteria: Patients not expected to survive for at least 72 hours post trauma Patients with known uncorrectable coagulopathy Patients known to be unable to receive a rIVC filter as part of this trial (for anatomical reasons or standard contraindication for device insertion) Known active venous thromboembolic disease Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rIVCF<br>Randomized to receive insertion of retrievable inferior vena cava filter until chemical anticoagulation can be safely administered. | Device: Cook 'Celect' retrievable inferior vena cava filter<br>* Cook 'Celect' device will be deployed If randomized to rIVCF insertion<br>|
| No Intervention: Standard Care<br>Randomized to not receive insertion of retrievable inferior vena cava filter. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time left unprotected to venous thromboembolism | time left unprotected to pulmonary embolism two weeks post arrival to hospital defined as: time point from arrival to LHSC to two weeks after, measured in hours where-in patient either has no rIVCF in situ, or has no regular low molecular weight heparin (LMWH) on board. missed doses of LMWH > 2 hours within planned administration time will count toward primary outcome. If LMWH is held for operative intervention, time left held > 24 hours post previous dose will count toward the primary outcome. | two weeks post trauma | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Venous Thromboembolism | 1. Incidence of symptomatic/clinically impactful pulmonary embolism (as defined by result of computed tomography pulmonary angiogram, autopsy, or ventilation perfusion scan, reported by a radiologist and ordered at the discretion of the MRP on clinical grounds. | in hospital (up to one year) | 
| Mortality | in hospital death | In Hospital (up to one year) | 
| Filter Feasibility Outcome: Time to filter insertion | a) time to filter insertion (defined as time from arrival to London Health Sciences Cente, to time of insertion of rIVCF as documented on the procedure note) b) time to filter removal (defined as time from rIVCF insertion, to removal) c) filter retrieval rate (percentage of patients who receive rIVCF who have rIVCF extraction, will track all patients through follow-up in Trauma Clinic upon discharge if they still have their devices in-situ) | hours to weeks, up to one year | 
| Filter Feasibility Outcome: Time to filter removal | b) time to filter removal (defined as time from rIVCF insertion, to removal) | hours to weeks, up to one year | 
| Filter Feasibility Outcome: Filter retrieval rate | c) filter retrieval rate (percentage of patients who receive rIVCF who have rIVCF extraction, will track all patients through follow-up in Trauma Clinic upon discharge if they still have their devices in-situ) | hours to weeks, up to one year | 
| Rates of worsening intracranial bleed | 5) rates of worsening intracranial haemorrhage within patients: Defined as the change in cubic volume of the documented hematoma found in serial computed tomography investigations (if done so as part of routine care) | up to 2 weeks |