IMPRoving Outcomes in Vascular DisEase- Aortic Dissection

Study Overview
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Brief Summary
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The goal of this clinical trial is to determine whether an upfront invasive strategy of TEVAR plus medical therapy reduces the occurrence of a composite endpoint of all-cause death or major aortic complications compared to an upfront conservative strategy of medical therapy with surveillance for deterioration in patients with uncomplicated type B aortic dissection.

Detailed Description
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The study will be a prospective, pragmatic, randomized clinical trial of the comparative effectiveness of an initial strategy for the treatment of uncomplicated type B aortic dissection (uTBAD). Patients with uTBAD and no prior history of aortic intervention will be randomized within 48 hours to 6 weeks after index admission to one of the two initial strategies. Follow-up will be ascertained via a centralized call center and ascertainment of medical records, as well as remote blood pressure monitoring. Recommendations regarding medical therapy will be made to enrolling centers and feedback on the quality of medical care given, however, all subsequent care, with the exception of aortic interventions, will be at the discretion of the responsible clinical care team. Aortic interventions will allowable only as per protocol.

Official Title
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IMPRoving Outcomes in Vascular DisEase- Aortic Dissection

Conditions
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Type B Aortic Dissection

Intervention / Treatment
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* Procedure: TEVAR
* Other: Guideline directed medical therapy and surveillance of dissection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 21 years Stanford type B aortic dissection not involving the aorta at or proximal to the innominate artery, without rupture and/or malperfusion (renal, mesenteric, or extremity) Acuity: within 48 hours - 6 weeks of index admission Ability to provide written informed consent and comply with the protocol Exclusion Criteria: Ongoing systemic infection Pregnant or planning to become pregnant in the next 3 months Life expectancy related to non-aortic conditions < 2 years Unwilling or unable to comply with all study procedures including serial imaging follow-up Known patient history of genetic aortopathy Penetrating Aortic Ulcer and Intramural hematoma Iatrogenic (traumatic) aortic dissection Previous aortic dissection or aortic surgery Prior aortic aneurysmal disease

Ages Eligible for Study
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Minimum Age: 21 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Upfront TEVAR plus Medical Therapy<br>Participants randomized to upfront TEVAR will receive a commercially available device customized to their individual anatomical requirements. Stent-graft implantation will be performed either in the operating room with appropriate digital imaging equipment to allow fluoroscopic and trans-esophageal echo (TEE) guidance or the catheterization laboratory, angiographic suite (with digital angiographic equipment). | Procedure: TEVAR<br>* Thoracic endovascular aortic repair<br>Other: Guideline directed medical therapy and surveillance of dissection<br>* Routine clinical care with suggested antihypertensive therapy and cardiovascular risk factor reduction as per appropriate cardiovascular guidelines.<br>|
| Active Comparator: Medical Therapy with surveillance for deterioration<br>Participants randomized to upfront Medical Therapy with Surveillance for Deterioration will be treated per routine clinical care with suggested antihypertensive therapy and cardiovascular risk factor reduction as per appropriate cardiovascular guidelines. | Other: Guideline directed medical therapy and surveillance of dissection<br>* Routine clinical care with suggested antihypertensive therapy and cardiovascular risk factor reduction as per appropriate cardiovascular guidelines.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause death or major aortic complications (MAC) | The primary endpoint is a composite of all-cause death or major aortic complications (MAC). MACs are defined as: Aortic rupture Malperfusion, New aortic tear requiring intervention, Retrograde aortic dissection, Dependence on outpatient dialysis (chronic) Major amputation (above ankle) Tracheostomy fistula formation (e.g., aorto-esophageal, aorto-tracheal) Spinal Cord Ischemia with paralysis or paresis (power 0-2) Stroke modified Rankin Scale 2-5 AD-related intervention in either group defined as: Open TAA/TAAA Repair Fenestrated and/or Branched Endovascular Repair of TAAA Repeat TEVAR | Last follow-up timepoint. Differential follow-up with median of about 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life, as measured by the Abdominal Aortic Aneurysm Quality of Life questionnaire (AAAQol) | An adapted version of the AAAQol survey and the Short Form 6 will be used to assess general and aortic specific quality of life. The AAAQol questionnaire was specifically developed and validated on patients with abdominal aortic aneurysms and measures both the physical and emotional impact of either 1) having an abdominal aortic aneurysm or 2) having surgical or endovascular therapy for an abdominal aortic aneurysm. This metric has been shown to be valid and responsive in abdominal aortic aneurysm. While it has not been tested in aortic dissection, its questions assess the same domains shown to be significantly impacted in patients with aortic dissection. | Last follow-up timepoint. Differential follow-up with median of about 4 years | 
| Cumulative incidence of cardiovascular (CV) hospitalizations | CV hospitalization will be defined as hospitalization >/= 24 hours for any cardiovascular cause. | Last follow-up timepoint. Differential follow-up with median of about 4 years | 
| Mean number of cardiovascular (CV) hospitalizations | CV hospitalization will be defined as hospitalization >/= 24 hours for any cardiovascular cause. | Last follow-up timepoint. Differential follow-up with median of about 4 years | 
| Incidence of cardiovascular death | Death from any cardiovascular cause. | Last follow-up timepoint. Differential follow-up with median of about 4 years | 
| Incidence of all-cause mortality | Death from any case | Last follow-up timepoint. Differential follow-up with median of about 4 years | 
| Cumulative incidence of aortic-related hospitalizations | Aortic-related hospitalizations include hospitalizations for: aortic rupture, malperfusion, new aortic tear requiring intervention, retrograde aortic dissection, admission for BP or pain control despite adequate medical therapy, stroke, or intervention for AD, aortic interventions including open TAA/TAAA repair or fenestrated and/or branched endovascular repair of TAAA or repeat TEVAR in either group. | Last follow-up timepoint. Differential follow-up with median of about 4 years | 
| Mean number of aortic-related hospitalizations | Aortic-related hospitalizations include hospitalizations for: aortic rupture, malperfusion, new aortic tear requiring intervention, retrograde aortic dissection, admission for BP or pain control despite adequate medical therapy, stroke, or intervention for AD, aortic interventions including open TAA/TAAA repair or fenestrated and/or branched endovascular repair of TAAA or repeat TEVAR in either group. | Last follow-up timepoint. Differential follow-up with median of about 4 years | 
| Incidence of stroke | Defined as a focal neurological deficit that could be attributed to a vascular territory and lasted >24 hours or was associated with a new lesion on computed tomography scan or magnetic resonance imaging. | Last follow-up timepoint. Differential follow-up with median of about 4 years | 
| Incidence of paraplegia or paraparesis | Defined as including: 1) flaccid paraplegia (no lower extremity movement), or lower extremity movement without gravity, or lower extremity movement with gravity, or standing with assistance or walking with assistance (Tarlov scores 0-4). | Last follow-up timepoint. Differential follow-up with median of about 4 years | 
| Incidence of vascular access injury requiring surgical repair | Defined as any open surgical procedure to treat a vascular injury at the site of vascular access for a previous endovascular procedure. | Last follow-up timepoint. Differential follow-up with median of about 4 years | 
| Incidence of aortobronchial / aortoesophageal fistula | Defined as fistulous connection between the aorta and bronchus as confirmed by chest imaging or direct visualization (surgical or bronchoscopic). Aortoesophageal fistula is defined as a fistulous connection between the aorta and the esophagus as confirmed by chest imaging or direct visualization (surgical or endoscopically). | Last follow-up timepoint. Differential follow-up with median of about 4 years | 
| Incidence of retrograde type A dissection | Defined as any new ascending arch, or descending dissection contiguous with and proximal to the original presenting anatomy as confirmed by imaging. | Last follow-up timepoint. Differential follow-up with median of about 4 years | 
| Incidence of aortic-related death, including sudden cardiac deaths | Aortic-related death will be defined as death within 30 days of 1) diagnosis of aortic dissection 2) any aortic intervention or 3) ruptured aortic aneurysm. This endpoint includes sudden cardiac deaths. Sudden cardiac death will be defined as unexpected death with a preceding symptom duration of < 24 hours. | Last follow-up timepoint. Differential follow-up with median of about 4 years | 
| Incidence of aortic-related death, excluding sudden cardiac deaths | Aortic-related death will be defined as death within 30 days of 1) diagnosis of aortic dissection 2) any aortic intervention or 3) ruptured aortic aneurysm. This endpoint does not include sudden cardiac deaths. Sudden cardiac death will be defined as unexpected death with a preceding symptom duration of < 24 hours. | Last follow-up timepoint. Differential follow-up with median of about 4 years | 
| Number of days alive and out of the hospital | Defined as the number of days alive minus the number of days in the hospital over 4 years (primary analysis). | Last follow-up timepoint. Differential follow-up with median of about 4 years | 
| Incidence of secondary percutaneous interventions after TEVAR | Any secondary percutaneous intervention after TEVAR | Last follow-up timepoint. Differential follow-up with median of about 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TEVAR