IMPRoving Outcomes in Vascular DisEase- Aortic Dissection (IMPROVE-AD)

The University of Texas Health Science Center, Houston, State University of New York - Downstate Medical Center, Oregon Health and Science University, National Heart, Lung, and Blood Institute (NHLBI)

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.

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.

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).

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.

Routine clinical care with suggested antihypertensive therapy and cardiovascular risk factor reduction as per appropriate cardiovascular guidelines.

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

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.

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.

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.

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.

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).

Defined as any open surgical procedure to treat a vascular injury at the site of vascular access for a previous endovascular procedure.

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).

Defined as any new ascending arch, or descending dissection contiguous with and proximal to the original presenting anatomy as confirmed by imaging.

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.

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.

Defined as the number of days alive minus the number of days in the hospital over 4 years (primary analysis).

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

The Statistical and data analytic center (SDCC) will submit to the NHLBI data repository de-identified Limited Access Datasets (LADs) and associated documentation, for use by other investigators. The LADs and documentation will be submitted within 2 years after publication of the primary results manuscript. Documentation will include copies of the case report forms; a list of derived variables and the formulas used to create them; and a codebook providing for each variable the variable name, coding conventions, and distribution of values. It will also include a list of data modifications made when creating the LAD, and a copy of the informed consent template, so that future use of the data will be consistent with the consent provided by the study subjects.The goal is to make data available to other investigators while protecting the rights and privacy of the subjects who participated in the studies. The SDCC will anonymize the datasets.

The methods for restricting access will also need to be determined, either with password access and/or with executed Data Agreements. Related to the restricted use of data is the need to specify appropriately in informed consent forms that the study participant's de-identified data may be made available to other researchers.