# 2/2 IMPRroving Outcomes in Vascular DisEase - Aortic Dissection (IMPROVE-AD)

> **NIH NIH U24** · DUKE UNIVERSITY · 2024 · $721,106

## Abstract

This submission comprises two applications (Clinical and Statistical Data Coordinating Centers). We propose
to conduct a large (N=1,100), simple, pragmatic, superiority trial in the US - IMPROVE-AD – comparing a
strategy of medical therapy (MT) plus upfront thoracic endovascular aortic repair (TEVAR) to MT plus
surveillance for deterioration in patients with uncomplicated type B aortic dissection (uTBAD). Surveillance will
include clinically indicated TEVAR and/or open repair performed for deterioration during index hospitalization
or follow up. This is the first trial of this size designed to establish guidance on uTBAD management. The trial
leadership is comprised of an experienced group of investigators in a Clinical Coordination Center (CCC; Duke
Clinical Research Institute, Durham, NC, Baylor College of Medicine, Houston, TX, and University of
Washington, Seattle, WA) a Statistical and Data Coordination Center (SDCC; Duke Clinical Research Institute,
Durham, NC) and a diverse, Executive and Steering Committee of experts in the field representing clinicians,
trialists, and patient advocates. Aortic dissection (AD) is the most common fatal event involving the aorta
occurring in 5 to 30 cases per million of population resulting in 12,000 deaths in the US annually. Type B aortic
dissections involve the entire descending aorta. Based on evidence from the 1960s, the main strategy for
uTBAD is medical therapy with lifelong surveillance. This strategy has been shown to have poor long-term
outcome in 25-50% of patients (aortic related events). The emergence of TEVAR as a less invasive alternative
to open repair, however, has resulted in debate over the use of upfront TEVAR to treat uTBAD. A pilot
European trial (INSTEAD) compared the outcomes of upfront TEVAR to optimal medical therapy in 140
patients with uTBAD. Despite being significantly underpowered for all-cause mortality, the findings, along with
observational data suggest that medical therapy plus upfront TEVAR may be associated with decreased all-
cause and aortic-related mortality. We have also demonstrated from our completed surveys that there is
equipoise among practitioners with respect to the most appropriate treatment strategy in uTBAD. We propose
a pragmatic trial with centralized, telephone follow-up, remote blood pressure monitoring, a clinically relevant
hierarchical primary endpoint (mortality / aortic-related hospitalization), and multi-disciplinary teams of
investigators and patient advocates. The trial duration is 84 months with 5-month start-up. Average follow-up
is 4 year with a minimum of 2.5 years and maximum of 6 years for individuals enrolled early. IMPROVE-AD will
have 88% power to detect a 25% relative reduction in the incidence of the primary endpoint for patients
randomized to upfront MT plus TEVAR compared to MT plus surveillance for deterioration, assuming a 5 year
cumulative incidence of 20% death and 20% aortic-related hospitalization in the MT plus surveillance fo...

## Key facts

- **NIH application ID:** 10892225
- **Project number:** 5U24HL165029-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Sean M O'Brien
- **Activity code:** U24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $721,106
- **Award type:** 5
- **Project period:** 2023-07-21 → 2030-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892225

## Citation

> US National Institutes of Health, RePORTER application 10892225, 2/2 IMPRroving Outcomes in Vascular DisEase - Aortic Dissection (IMPROVE-AD) (5U24HL165029-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10892225. Licensed CC0.

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