Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2)

PROJECT SUMMARY
The Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2,
U01 NS080168) consists of two parallel randomized trials in patients with asymptomatic high- grade carotid
artery stenosis. One trial compares Intensive Medical Management (IMM) plus carotid endarterectomy to IMM
alone, and the other compares IMM plus carotid artery stenting to IMM alone. The trial is registered with
clinicaltrials.gov (NCT02089217).
Monitoring plays a crucial role in ensuring the protection of subjects and the validity of the science.
Additionally, monitoring is required for the CREST-2 trial by the FDA and NINDS. As of July 31, 2024, CREST-
2 has enrolled a total of 2,486 patients: 1,241 in the endarterectomy trial and 1,245 in the stenting trial.
Patients have been enrolled across 183 sites (171 US and 12 international). To be cost-effective in monitoring
these clinical sites, the CREST-2 Clinical Coordinating Center has taken on the responsibility of hiring and
managing the monitor rather than outsourcing the responsibility to a Clinical Research Organization.
During the course of the trial, monitoring has adapted for various reasons most notably the COVID-19
pandemic. Most monitoring visits were conducted on-site prior to the COVID-19 pandemic, remote monitoring
and quality control checks were implemented during the COVID-19 pandemic, and a combination of remote
and on-site monitoring have been used since March 2023. The approval of a previous administrative
supplement request provided funding to partially fund and support travel for our current Monitor. Through that
approval, we were able to resume site-level source document verification in the CREST-2 trial. From March
2023 to July 2024, a total of 41 monitoring visits have been conducted, including 25 onsite and 16 remote
visits. Furthermore, we have collaborated with our Statistical and Data Coordinating Center to develop forensic
and risk-based monitoring approaches, developed and deployed a survey on remote vs. in person monitoring
preferences to all CREST-2 sites, refined our site closeout monitoring process, developed a risk-based
monitoring prioritization system, built reports and dashboards in Smartsheet to track monitoring efforts, and
increased the frequency of data quality meetings to enhance data quality and completeness as we near the
end of the trial.
With approximately two years remaining of grant activities, we request additional funding through an
Administrative Supplement to continue monitoring efforts. The goals of this supplement are to continue onsite
and remote monitoring, close out CREST-2 sites once final follow-up visits occur, and help ensure a complete
and verifiable dataset.

Grant Number: 3U01NS080168-12S1
NIH Institute/Center: NIH
Principal Investigator: Thomas Brott