STS News, Spring 2021 — Since its establishment approximately 15 years ago through government funding, the Cardiothoracic Surgical Trials Network (CTSN) has been involved in important research that addresses evidence gaps and answers meaningful questions in cardiothoracic surgery.
With the onset of the pandemic and the related public health emergency in early 2020, its scope of work dramatically changed after CTSN received two calls.
Instead of focusing on research topics such as mitral regurgitation, atrial fibrillation, and coronary artery disease, CTSN pivoted toward critically ill COVID-19 patients. This would be the first time that the Network would become involved in studying areas related to infectious disease.
The first request was from an industry partner that was exploring the possibility of using stem cells for patients with acute respiratory distress syndrome (ARDS) as a result of COVID-19. At the time, the pandemic left large numbers of people suffering with ARDS and requiring ventilation in intensive care units, with dismal outcomes.
The company invited CTSN researchers to help evaluate its allogeneic mesenchymal stem cell product via a randomized, controlled trial. It was thought that this therapy could have immunomodulatory properties capable of counteracting the cytokine storm associated with the inflammatory conditions related to COVID-19.
While there was some initial resistance from CTSN leadership about becoming involved in this trial, Peter K. Smith, MD, from Duke University in Durham, North Carolina, and Michael J. Mack, MD, an STS Past President from Baylor Scott & White Health in Plano, Texas, decided that the trial was in line with CTSN’s mandate to rigorously evaluate novel therapies for public health imperatives; thus, they led the charge. Both Drs. Smith and Mack are principal investigators for their respective institutions, which are Core Clinical Centers in CTSN.
“The two of us said, ‘we’ll do this.’ So we designed and executed a trial for stem cell infusion in COVID-19 patients who were on ventilators,” explained Dr. Smith. “We created teams that were headed by surgeons but also included pulmonologists, critical care experts, hospitalists, and infectious disease specialists.”
“We've shown that we can make a major contribution to a national effort that's much larger than just cardiothoracic surgery.”
Origin of CTSN
The idea to form CTSN originally was conceived in 2004 after NHLBI challenged a working group of cardiac surgeons to assess the state of cardiac surgery research, identify critical gaps in current knowledge, and determine areas of opportunity.
Based on the group’s primary recommendation to form a cardiovascular surgery clinical network, NHLBI, in collaboration with the National Institute of Neurologic Disorders and Stroke and the Canadian Institutes for Health Research, created CTSN in 2007, with the mission to design, conduct, and analyze multiple, collaborative clinical trials that evaluate surgical interventions and related management approaches for the treatment of cardiovascular disease in adult patients.
During that time, Timothy J. Gardner, MD, from ChristianaCare Center for Heart & Vascular Health in Philadelphia, Pennsylvania, was a medical officer in the NHLBI Division of Cardiovascular Diseases and helped drive the program through NIH. Dr. Gardner was the first surgical chair of the CTSN steering committee, which is now led by A. Marc Gillinov, MD, from the Cleveland Clinic in Ohio.
Importantly, CTSN trials reflect the multidisciplinary partnership of many leading cardiothoracic surgeons, cardiologists, and neurologists; the infrastructure increases the efficiency of clinical research by providing a “clinical laboratory” in which multiple clinical questions can be asked without having to create a new infrastructure for each one.
“The most exciting part of the growth of the Cardiothoracic Surgical Trials Network and the ensuing work was helping a disparate group of investigators and site teams come together as a cohesive whole and answer the most important questions in cardiac surgical practice,” said Miller. “In this process, which was slow and challenging, the Network became a powerful clinical trial platform.”
Since its inception, CTSN has grown to 95 sites (60 in the US and 35 in Europe and South America) and been involved in approximately 20 trials—which is significant, considering the length of each trial from start to finish averages 3 to 7 years. With the enrollment of more than 2,000 patients in randomized trials and more than 14,000 patients in observational studies, CTSN is among the top performers of NHLBI- and NIH-sponsored networks.
“We want to be bigger, better, faster, stronger.”
While COVID-19 has consumed much of CTSN’s time this past year, the group also has been working on other impactful research.
Some of the more prominent topics in the CTSN portfolio include rate control versus rhythm control for postoperative atrial fibrillation, surgical treatment of ischemic mitral regurgitation, surgical ablation of atrial fibrillation during mitral valve surgery, the management of postoperative atrial fibrillation after coronary artery bypass grafting, and neuroprotection in patients undergoing aortic valve replacement. Many of these trials have resulted not only in peer-reviewed articles in high-profile publications, but also in changes to clinical practice recommendations.
For example, trial results focusing on surgical treatment of ischemic mitral regurgitation altered clinical guidelines in the US, Canada, and Europe and, as a result, transformed clinical practice, explained Dr. Gelijns.
Future Plans for CTSN
Described by Dr. Mack as an “inclusive, not exclusive” network, CTSN always is looking to expand and welcome additional sites (US and international) that serve underrepresented patient populations and young investigators who have special interests in diversity, inclusion, and health care disparities. It’s important to note that a major secondary purpose of CTSN is to develop qualified clinical investigators from the specialty who are able to design, develop, and execute clinical trials.
“In the early years, there were only a handful of investigators who were cardiothoracic surgeons and able to design and conduct clinical trials,” said Dr. Smith. “This was a major deficit and was specifically addressed with CTSN funding. The Network since has served as a training ground for principal investigators, so now there is an abundance of seasoned senior investigators and a large pipeline of formally trained young surgeon scientists.”
In addition to expanding the network, Dr. Mack would like to see CTSN enroll more patients, more quickly, in larger trials with longer-term follow up, which ultimately will bode well for cardiothoracic surgery.
“We want to be bigger, better, faster, stronger,” he said.
For more information about CTSN or to learn how to become involved, visit ctsurgerynet.org.
Read the STS press release.