ACTIV trials: cross-trial lessons learned for master protocol implementation.

The United States Government (USG) public-private partnership "Accelerating COVID-19 Treatment Interventions and Vaccines" (ACTIV) was launched to identify safe, effective therapeutics to treat patients with Coronavirus Disease 2019 (COVID-19) and prevent hospitalization, progression of disease, and death. Eleven original master protocols were developed by ACTIV, and thirty-seven therapeutic agents entered evaluation for treatment benefit. Challenges encountered during trial implementation led to innovations enabling initiation and enrollment of over 26,000 participants in the trials.

Lessons Learned from National Heart, Lung, and Blood Institute Covid-19 Clinical Trials.

AbstractIn response to the Covid-19 pandemic, the National Heart, Lung, and Blood Institute launched five multisite clinical trials testing candidate host tissue-directed medical interventions to hasten recovery, improve function, and reduce morbidity and mortality. Speed, flexibility, and collaboration were essential. This article from the Steering and Executive committees describes the Collaborating Network of Networks for Evaluating Covid-19 and Therapeutic Strategies (CONNECTS) research program that enrolled 6690 participants and evaluated 18 intervention strategies using 10 molecular agents across the care continuum (outpatient, inpatient, and post discharge), and reports lessons learned from this initiative.

American Heart Association Cardiogenic Shock Registry: Design and Implementation.

Background: Cardiogenic shock is a morbid complication of heart disease that claims the lives of more than 1 in 3 patients presenting with this syndrome. Supporting a unique collaboration across clinical specialties, federal regulators, payors, and industry, the American Heart Association volunteers and staff have launched a quality improvement registry to better understand the clinical manifestations of shock phenotypes, and to benchmark the management patterns, and outcomes of patients presenting with cardiogenic shock to hospitals across the United States.

Methods: Participating hospitals will enroll consecutive hospitalized patients with cardiogenic shock, regardless of etiology or severity.

Transcatheter or Surgical Replacement for Failed Bioprosthetic Aortic Valves.

Importance: The use of valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) has been rapidly expanding as an alternative treatment to redo surgical aortic valve replacement (SAVR) for failed bioprosthetic valves despite limited long-term data.

Objective: To assess mortality and morbidity in patients undergoing intervention for failed bioprosthetic SAVR.

Design, Setting, And Participants: This was a retrospective population-based cohort analysis conducted between January 1, 2015, and December 31, 2020, with a median (IQR) follow-up time of 2.

Surgery and transcatheter intervention for degenerative mitral regurgitation in the United States.

Objectives: We evaluated practice trends and 3-year outcomes of transcatheter edge-to-edge repair (TEER) and surgical repair for degenerative mitral regurgitation in the United States.

Methods: From the Centers for Medicare and Medicaid Services data (2012-2019), 53,117 mitral valve interventions (surgery or TEER) were performed for degenerative mitral regurgitation, identified by excluding rheumatic and congenital disease, endocarditis, myocardial infarction, cardiomyopathy, and concomitant or prior coronary revascularizations. Median follow-up was 2.

Infarct-related structural disconnection and delirium in surgical aortic valve replacement patients.

Objective: Although acute brain infarcts are common after surgical aortic valve replacement (SAVR), they are often unassociated with clinical stroke symptoms. The relationship between clinically "silent" infarcts and in-hospital delirium remains uncertain; obscured, in part, by how infarcts have been traditionally summarized as global metrics, independent of location or structural consequence. We sought to determine if infarct location and related structural connectivity changes were associated with postoperative delirium after SAVR.

Prospective Study of Risk Factors for Postoperative Atrial Fibrillation After Cardiac Surgery.

Introduction: To examine risk factors for new-onset postoperative atrial fibrillation (POAF) after cardiac surgery.

Methods: Patients enrolled in the Cardiothoracic Surgical Trials Network multicenter, randomized trial of rate control versus rhythm control for POAF were included. Predictors of POAF were determined using multivariable logistic regression.

Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.

Background: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure.

Methods: TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA.

Advances in Coronary Computed Tomographic Angiographic Imaging of Atherosclerosis for Risk Stratification and Preventive Care.

The diagnostic evaluation of coronary artery disease is undergoing a dramatic transformation with a new focus on atherosclerotic plaque. This review details the evidence needed for effective risk stratification and targeted preventive care based on recent advances in automated measurement of atherosclerosis from coronary computed tomography angiography (CTA). To date, research findings support that automated stenosis measurement is reasonably accurate, but evidence on variability by location, artery size, or image quality is unknown.

Gender Disparities in Cardiac Surgery Trials: Leadership, Authorship, and Patient Enrollment.

Background: Studies have highlighted the paucity of women-led randomized controlled trials (RCTs) in cardiovascular medicine. Whether this finding also applies to cardiac surgery has not been evaluated. In this study, we evaluate women authorship, leadership, and women enrollment in cardiac surgery RCTs.

Pacemaker implantation associated with tricuspid repair in the setting of mitral valve surgery: Insights from a Cardiothoracic Surgical Trials Network randomized trial.

Objectives: In a recent trial, tricuspid annuloplasty (TA) during mitral valve surgery (MVS) for degenerative mitral regurgitation and moderate or less tricuspid regurgitation (TR) reduced the composite rate of death, reoperation for TR, or TR progression at 2 years. However, this benefit was counterbalanced by an increase in implantation of permanent pacemakers (PPMs). In this study, we analyzed the timing, indications, and risk factors for these implantations.

Intimal hyperplasia, saphenous vein graft disease, and clinical outcomes: Insights from the CTSN VEST randomized trial.

Background: Diffuse intimal hyperplasia and graft irregularity adversely affect the long-term patency of saphenous vein grafts (SVGs) and clinical outcomes of patients undergoing coronary artery bypass grafting (CABG). The VEST trial evaluated the efficacy of external graft support in limiting the development of intimal hyperplasia (IH) at 1 year postsurgery. In the present secondary analysis, we explored the associations between graft disease and IH and clinical events.

Characteristics of Postoperative Atrial Fibrillation and the Effect of Posterior Pericardiotomy.

Background: Postoperative atrial fibrillation (POAF) is a frequent complication of cardiac surgery. However, only a few detailed descriptions of the arrhythmia have been reported. We aim to describe the characteristics, outcomes, and variables associated with POAF and to evaluate how posterior pericardiotomy (PP) affects POAF characteristics.

A Randomized Trial of Mesenchymal Stromal Cells for Moderate to Severe Acute Respiratory Distress Syndrome from COVID-19.

There are limited therapeutic options for patients with coronavirus disease (COVID-19)-related acute respiratory distress syndrome with inflammation-mediated lung injury. Mesenchymal stromal cells offer promise as immunomodulatory agents. Evaluation of efficacy and safety of allogeneic mesenchymal cells in mechanically-ventilated patients with moderate or severe COVID-19-induced respiratory failure.

Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial.

Background: Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection.

Objective: To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone.

Design: Double-blind, randomized, placebo-controlled, clinical trial.

External Support for Saphenous Vein Grafts in Coronary Artery Bypass Surgery: A Randomized Clinical Trial.

Importance: Intimal hyperplasia and subsequent saphenous vein graft failure may have significant adverse clinical effects in patients undergoing coronary artery bypass surgery. External support of saphenous vein grafts has the potential to prevent vein graft dilation and hence slow the rate of intimal hyperplasia and increase long-term vein patency.

Objective: To determine efficacy, as measured by intimal hyperplasia, and safety of an external saphenous vein graft support device in patients undergoing a coronary bypass graft procedure.

Evaluating Primary Endpoints for COVID-19 Therapeutic Trials to Assess Recovery.

Uncertainty regarding the natural history of coronavirus disease (COVID-19) led to difficulty in efficacy endpoint selection for therapeutic trials. Capturing outcomes that occur after hospital discharge may improve assessment of clinical recovery among hospitalized patients with COVID-19. Evaluate 90-day clinical course of patients hospitalized with COVID-19, comparing three distinct definitions of recovery.

The impact of perioperative stroke and delirium on outcomes after surgical aortic valve replacement.

Objective: The effects of stroke and delirium on postdischarge cognition and patient-centered health outcomes after surgical aortic valve replacement (SAVR) are not well characterized. Here, we assess the impact of postoperative stroke and delirium on these health outcomes in SAVR patients at 90 days.

Methods: Patients (N = 383) undergoing SAVR (41% received concomitant coronary artery bypass graft) enrolled in a randomized trial of embolic protection devices underwent serial neurologic and delirium evaluations at postoperative days 1, 3, and 7 and magnetic resonance imaging at day 7.

Rationale and design of a randomized trial evaluating an external support device for saphenous vein coronary grafts.

Background: Coronary artery bypass grafting (CABG) is the most common revascularization approach for the treatment of multi-vessel coronary artery disease. While the internal mammary artery is nearly universally used to bypass the left anterior descending coronary artery, autologous saphenous vein grafts (SVGs) are still the most frequently used conduits to grafts the remaining coronary artery targets. Long-term failure of these grafts, however, continues to limit the benefits of surgery.