FQHCs and similar healthcare systems often serve marginalized communities and populations that are underrepresented in healthcare research. Pragmatic trials conducted in these settings contribute to research findings that are applicable to more diverse populations.
The new Living Textbook section draws from the significant experiences of the NIH Collaboratory Trials to illustrate best practices and lessons learned. The new section covers:
Reducing burden for clinic staff in underresourced clinics
Reaching a diverse patient population
Engaging healthcare system partners early to accomplish practical goals
Building trust with key interest holders
Conducting effective pragmatic trials in underresourced clinics
Renato Lopes MD, PhD
Professor of Medicine, Division of Cardiology
Duke University Medical Center
Duke Clinical Research Institute
Keywords
Heart Failure; Chagas Disease; Underserved Population
Key Points
Chagas disease is a condition caused by the parasite Trypanosoma cruzi. One of the complications of Chagas is heart failure (HF). Though Latin America has historically borne the brunt of Chagas-related HF, incidence is increasing globally.
Chagas-related HF has unique characteristics, with lower prevalence of hypertension and diabetes, worse health-related quality of life, and higher hospitalization and mortality rates when compared to other types of HF. In short, though patients with Chagas-related HF are less likely to have classic HF risk factors, their event rates are higher. Furthermore, there’s a lack of clinical evidence to guide their treatment.
Prevention And Reduction of Adverse outcomes in Chagasic Heart failUre Trial Evaluation (PARACHUTE-HF) was a prospective randomized trial evaluating the effect of sacubitril/valsartan compared with enalapril in improving a hierarchical composite endpoint including cardiovascular (CV) death, HF hospitalization, and reduction in NT-proBNP levels – in that order, on the basis of clinical importance.
The study population consisted of 922 patients from 83 sites in 4 Latin American countries: Argentina, Brazil, Colombia, and Mexico. Participants had HF with reduced ejection fraction (HFrEF) and a confirmed diagnosis of Chagas disease.
After 12 weeks, the study team found that sacubitril/valsartan was superior to enalapril with respect to the hierarchical composite endpoint. These results were primarily driven by a 32% reduction in average NT-proBNP levels.
There were some limitations, including COVID-19-related changes in clinical practice that may have affected HF hospitalization rates and the observed treatment effect.
PARACHUTE-HF was the first major randomized trial studying HF treatment in HFrEF patients with Chagas disease. While sacubitril/valsartan has extensive clinical and real-world data supporting its effectiveness for HFrEF, this trial further supports its use in treating this specific population.
There is a need for rigorously conducted clinical trials in Chagas disease to better define the cardiovascular benefit/risk profile of new treatment options for this neglected and high-risk population. This trial provides a model for international collaboration among cardiologists and infectious disease physicians with a shared goal.
Discussion Themes
The pathophysiology of Chagas is complex. It includes chronic, low-intensity myocarditis, which can lead to changes in coagulation pathways and thrombotic events; a neurological tropism, which can cause sudden arrythmias; and an autoimmune component.
Dr. Lopes emphasized the impact that an intentional and informed coordinating center; carefully selected sites; deeply invested PIs; and a strong Data and Safety Monitoring Board (DSMB) had on the success of PARACHUTE-HF.
The NIH Pragmatic Trials Collaboratory has added a new section to the Living Textbook in the Building Partnerships and Teams to Ensure a Successful Trial chapter. The new section, Partnering With Underresourced Clinics to Conduct PCTs, focuses on partnering with federally qualified health centers (FQHCs) and other underresourced clinics to conduct pragmatic clinical trials.