The SPIRRIT-HFpEF trial, being led by Sweden’s Karolinska Institutet and the U.S.’s Duke Clinical Research Institute, is a randomized pragmatic clinical trial of spironolactone or eplerenone vs usual care focused on improving outcomes for the growing heart failure (HF) population.
The goal of the Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure with Preserved Ejection Fraction (SPIRRIT-HFpEF; NCT02901184) is to assess the potential efficacy of mineralocorticoid receptor antagonists in these patients, and to evaluate the feasibility of the pragmatic trial concept for a chronic HF intervention. This is the first registry-based randomized clinical trial (RRCT) in heart failure, and among the first to focus on a chronic health condition.
SPIRRIT-HFpEF is utilizing the Swedish Heart Failure Registry (SwedeHF, 2,550 patients) and the US Trial Innovation Network (TIN, 650 patients). This is a multicenter, prospective, parallel assignment, open-label treatment, blinded endpoint (PROBE) pragmatic phase 3 interventional trial. Patients are randomized 1:1 to open-label spironolactone (or eplerenone) in addition to usual care, vs. usual care alone.
“SPIRRIT-HFpEF is a highly productive collaboration between Sweden and the US, where we achieve two critical aims,” said Lars Lund, MD, PhD, professor of cardiology at the Karolinska Institutet, Karolinska University Hospital, Sweden. “The first is to determine whether generic and inexpensive drugs are effective in a common type of heart failure that has limited treatment options. The second is to build a unique, pragmatic trial infrastructure and collaboration that makes clinical trials much more efficient and inexpensive to conduct.”
The rationale for this innovative trial design was that conventional trials are complex, expensive and slow to enroll. SPIRRIT-HFpEF offers a pragmatic, efficient and inexpensive approach, using an existing registry to provide data for power and feasibility. This provides generalizable results on a potential use for inexpensive generic drugs.
“We hope to see results from SPIRRIT-HFpEF in 2024, as the enrollment delays seen during the COVID-19 pandemic are resolved,” said the DCRI’s Adam DeVore, MD, an associate professor of medicine at the Duke University Medical Center. “The study is investigating the important clinical question of how best to treat this common disorder and is likely to provide helpful input for future treatment guidelines. The infrastructure of SPIRRIT-HFpEF is also expected to be useful for future randomized pragmatic trials.”
HF is a severe and worsening public health issue, affecting approximately 6.2 million adults in the United States and 26 million worldwide, and accounting for more than 1 million hospitalizations per year in the U.S. Projected healthcare costs for HF are rising. The death rate from heart disease is decreasing while deaths from HF are increasing.
HF with preserved left ventricular ejection fraction (HFpEF) is a serious and rising public health concern with limited treatment options; HFpEF and HF with reduced ejection fraction (HFrEF) each account for around one-half of HF cases.
In HFrEF, treatment with the mineralocorticoid receptor antagonists (MRAs), spironolactone and eplerenone, reduces the risk of hospitalization for HF and death from progressive heart failure and sudden cardiac death. In the earlier randomized, double-blind Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study (NCT00094302), patients treated with spironolactone had a modest but not statistically significant improvement over placebo, but total hospitalizations were less. The potential benefits of these widely-available therapies in HFpEF and HF with mildly-reduced ejection fraction are not clearly established.
The trial – which was the subject of a National Institutes of Health Grand Rounds lecture on February 4, 2022 – is funded by the National Heart, Lung and Blood Institute; the Swedish Heart-Lung Foundation; the Swedish Research Council; and the Erling Persson Family Foundation.