New nasal spray form of bumetanide shows promise for heart failure treatment

American Heart AssociationNov 19 2024

A new nasal spray form of the medication bumetanide may reduce the tissue swelling caused by heart failure as effectively as the standard oral and intravenous formulations of the medication, according to late-breaking science presented today at the American Heart Association's Scientific Sessions 2024. The meeting, Nov. 16-18, in Chicago, is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science. This research is simultaneously published today in the American Heart Association journal Circulation.

Heart failure occurs when the heart does not pump blood as well as it should, resulting in decreased blood flow to organs and fluid buildup in the lungs and other tissues. Lifestyle changes, including controlling obesity, smoking cessation, being physically active, controlling high blood pressure and controlling blood glucose levels can help prevent the development of heart failure.

Medications used to treat heart failure include diuretics, which reduce tissue swelling and can be administered orally or intravenously. Bumetanide is one of the standard diuretics administered orally or intravenously to reduce tissue swelling from heart, kidney or liver disease by removing excess salt and water through the urine.

In this clinical trial called RSQ-777-02, researchers explored a new nasal spray form of bumetanide in healthy adults. They compared its absorption and ability to reduce swelling to those of oral and intravenous bumetanide among 68 adults who did not have heart failure or risk factors for heart failure at the time of enrollment.

In patients with heart failure, the body's ability to absorb oral medications in the stomach and gut often decreases as fluid overload builds up (this is called diuretic resistance) and, thus, oral medications are often least effective when the body needs them most. Having a diuretic that does not rely on gut absorption to be effective may be a very important tool to help patients with heart failure and other conditions without having to rely on intravenous administration of these medications, which can only be done at hospitals and in heart failure clinics."

Daniel Bensimhon, M.D., study presenting author, medical director of the Advanced Heart Failure/Mechanical Circulatory Support Program at Cone Health in Greensboro, North Carolina

The study found:

• The nasal spray was absorbed effectively and was safe, meaning that side effects were consistent with the other versions of administration and that it had fewer treatment-emergent adverse events compared to the oral version.
• Compared with the oral and IV versions of bumetanide, the nasal spray formulation led to a similar amount of urine output.
• Compared with the oral version, people treated with the nasal spray bumetanide reached a similar blood concentration, and the medication was absorbed 33% faster. The absorption rate of the IV form was faster than both the oral and nasal versions, however, the onset of sodium excretion through urine was faster with the nasal version, the authors noted. Previous research has suggested urinary sodium as a biomarker of diuretic response in heart failure.
• Study participants received all three forms of bumetanide in various order. The nasal and IV forms of bumetanide were absorbed at more reliable rates than the oral form for each study participant – a measure known as intrasubject variability. The nasal and IV forms had a variability in absorption of 27%, compared to >40% for the oral form, suggesting that the nasal and IV forms are more stable routes of dosing, the authors noted. This would be an advantage for the nasal spray over the oral form for self-administration of the medication at home, they added.

"We were surprised by how fast the nasal spray worked and by how variable the absorption of the oral drug was even in healthy subjects," Bensimhon said. "Patients who require diuretic treatment for swelling associated with chronic heart failure and liver disease may now have a new, self-administered option, particularly when they are unable to take their oral medication or it no longer works."

The study's primary limitation is that participants were healthy and did not have heart failure or risk factors for developing heart failure at the time of enrollment. Now that safety and tolerability have been established in healthy adults, the authors said they will be conducting future studies to evaluate the bioavailability and clinical effectiveness of intranasal bumetanide in patients with heart failure.

"We think this will be a valuable tool for treating heart failure by promoting care at home and potentially reducing the need for costly hospital admissions and readmissions," Bensimhon said. "Keeping patients at home is good for the patient and our health systems."

Study background and details:

• The RSQ-777-02 clinical trial was conducted at Orange County Research Center in Irvine, California, from December 2023 to April 2024.
• The study included 68 healthy adults, ages 18 to 55 years old, who did not have heart failure or risk factors for developing heart failure at the time of enrollment.
• 66.2% of participants identified as men; 33.8% as women. 60.3% of participants self-identified as white adults, 27.9% as Black adults, 10.3% as Asian adults and 1.5% self-identified as adults of "other" race. 32.4% identified as Hispanic or Latino ethnicity and 67.6% as not Hispanic or Latino ethnicity.
• The researchers administered nasal, oral and intravenous bumetanide. Each participant received all three forms of bumetanide in a varied order.
• Study participants were monitored on-site for 10 days.

Co-authors, disclosures and any additional funding sources are listed in the abstract. The study was funded and developed by Corstasis, the developer and manufacturer of the bumetanide nasal spray tested in the study. The study was conducted independently by the Orange County Research Center.