Bumetanide Nasal Spray Equivalent to Oral, IV Forms for Heart Failure

A nasal spray form of bumetanide achieved a comparable reduction in tissue swelling from heart failure as the standard oral and intravenous formulation of the medication, according to late-breaking science at the American Heart Association (AHA) Scientific Sessions 2024.¹

The RSQ-777-02 clinical trial evaluated the effect of the novel nasal spray form on healthy adults, including its absorption and ability to reduce tissue swelling, among a population of adults without 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 and, thus, oral medications are often least effective when the body needs them most,” said Daniel Bensimhon, MD, medical director of the Advanced Heart Failure/Mechanical Circulatory Support Program at Cone Health.² “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.”

Heart failure medications include oral or intravenous diuretics which can reduce heart-failure-related tissue swelling, including bumetanide, which removes excess salt and water through the urine. The RSQ-777-02 trial, conducted at the Orange County Research Center between December 2023 and April 2024, involved 68 adults aged 18 to 55 years.¹

Among the study population, 66.2% self-identified as men and 33.8% as women. Approximately 60.3% identified as White, 27.9% as Black, 10.3% as Asian, and 1.5% as “Other” race—32.4% identified as Hispanic or Latino, and 67.6% as not Hispanic or Latino ethnicity.

The study administered nasal, oral, and intravenous bumetanide to each participant in a varied order and monitored study participants on-site for 10 days. Overall, bumetanide nasal spray was absorbed effectively and remained tolerable, with consistent side effects with other forms of administration and fewer treatment-emergent adverse events (TEAEs) than the oral version.

Compared with oral and IV bumetanide, the nasal spray achieved a similar amount of urine output and reached a similar blood concentration, with a 33% faster absorption rate.² Although the absorption rate of IV bumetanide outpaced both other forms, the onset of sodium excretion in urine was faster with the nasal form.

As all participants received all 3 forms of bumetanide in various order, the nasal and IV forms were absorbed at “more reliable rates” than the oral form for each participant, according to Bensimhon and colleagues.

In particular, the nasal and IV bumetanide exhibited a variability of absorption of 27%, compared with >40% for the oral form, suggesting the nasal and IV forms are more stable and pointing to an advantage of the nasal spray over the oral form for at-home self-administration.

Overall, Bensimhon indicated the investigator’s surprise at the speed of the nasal spray, and the variability of the oral drug’s absorption, even in healthy individuals.² The team suggested the value of bumetanide nasal spray to promote care at home and potentially lower the need for hospital admission and re-admission could ease the burden on health systems.

“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,” Bensimhon added.²

References

1. _{Bonatto MG, Ferreira SA, Avila MS, et al. Effects of Sacubitril-Valsartan on Prevention of Cardiotoxicity in High-Risk Patients Undergoing Anthracycline Chemotherapy: A Double-Blind Randomized Placebo-Controlled Clinical Trial – The SARAH Trial. Presented at the American Heart Association (AHA) Scientific Sessions 2024. Chicago, Illinois. November 16-18, 2024.}
2. _{Nasal spray version of common diuretic has potential to help treat heart failure. American Heart Association. November 18, 2024. Accessed November 18, 2024. https://newsroom.heart.org/news/nasal-spray-version-of-common-diuretic-has-potential-to-help-treat-heart-failure.}