Nasal spray version of common diuretic has potential to help treat heart failure

American Heart Association Scientific Sessions 2024, Late Breaking Science Abstract 4170722

Research Highlights:

• A study testing a new nasal spray form of the medication bumetanide, a commonly prescribed diuretic, was found to be as safe and well-tolerated (meaning with no significant nasal irritation) in healthy adults in comparison to the oral and intravenous forms of the medication. The existing oral and intravenous forms of bumetanide are commonly prescribed for people with heart failure because they ease tissue swelling, a common cause of symptoms for people with heart failure.
• The nasal and IV forms of bumetanide had a variability in absorption of 27%, compared to >40% for the oral, pill form, suggesting that the nasal and IV forms are more stable routes of dosing, the authors noted.
• Compared with the oral and IV versions of bumetanide, the nasal spray form led to a similar amount of urine output.
• Use of the nasal spray form of bumetanide could make it easier for people with heart failure to treat themselves at home and reduce hospitalization, researchers noted.
• Note: The study featured in this news release is a research abstract. Abstracts presented at American Heart Association's scientific meetings are not peer-reviewed, and the findings are considered preliminary until published as full manuscripts in a peer-reviewed scientific journal.

Embargoed until 8:30 a.m. CT/9:30 a.m. ET, Monday, Nov. 18, 2024

This news release contains updated information from the researcher that was not in the abstract.

CHICAGO, Nov. 18, 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," said study presenting author Daniel Bensimhon, M.D., medical director of the Advanced Heart Failure/Mechanical Circulatory Support Program at Cone Health in Greensboro, North Carolina. "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."

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.

Statements and conclusions of studies that are presented at the American Heart Association's scientific meetings are solely those of the study authors and do not necessarily reflect the Association's policy or position. The Association makes no representation or guarantee as to their accuracy or reliability. Abstracts presented at the Association's scientific meetings are not peer-reviewed, rather, they are curated by independent review panels and are considered based on the potential to add to the diversity of scientific issues and views discussed at the meeting. The findings are considered preliminary until published as a full manuscript in a peer-reviewed scientific journal.

The Association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific Association programs and events. The Association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and biotech companies, device manufacturers and health insurance providers and the Association's overall financial information are available here.

Additional Resources:

• Multimedia is available on the right column of the release link.
• Link to abstract; and AHA Scientific Sessions 2024 Online Program Planner
• AHA health information: What is Heart Failure?
• AHA health information: Living with Heart Failure and Managing Advanced HF
• For more news at AHA Scientific Sessions 2024, follow us on X @HeartNews,#AHA24

###

About the American Heart Association

The American Heart Association is a relentless force for a world of longer, healthier lives. We are dedicated to ensuring equitable health in all communities. Through collaboration with numerous organizations, and powered by millions of volunteers, we fund innovative research, advocate for the public's health and share lifesaving resources. The Dallas-based organization has been a leading source of health information for a century. During 2024 - our Centennial year - we celebrate our rich 100-year history and accomplishments. As we forge ahead into our second century of bold discovery and impact, our vision is to advance health and hope for everyone, everywhere. Connect with us on heart.org, Facebook, X or by calling 1-800-AHA-USA1.

For Media Inquiries and AHA Expert Perspective:

AHA Communications & Media Relations in Dallas: 214-706-1173; [email protected]

John Arnst [email protected]

For Public Inquiries: 1-800-AHA-USA1 (242-8721)

heart.org and stroke.org