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

A new study has found that a nasal spray containing the drug bumetanide can reduce tissue swelling caused by heart failure as effectively as standard oral and intravenous forms of the drug. The findings were presented at the 2024 American Heart Association Scientific Sessions in Chicago, an important international forum for sharing the latest scientific advances and clinical practice updates in cardiovascular science. The study is also published in the American Heart Association journal Circulation.

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

Diuretics are used to treat heart failure, which reduce tissue swelling and can be given orally or intravenously. Bumetanide is one of the standard diuretics, given orally or intravenously to remove excess salt and water through urine and reduce swelling caused by heart, kidney, or liver disease.

In the RSQ-777-02 clinical trial, researchers studied a new nasal spray formulation of bumetanide in healthy people. They compared its absorption and ability to reduce swelling with oral and intravenous forms in 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 medications in the stomach and intestines often decreases as fluid accumulates (called diuretic resistance), and so oral medications are often least effective just when they are needed most,” said lead study author Dr. Daniel Bensimhon, 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 gastrointestinal absorption could be an important tool to help patients with heart failure and other conditions without requiring intravenous administration, which can only be done in hospitals and clinics," he added.

The study found:

• The nasal spray was well absorbed and safe, with side effects comparable to other forms of administration and fewer side effects than the oral version.
• Compared with oral and intravenous bumetanide, the nasal spray produced similar urine output.
• The nasal spray achieved similar blood concentrations as the oral version, but the drug was absorbed 33% faster. Although the intravenous form had the fastest absorption rate, urinary sodium excretion was faster with the nasal version. Previous studies have shown that urinary sodium levels may serve as a biomarker of diuretic response in heart failure.
• All study participants received the three forms of bumetanide in different orders. The nasal and intravenous forms were absorbed more consistently than the oral form, which is called within-subject variability. The nasal and intravenous forms had a 27% variability in absorption, compared with more than 40% for the oral form, indicating greater stability of the nasal and intravenous forms, the authors noted.

“We were surprised by how quickly the nasal spray worked and how variable the absorption of the oral drug was, even in healthy participants,” Bensimhon said. “Patients who require diuretic therapy to relieve swelling in chronic heart failure and liver disease may now have a new option for self-administration, especially when they cannot take their oral medication or it stops working.”

The main limitation of the study is that the participants were healthy and did not have heart failure or risk factors for heart failure at the time of participation. Now that safety and tolerability have been established in healthy adults, the authors plan to conduct further studies to evaluate the bioavailability and clinical efficacy of nasal bumetanide in patients with heart failure.

“We believe this will be a valuable tool for the treatment of heart failure, facilitating home care and potentially reducing the need for expensive hospitalizations and readmissions,” Bensimhon concluded. “Keeping patients at home is good for them and good for our health systems.”

Study details:

• The RSQ-777-02 clinical trial was conducted at the Orange County Research Center in Irvine, California, from December 2023 to April 2024.
• The study included 68 healthy adults aged 18 to 55 years who did not have heart failure or risk factors for its development at the time of participation.
• 66.2% of participants identified themselves as male, 33.8% as female. 60.3% of participants identified themselves as white, 27.9% as black, 10.3% as Asian, and 1.5% as "other." 32.4% of participants identified themselves as Hispanic, 67.6% did not.
• Participants received nasal, oral, and intravenous bumetanide in varying orders. Participants were followed on-site for 10 days.