Findings from the RSQ-777-02 trial demonstrate the ability of a novel intranasal formulation of bumetanide, a standard loop diuretic, to reduce tissue swelling caused by heart failure (HF) as effectively as conventional oral and IV formulations.

Intrasubject variability in absorption was 27 percent for both bumetanide nasal spray (BNS) and the IV formulation; for the oral drug, the corresponding rate was >40 percent. These imply that the intranasal and IV routes were more stable dosing routes than oral administration even in healthy subjects, noted lead researcher Dr Daniel Bensimhon from the Advanced Heart Failure/Mechanical Circulatory Support Programme at Cone Health, Greensboro, North Carolina, US, at AHA 2024.

This, Bensimhon stressed, would be an edge for the nasal over the oral formulation for self-administration at home.

Moreover, maximum plasma concentration was achieved 33 percent faster with BNS compared with the oral formula, with a minimum time to maximum drug concentration of 14 vs 30 min for the oral drug. Urine output was similar at ~6 L across the three routes. [AHA 2024, abstract 4170722]

“We were surprised by how fast BNS worked and how variable the absorption of the oral drug was even in healthy subjects,” said Bensimhon.

BNS was well tolerated, with fewer treatment-emergent adverse events than oral bumetanide (16.2 percent vs 23.9 percent).

An effective parenteral alternative

In patients with volume overload, outpatient decongestion can be challenging due to the reduced bioavailability of oral diuretics. “In HF patients, the body’s ability to absorb oral medications in the stomach and gut often decreases as fluid overload builds up; thus, oral medications are often least effective when the body needs them most,” Bensimhon explained.

Thus, hospitalization for IV administration of diuretics may be required. However, persistent congestion at hospital discharge is common and is tied to high readmission rates and poor patient outcomes, pointed out Bensimhon and colleagues.

“Having a diuretic that does not rely on gut absorption to be effective may be a very important tool to help patients with HF and other conditions without having to rely on IV administration of these medications, which can only be done at hospitals and in HF clinics,” Bensimhon explained.

BNS offers an effective outpatient self-administered parenteral diuretic alternative for stable congested patients not responding to oral diuretics. It may also be useful in underserved populations and areas where access to acute care facilities and IV drugs is difficult or impossible.

A valuable homecare tool

“Patients who require diuretic treatment for swelling associated with chronic HF 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 said.

“[BNS could] be a valuable tool for treating HF by promoting care at home and potentially reducing the need for costly hospital admissions and readmissions. Keeping patients at home is good for the patient and our health systems,” Bensimhon said.

Sixty-eight adults (66.2 percent men, 10.3 percent Asian) who did not have HF or risk factors for developing HF prior to enrolment were included in the study. Participants received all three forms of bumetanide in a varied order and were monitored onsite for 10 days for each dosing strategy.

The findings support the potential of BNS in a healthy adult population. Future trials will explore the bioavailability and clinical efficacy of BNS in patients with HF.