A pH-neutral formulation of furosemide (Lasix) may be safe and effective for subcutaneous administration to patients with acute decompensated heart failure, according to the results of a phase II trial.
The single-center study had 41 patients randomized to a single dose of subcutaneous furosemide (at a fixed 80 mg over 5 hours) or IV furosemide (123 mg on average).
Nisha Gilotra, MD, of Johns Hopkins School of Medicine in Baltimore, and colleagues, in a study online in JACC: Heart Failure, found that 6-hour urine output was statistically no different between groups (median 1,425 mL for IV versus 1,350 mL for subcutaneous, P=0.84). Natriuresis, however, was higher in the subcutaneous furosemide group (32.8 mEq/l versus 7.3 mEq/l for the IV group, P=0.05).
Patients lost a similar amount of weight in 6 hours — an average of -1.5 kg for both groups (P=0.95).
As for safety, neither formulation was associated with worsening renal function, ototoxicity, or skin irritation. In addition, patients shared similar rates of 30-day hospitalization (52% for subcutaneous versus 42% for IV groups, P=0.55).
“There have been limited advancements in diuretic therapy in decompensated heart failure, despite diuretics serving as the mainstay for relief of congestion for several decades,” the team wrote. “This is the first study to examine the efficacy of a novel subcutaneous formulation of the loop diuretic furosemide administered by 5-hour fixed-dose infusion in patients presenting with worsening heart failure in the outpatient setting.”
“This method of decongestion may allow treatment at home and reduced heart failure resources and warrants further investigation.”
Prior formulations of subcutaneous furosemide were too alkaline, forcing it to be injected at low volumes at a time and causing frequent skin burns and stings, the authors noted. In addition, the attempted use of an elastomeric pump required catheter placement and continuous infusion, and was associated with complications such as abscess formation.
“In an attempt to address some of these hurdles to subcutaneous administration of furosemide, the scFurosemide used in this study was developed with a physiologic pH of 7.4 and the ability to administer it through an infusion pump,” the team said.
Based on the results, the 80 mg dose is “clearly an efficacious dose” for heart failure patients with acute volume overload, the researchers wrote.
In an accompanying editorial comment, Gary Francis, MD, and Tamas Alexy, MD, PhD, both of the University of Minnesota in Minneapolis, said: “If there were a simple pathway to manage the thousands of patients with acutely decompensated heart failure by using an effective and safe diuretic regimen, particularly if the treatment protocol reduced the need for prolonged, expensive hospitalizations and readmissions, it could be transformative in our current clinical practice.”
“It is conceivable that buffered subcutaneous furosemide formulation may eventually be self-administered by select patients at home, using a small patch pump. This strategy may reduce heart failure symptoms to the point that a trip to the emergency department or clinic would not be necessary. One may imagine that, in the future, the delivery system may even be made responsive to the individual’s volume status as measured by an internal pressure monitoring device.”
The study was conducted in subjects who were on average 57 years old. A total of 55% of the group were women, and there were no baseline differences between the groups.
Gilotra and colleagues acknowledged that the 5-hour administration required of the new formulation may be a barrier to wider use, although they reasoned that this length of time maximizes diuretic efficiency, allowing for a more steady-state concentration and prolonged diuresis.
Indeed, hourly urine output was greater in the IV group at hour 2 (425 mL versus 250 mL, P=0.02) and greater in the subcutaneous group at hour 6 (325 mL versus 125 mL, P=0.005), the investigators showed.
Francis and Alexy said that further studies will be required to evaluate how patients tolerate the repeated subcutaneous administration of furosemide and to better understand the optimal dose. In addition, “whether patients could readily self-administer the medication is open to question.”
The study was funded by scPharmaceuticals.
Gilotra and co-authors have no relationships listed and no conflicts of interest.
Francis disclosed financial relationships with Amgen, Cytokinetics, and Capricor Therapeutics.
Alexy reported having no relationships relevant to the paper.
Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner