Controlled decongestion by Reprieve therapy in acute heart failure: results of the TARGET‐1 and TARGET‐2 studies

Abstract

Aims Safe and effective decongestion is the main goal of therapy in acute heart failure (AHF). In the non‐randomized, prospective TARGET‐1 and TARGET‐2 studies (NCT03897842), we investigated whether adding the Reprieve System® (which continuously monitors urine output and delivers a matched volume of hydration fluid sufficient to maintain the set fluid balance rate) to standard diuretic‐based regimen improves decongestion in AHF. Methods and results The population consisted of 19 patients hospitalized with AHF (mean age 67 ± 10 years, 18 male, ejection fraction 34 ± 15%, median N‐terminal pro‐B‐type natriuretic peptide 4492 pg/mL). Patients served as their own controls: each patient underwent 24 h of standard diuretic therapy followed by 24 h of diuretics with Reprieve therapy (with normal saline used for matched volume replacement). The primary efficacy endpoint of actual fluid loss not exceeding the target fluid loss at the end of therapy was met in all 19 (100%) patients. The mean diuresis during Reprieve therapy was 6284 ± 2679 mL (vs. 1966 ± 1057 mL 24 h before therapy) and 2053 ± 888 mL (24 h after therapy) (both P < 0.0001). At the end of therapy, patient global assessment improved from 7.7 ± 1.1 to 3.0 ± 1.3 points (P < 0.001), central venous pressure decreased from 15.5 ± 5.3 mmHg to 12.8 ± 4.8 mmHg (P < 0.05) and the median urine sodium loss was 9.7 [3–13] mmol/h. The Reprieve therapy was safe, systolic blood pressure remained stable, mean creatinine dropped from 1.45 ± 0.4 mg/dL to 1.26 ± 0.4 mg/dL (P < 0.001) and biomarkers of renal injury did not change during treatment. Conclusions The Reprieve System in conjunction with diuretic therapy supports safe and controlled decongestion in AHF.

September 2019 at a glance: focus on devices

“…The primary efficacy endpoint of actual fluid loss not exceeding the target fluid loss at the end of therapy was met in all patients. Diuresis was larger, patients' symptoms improved, central venous pressure decreased, and serum creatinine dropped with the new device …”

“…Safe and effective treatment of congestion remains a major unmet need . Biegus et al . investigated the efficacy of adding to a standard diuretic‐based regimen a device which continuously monitors urine output and delivers a matched volume of hydration fluid sufficient to maintain the set fluid balance rate.…”

Technology‐assisted clinical care

“…In this issue of the Journal, there is a report of two early, simple, small non‐randomised trials of a deceptively simple but innovative piece of medical equipment, Reprieve Therapy™, a device that measures urine output and administers intravenous (IV) fluid at a rate that depends on the urine output . The idea is simple; the clinician wants to obtain fluid loss at a certain rate, but is uncertain how much urine flow the administered diuretics will achieve, so existing practice is to see how much is produced and then either adjust the subsequent dose or advise a change in fluid therapy to compensate for over‐diuresis.…”

Can saline repletion be the true TARGET for achieving fluid balance in acute heart failure?

“…In this issue of the Journal, Biegus and colleagues report their findings of two single‐arm, open‐label, single‐centre pilot studies that assessed the safety and tolerability of a proprietary platform that monitors urine output in real time (hourly) via a Foley catheter and delivers a matched volume of intravenous normal saline to maintain a pre‐set fluid balance in patients with ADHF receiving intravenous (IV) loop diuretic therapy . Of note, the study population included those who have already been admitted to the hospital with ADHF (with congestive signs and symptoms, elevated natriuretic peptide levels, and ∼8.6 kg self‐reported weight gain at admission) for ∼2 days.…”

“…Characterized as ‘controlled decongestion’ with the concept of maintaining plasma refill rate to avoid over‐diuresis, the investigators targeted a pre‐determined negative fluid balance (∼200 mL/h) to allow the clinician to reliably achieve their clinically‐determined ‘optimal’ negative fluid balance during treatment. The results were thought‐provoking – there was significantly increased diuresis/natriuresis and improvements in markers of decongestion compared with the preceding 24 h before the system was operational, even though patients were given much higher diuretic doses at the discretion of the treating physicians in an open‐label fashion without a parallel control group …”