Sequential Nephron Blockade in Acute Heart Failure
Status:
Unknown status
Trial end date:
2020-12-31
Target enrollment:
Participant gender:
Summary
Background - Volume overload is an important clinical target in acute heart failure
management (AHF), typically addressed using loop diuretics. An important and challenging
subset of heart failure patients exhibit fluid overload despite significant doses of loop
diuretics. One approach to overcome loop diuretic resistance is the addition of a
thiazide-type diuretic to produce diuretic synergy via "sequential nephron blockade".
Although potentially able to induce diuresis in patients otherwise resistant to high doses of
loop diuretics, this strategy has not been subjected to large-scale clinical trials to
establish safety and clinical efficacy.
Methods - Our trial is a multicentric, double blind, randomized clinical study, aiming to
recruit 310 patients with AHF and clinically evident volume overload. Study participants are
randomized to receive a standard diuretic therapy (intravenous loop diuretics as recommended
by current guidelines plus placebo) or SNB therapy (loop diuretics plus oral metolazone at
the dose of 5/10 mg once daily) on top of standard medical therapy. Mineralocorticoid
antagonists will be used in association with the two regimens according to blood potassium
level and kidney function at the discretion of the treating physician. The primary endpoint
is defined as the change in the serum creatinine level and the change in weight, considered
both as a bivariate response and with their single components, between the time of
randomization and 72 hours after randomization. Secondary endpoints include global well-being
and dyspnoea assessed by a visual-analogue scale, changes in body weight and net fluid loss,
proportion of patients free from congestion, treatment failure, changes in biomarker levels
and the composite of death, rehospitalization, or an emergency room visit within 60 days, as
well as the composite of total number of days hospitalized or death during the 60 days after
randomization.
Phase:
Phase 3
Details
Lead Sponsor:
Policlinico Casilino ASL RMB
Collaborators:
IRCCS San Raffaele Umberto I Hospital, Nocera Inferiore