Clinical trial NCT02638142: Loop Diuretic Therapy in Acutely Decompensated Heart Failure
Official title: Continuous Versus Bolus Intermittent Loop Diuretic Infusion in Acutely Decompensated Heart Failure: Evaluation of Renal Function, Congestion Signs, BNP and Outcome
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acute Heart Failure
Keywords: loop diuretic
heart failure
renal dysfunction
congestion signs
BNP
Lead sponsor: University of Siena
Sponsor class: OTHER
Collaborators: name: Azienda Ospedaliera di Padova
name: Ospedale Madonna della Navicella
name: University of Roma La Sapienza
First posted: 2015-12-22
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: patients who met diagnostic criteria for ADHF, independently from systolic function by exhibiting: at least one symptom at rest between dyspnea, orthopnea, peripheral edema and major fatigue; and at least two clinical signs including rales, pulmonary congestion on chest radiography, jugular vein dilatation and a third heart sound. An elevation in blood BNP \>100 pg/ml was considered supportive for a diagnosis of ADHF

Brief summary: DiurHF is a prospective, multicenter, observational, study that compares continuous with intermittent infusion of furosemide in patients admitted with a diagnosis of ADHF. Previous pilot study design was planned to anticipate a larger multicenter trial able to definitively evaluate the optimal loop diuretic use strategy in patients with ADHF.

Detailed description: The use of intravenous loop diuretics is a cornerstone of therapy for acutely decompensated heart failure (ADHF); significant concerns have been raised regarding risks and benefits of loop diuretics, particularly about dosage and administration regimen.

Recent guidelines recommend the use of these drugs to reduce left ventricular filling pressure, avoid pulmonary edema, and alleviate peripheral fluid retention.

Some studies have provided guidelines for the administration of these drugs in clinical practice, but data interpretation remains challenging due to the frequent exclusion of patients with kidney disease from major ADHF clinical trials. Therefore, it is not clear if continuous infusion is better than intermittent boluses in terms of decongestion, maintenance of renal filtration function and prognosis.

On the other hand, continuous administration should provide a more constant delivery of the drug into the tubule, potentially reducing these phenomena.

The aim of the study is to evaluate the better loop diuretic intravenous administration in terms of renal function, congestion signs, BNP and outcome.

Eligibility criteria: Inclusion Criteria:

* Patients over 18 years;
* Patients with diagnosis of ADHF(dyspnea, orthopnea, peripheral edema or major fatigue and at least two clinical signs including rales, hepatomegaly, pulmonary congestion on chest radiography, jugular vein dilatation, or a third heart sound);
* Blood BNP \> 100 pg/mL;

ADHF: Acute Decompensated Heart Failure; BNP: B-type Natriuretic Peptide; IV: IntraVenous; LVEF: Left Ventricular Ejection Fraction.

Exclusion Criteria:

* Patients who receive more than 40 mg of IV furosemide;
* End-Stage renal disease or renal replacement therapy;
* Recent myocardial infarction (within thirty days of screening);
* Systolic blood pressure \< 80 mmHg;
* Creatinine levels \> 4 mg/dL;
* Patients affected by sepsis, liver diseases, inflammatory diseases or neoplastic diseases.

Primary outcomes:
measure: Cardiac death and rehospitalization for HF
timeFrame: 180 days
Secondary outcomes:
measure: length of hospital stay (days)
timeFrame: From date of randomization until the discharge (7-12 days)
measure: Inotropes agents
timeFrame: From date of randomization until the discharge (7-12 days)
measure: hypertonic saline solution
timeFrame: From date of randomization until the discharge (7-12 days)
measure: Acute kidney injury
timeFrame: From date of randomization until the discharge (7-12 days)
measure: Body weight changes
timeFrame: from admission to discharge (7-12 days)
measure: Diuresis
timeFrame: from admission to discharge (7-12 days)
measure: BNP changes
timeFrame: From date of randomization until the discharge (7-12 days)
measure: BUN changes
timeFrame: From date of randomization until the discharge (7-12 days)
measure: Reduction of edema
timeFrame: From date of randomization until the discharge (7-12 days)
measure: Reduction of dyspnea
timeFrame: From date of randomization until the discharge (7-12 days)
measure: Regression of pulmonary congestion
timeFrame: From date of randomization
measure: Diuretic efficiency: (Weight loss/days of infusion)/ (Mean daily furosemide dosage/40 mg of furosemide)
timeFrame: From hospital admission until the discharge (7-12 days)
measure: High (> 125 mg/die) versus low (<125 mg/die) intravenous diuretic dosage
timeFrame: 180 days
measure: Diuretic efficiency: (Weight loss/days of infusion)/ (Mean daily furosemide dosage/40 mg of furosemide)
timeFrame: 180 days
Other outcomes:
Locations:
city: Chioggia
country: Italy
facility: Ospedale Madonna della Navicella
state: Venezia
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Roma
country: Italy
facility: University of Rome La Sapienza
city: Siena,
country: Italy
facility: Department of Internal Medicine, Cardiovascular Diseases Unit
Study officials:
affiliation: University of Siena
name: Alberto Palazzuoli, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Palazzuoli A, Pellegrini M, Ruocco G, Martini G, Franci B, Campagna MS, Gilleman M, Nuti R, McCullough PA, Ronco C. Continuous versus bolus intermittent loop diuretic infusion in acutely decompensated heart failure: a prospective randomized trial. Crit Care. 2014 Jun 28;18(3):R134. doi: 10.1186/cc13952.
citation: Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, LeWinter MM, Deswal A, Rouleau JL, Ofili EO, Anstrom KJ, Hernandez AF, McNulty SE, Velazquez EJ, Kfoury AG, Chen HH, Givertz MM, Semigran MJ, Bart BA, Mascette AM, Braunwald E, O'Connor CM; NHLBI Heart Failure Clinical Research Network. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011 Mar 3;364(9):797-805. doi: 10.1056/NEJMoa1005419.
citation: Lala A, McNulty SE, Mentz RJ, Dunlay SM, Vader JM, AbouEzzeddine OF, DeVore AD, Khazanie P, Redfield MM, Goldsmith SR, Bart BA, Anstrom KJ, Felker GM, Hernandez AF, Stevenson LW. Relief and Recurrence of Congestion During and After Hospitalization for Acute Heart Failure: Insights From Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure (DOSE-AHF) and Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARESS-HF). Circ Heart Fail. 2015 Jul;8(4):741-8. doi: 10.1161/CIRCHEARTFAILURE.114.001957. Epub 2015 Jun 3.
citation: ter Maaten JM, Dunning AM, Valente MA, Damman K, Ezekowitz JA, Califf RM, Starling RC, van der Meer P, O'Connor CM, Schulte PJ, Testani JM, Hernandez AF, Tang WH, Voors AA. Diuretic response in acute heart failure-an analysis from ASCEND-HF. Am Heart J. 2015 Aug;170(2):313-21. doi: 10.1016/j.ahj.2015.05.003. Epub 2015 May 9.
citation: Voors AA, Davison BA, Teerlink JR, Felker GM, Cotter G, Filippatos G, Greenberg BH, Pang PS, Levin B, Hua TA, Severin T, Ponikowski P, Metra M; RELAX-AHF Investigators. Diuretic response in patients with acute decompensated heart failure: characteristics and clinical outcome--an analysis from RELAX-AHF. Eur J Heart Fail. 2014 Nov;16(11):1230-40. doi: 10.1002/ejhf.170. Epub 2014 Oct 7.
citation: Palazzuoli A, Ruocco G, Vescovo G, Valle R, Di Somma S, Nuti R. Rationale and study design of intravenous loop diuretic administration in acute heart failure: DIUR-AHF. ESC Heart Fail. 2017 Nov;4(4):479-486. doi: 10.1002/ehf2.12226. Epub 2017 Oct 4.