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Loop Diuretics Administration and Acute Heart Failure

Continuous Versus Intermittent Loop Diuretics Infusion Dosing in Acute Heart Failure: Effects on Renal Function, Outcome and BNP Levels

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01441245
Acronym
diurHF
Enrollment
57
Registered
2011-09-27
Start date
2010-04-30
Completion date
2017-12-28
Last updated
2018-01-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute Heart Failure

Keywords

acute heart failure, diuretics, BNP, Renal function, acute decompensated Heart Failure,, volume overload

Brief summary

Intravenous loop diuretics is the therapy most commonly used to treat pulmonary congestion and systemic fluid overload. In theory, continuous infusion should allow for a more consistent diuresis, avoiding the sodium reabsorption in the distal tubule as well as the neurohormonal activation. This should lead to renal function improvement and BNP decrease.

Detailed description

Patients were eligible if they were admitted with a primary diagnosis of ADHF, randomized within 12 h after hospital presentation, and with evidence of volume overload (pulmonary congestion) on a chest X-ray study and had BNP levels \>100 pg/ml. Patients also displayed mild to moderate renal dysfunction with creatinine values up to 1.4 mg/dl. Some patients were supported with non invasive ventilation before randomization. Once the initial 12 h dose was determined, patients were randomized using a 1:1 ratio using a computer-generated scheme to receive the furosemide dose either divided into a twice-daily bolus injection or in a continuous infusion (mixed as a 1:1 ratio in 5 % dextrose in water) for a time period ranging from 72 to 120 h. The randomization was casual, and the physicians did not previously know the assigned arm. The dose escalation and subsequent titration of furosemide was guided by clinical response in terms of urine output volume and body weight reduction .Before randomization, renal function parameters and BNP levels were measured in all patients. Subsequent titration of the furosemide dosage was at the discretion of the attending physician, but was guided by a dose-escalation algorithm based on the treatment response (weight loss and urine output volume), symptom improvement, changes in renal function, electrolyte balance, and chest radiography. The specific doses of furosemide and the use of additional agents to manage ADHF (dopamine, IV vasodilators, hypertonic saline infusion) were decided based upon blood pressure measurements, renal function evaluation and diuresis response. Supplementary treatment was left to the discretion of the treating physician. The duration of infusion was continued for up to 72 h, at 48 h the physicians had the possibility to adjust diuretic dose administration on the basis of the clinical response. After 72 h the treatment could be stopped or continued for an additional 36-48 h depending on the patient's condition and diuresis response. Acute kidney injury (AKI) was defined following the RIFLE criteria. Abbreviations: (AKI) Acute kidney injury (ADHF) Acute decompensated heart failure (BNP) B-type natriuretic peptide (CHD) Coronary heart disease (cIV) Continuous infusion (iIV) Intermittent infusione (eGFR)Estimated glomerular filtration rate (Hb) Hemoglobin (HF) Heart failure (Hct) Hematocrit (LVEF) Left ventricular ejection fraction (RBC) Red blood cells

Interventions

Patients were randomized in a 1:1 ratio to receive furosemide dose divided into twice-daily bolus injection (group 0) or continuous infusion (group 1)(mixed as a 1:1 ratio in 5% dextrose in water) for a time period ranging from 72 to 120 hours. The mean daily diuretic dosage was similar in the two groups. The median time from presentation to randomization was 16 hours, and the median duration of study-drug administration was 112± 24 hours

Sponsors

University of Siena
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No

Inclusion criteria

* Patients took part in the random sample selection if they met the diagnostic criteria for acute decompensated HF. * Patients with primary diagnosis of ADHF, volume overload with cardia dilation and LVEF \<50%, and had BNP levels \>100 pg/ml.

Exclusion criteria

* Patients were excluded if they had received more than 2 IV doses of furosemide or any continuous infusion of furosemide 1 month before randomization * If they had end-stage renal disease or the need for renal replacement therapy, isolated diastolic dysfunction. * Recent myocardial infarction

Design outcomes

Primary

MeasureTime frameDescription
Evaluation of Renal Function in Terms of GFR Values at Dischargefrom admission to discharge, an average of 12 days
Change in Brain Natriuretic Peptide (BNP) Levels From Admission to the Dischargeparticipants were followed for the duration of hospital stay, an average of 13 days
Evaluation of Renal Function in Terms of Changes in GFRfrom admission to discharge, an average of 12 days
Evaluation of Mean Urine Output Volume During the Infusion Periodtime period ranging from 72 h to 120 h.this study aimed to evaluate the effects of continuous infusion of furosemide in comparison to twice daily regimens at similar doses with respect to changes in renal function in terms of creatinine levels and GFR, urine output and BNP levels from admission to discharge
Evaluation of Renal Function in Terms of Creatinine Levels at Dischargefrom admission to discharge, an average of 12 days
Evaluation of Renal Function in Terms of Changes in Creatinine Levelsparticipants were followed for the duration of hospital stay, an average of 13 daysevaluation of renal function in terms of changes in creatinine levels during hospitalization in the two arms.
Evaluation of B-type Natriuretic Peptide (BNP) Levels From Admission to the End of Treatmentfrom admission to discharge, an average of 12 days

Secondary

MeasureTime frameDescription
Dopamine Infusion During Hospitalizationin-hospital
Length of Hospitalization in the Two Groupsin-hospitalpercentage of participants with hospital stay \> 10 days

Countries

Italy

Participant flow

Recruitment details

Department of Internal Medicine, Cardiology Section Centre into a Para-Intensive Unit (Siena, Italy) from April 2011 to December 2012.

Pre-assignment details

22 were excluded because of normal renal function at baseline, 11 for receiving different dosages of intravenous furosemide, 4 for isolated diastolic HF

Participants by arm

ArmCount
cIV Group
The group that received the continuous infusion of furosemide (cIV), consisted of 30 patients.
30
iIV Group
The group that received the intermittent infusion of furosemide (iIV), consisted of 27 patients.
27
Total57

Baseline characteristics

CharacteristiciIV GroupcIV GroupTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
21 Participants25 Participants46 Participants
Age, Categorical
Between 18 and 65 years
6 Participants5 Participants11 Participants
Age, Continuous73 years
STANDARD_DEVIATION 8
71 years
STANDARD_DEVIATION 7
72 years
STANDARD_DEVIATION 8
Region of Enrollment
Italy
27 participants30 participants57 participants
Sex: Female, Male
Female
13 Participants14 Participants27 Participants
Sex: Female, Male
Male
14 Participants16 Participants30 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
0 / 300 / 27
serious
Total, serious adverse events
14 / 309 / 27

Outcome results

Primary

Change in Brain Natriuretic Peptide (BNP) Levels From Admission to the Discharge

Time frame: participants were followed for the duration of hospital stay, an average of 13 days

Population: Continuous variables are expressed as mean ± standard deviation (SD) and compared with t test for independent groups. p values \<0.05 were considered significant.

ArmMeasureValue (MEAN)Dispersion
Urine Output in cIVChange in Brain Natriuretic Peptide (BNP) Levels From Admission to the Discharge-525 pg/mLStandard Deviation 615
Urine Output in iIVChange in Brain Natriuretic Peptide (BNP) Levels From Admission to the Discharge-148 pg/mLStandard Deviation 463
Comparison: Continuous variables are expressed as mean ± standard deviation (SD) and compared with t test for independent groups. p values \<0.05 were considered significant.p-value: 0.03t-test, 2 sided
Primary

Evaluation of B-type Natriuretic Peptide (BNP) Levels From Admission to the End of Treatment

Time frame: from admission to discharge, an average of 12 days

ArmMeasureValue (MEAN)Dispersion
Urine Output in cIVEvaluation of B-type Natriuretic Peptide (BNP) Levels From Admission to the End of Treatment679 pg/mlStandard Deviation 397
Urine Output in iIVEvaluation of B-type Natriuretic Peptide (BNP) Levels From Admission to the End of Treatment949 pg/mlStandard Deviation 548
p-value: 0.04t-test, 2 sided
p-value: 0.0195% CI: [1.65, 2.57]Regression, Linear
Primary

Evaluation of Mean Urine Output Volume During the Infusion Period

this study aimed to evaluate the effects of continuous infusion of furosemide in comparison to twice daily regimens at similar doses with respect to changes in renal function in terms of creatinine levels and GFR, urine output and BNP levels from admission to discharge

Time frame: time period ranging from 72 h to 120 h.

ArmMeasureValue (MEAN)Dispersion
Urine Output in cIVEvaluation of Mean Urine Output Volume During the Infusion Period2505 mLStandard Deviation 796
Urine Output in iIVEvaluation of Mean Urine Output Volume During the Infusion Period2140 mLStandard Deviation 468
Comparison: Continuous variables are expressed as mean ± standard deviation (SD) and compared with t test for independent groups. p values \<0.05 were considered significant.p-value: 0.04t-test, 2 sided
Primary

Evaluation of Renal Function in Terms of Changes in Creatinine Levels

evaluation of renal function in terms of changes in creatinine levels during hospitalization in the two arms.

Time frame: participants were followed for the duration of hospital stay, an average of 13 days

Population: All data were analyzed with intention-to-treat. Continuous variables are expressed as mean ± standard deviation (SD) and compared with t test for independent groups. p values \<0.05 were considered significant.

ArmMeasureValue (MEAN)Dispersion
Urine Output in cIVEvaluation of Renal Function in Terms of Changes in Creatinine Levels-0.10 mg/dLStandard Deviation 0.3
Urine Output in iIVEvaluation of Renal Function in Terms of Changes in Creatinine Levels-0.50 mg/dLStandard Deviation 0.34
p-value: 0.02t-test, 2 sided
Primary

Evaluation of Renal Function in Terms of Changes in GFR

Time frame: from admission to discharge, an average of 12 days

ArmMeasureValue (MEAN)Dispersion
Urine Output in cIVEvaluation of Renal Function in Terms of Changes in GFR-3.18 (ml/min·1.73 m2)Standard Deviation 2.45
Urine Output in iIVEvaluation of Renal Function in Terms of Changes in GFR-1.93 (ml/min·1.73 m2)Standard Deviation 2.9
Comparison: Continuous variables are expressed as mean ± standard deviation (SD) and compared with t test for independent groups. p values \<0.05 were considered significant.p-value: 0.01t-test, 2 sided
Primary

Evaluation of Renal Function in Terms of Creatinine Levels at Discharge

Time frame: from admission to discharge, an average of 12 days

Population: All data were analyzed with intention-to-treat. Continuous variables are expressed as mean ± standard deviation (SD) and compared with t test for independent groups. p values \<0.05 were considered significant.

ArmMeasureValue (MEAN)Dispersion
Urine Output in cIVEvaluation of Renal Function in Terms of Creatinine Levels at Discharge1.78 mg/dLStandard Deviation 0.5
Urine Output in iIVEvaluation of Renal Function in Terms of Creatinine Levels at Discharge1.51 mg/dLStandard Deviation 0.3
p-value: 0.01t-test, 2 sided
Primary

Evaluation of Renal Function in Terms of GFR Values at Discharge

Time frame: from admission to discharge, an average of 12 days

Population: Continuous variables are expressed as mean ± standard deviation (SD) and compared with t test for independent groups. p values \<0.05 were considered significant

ArmMeasureValue (MEAN)Dispersion
Urine Output in cIVEvaluation of Renal Function in Terms of GFR Values at Discharge44.8 (ml/min·1.73 m2)Standard Deviation 6.1
Urine Output in iIVEvaluation of Renal Function in Terms of GFR Values at Discharge46.7 (ml/min·1.73 m2)Standard Deviation 6.1
Comparison: Continuous variables are expressed as mean ± standard deviation (SD) and compared with t test for independent groups. p values \<0.05 were considered significantp-value: 0.05t-test, 2 sided
Secondary

Dopamine Infusion During Hospitalization

Time frame: in-hospital

ArmMeasureValue (NUMBER)
Urine Output in cIVDopamine Infusion During Hospitalization50 percentage of partecipants
Urine Output in iIVDopamine Infusion During Hospitalization26 percentage of partecipants
Comparison: Qualitative variables are expressed as percentage of partecipants and compared with chi-square test. p-value equal or lower than 0.05 are considered statistically significant.p-value: <0.01Chi-squared
Secondary

Length of Hospitalization in the Two Groups

percentage of participants with hospital stay \> 10 days

Time frame: in-hospital

Population: Qualitative variables are expressed as percentage and compared with chi-square test . p values \<0.05 were considered significant.

ArmMeasureValue (NUMBER)
Urine Output in cIVLength of Hospitalization in the Two Groups80 percentage of partecipants
Urine Output in iIVLength of Hospitalization in the Two Groups44 percentage of partecipants
Comparison: Qualitative variables are expressed as percentage and compared with chi-square test. p values \<0.05 were considered significant.p-value: <0.01Chi-squared

Source: ClinicalTrials.gov · Data processed: Mar 20, 2026