Loop Diuretics Administration and Acute Heart Failure | NCT01441245

Loop Diuretics Administration and Acute Heart Failure | NCT01441245 | Trialant

Description Module

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

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Continuous furosemide infusion	Experimental	The group that received the continuous infusion of furosemide (cIV), consisted of 30 patients;	Drug: furosemide infusion
Intermittent furosemide infusion	Experimental	The group that received the bolus infusion of furosemide (iIV), consisted of 27 patients	Drug: furosemide infusion

Interventions

Name	Type	Description	Arm Group Labels	Other Names
furosemide infusion	Drug	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

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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 period ranging from 72 h to 120 h.
Evaluation of Renal Function in Terms of Creatinine Levels at Discharge		from admission to discharge, an average of 12 days
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.	participants were followed for the duration of hospital stay, an average of 13 days
Evaluation of B-type Natriuretic Peptide (BNP) Levels From Admission to the End of Treatment		from admission to discharge, an average of 12 days
Change in Brain Natriuretic Peptide (BNP) Levels From Admission to the Discharge		participants were followed for the duration of hospital stay, an average of 13 days
Evaluation of Renal Function in Terms of Changes in GFR		from admission to discharge, an average of 12 days
Evaluation of Renal Function in Terms of GFR Values at Discharge		from admission to discharge, an average of 12 days

Secondary Outcomes

Measure	Description	Time Frame
Length of Hospitalization in the Two Groups	percentage of participants with hospital stay > 10 days	in-hospital
Dopamine Infusion During Hospitalization		in-hospital

Contacts/Locations Module

Name	Affiliation	Role
Alberto Palazzuoli, MD	Department of Internal Medicine, Cardiology Unit, Le Scotte Hospital, Siena	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Department of Internal Medicine, Cardiology Section Center		Siena		53100	Italy

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
25087085	Background	Palazzuoli A, Pellegrini M, Franci B, Beltrami M, Ruocco G, Gonnelli S, Angelini GD, Nuti R. Short and long-term effects of continuous versus intermittent loop diuretics treatment in acute heart failure with renal dysfunction. Intern Emerg Med. 2015 Feb;10(1):41-9. doi: 10.1007/s11739-014-1112-5. Epub 2014 Aug 3.
21366472	Result

Arm/Group Information

ID	Title	Description
FG000	cIV Group	The group that received the continuous infusion of furosemide (cIV), consisted of 30 patients.
FG001	iIV Group	The second group that received the same drug in bolus injections twice a day (iIV), consisted of 27 patients.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG00030 subjects FG00127 subjects
COMPLETED		FG00030 subjects FG00127 subjects
NOT COMPLETED		FG0000 subjects FG0010 subjects

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	cIV Group	The group that received the continuous infusion of furosemide (cIV), consisted of 30 patients.
BG001	iIV Group	The group that received the intermittent infusion of furosemide (iIV), consisted of 27 patients.

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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

Posted

Mean

Standard Deviation

time period ranging from 72 h to 120 h.

ID	Title	Description
OG000	Urine Output in cIV	Evaluation of urine output in Intermittent intravenous furosemide infusion group
OG001	Urine Output in iIV	Evaluation of urine output in Intermittent intravenous furosemide infusion group

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	cIV Group	The group that received the continuous infusion of furosemide (cIV), consisted of 30 patients.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
death	Cardiac disorders		Systematic Assessment	Cardiac death

More Info Module

Certain Agreements

Point of Contact

Title	Organization	Phone	Extension	Email
Alberto Palazzuoli MD, Cardiology Unit	Department of Internal Medicine, University of Siena, Le Scotte hospital, Siena, Italy	+39577585363		palazzuoli2@unisi.it

ID	Term
D004487	Edema

ID	Term
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Continuous variables are expressed as mean ± standard deviation (SD) and compared with t test for independent groups. p values <0.05 were considered significant.	t-test, 2 sided		0.04						2-Sided								Non-Inferiority or Equivalence	The sample size used was preliminarily calculated from each co-primary endpoint. We included the following assumptions: (1) a 30 % or more effect size in the difference between mean paired changes in continuous co-primary endpoints (eGFR, creatinine, BNP and diuresis); standard variation of each group data not exceeding 20 %; (2) alpha = 0.05 two-tailed and (3) power (1-beta) = 80 %.

Secondary

Length of Hospitalization in the Two Groups

percentage of participants with hospital stay > 10 days

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

Posted

Number

percentage of partecipants

in-hospital

ID	Title	Description
OG000	Lenght of Hospitalization in cIV	Prevalence of hospital stay > 10 days in continuous intravenous furosemide infusion.
OG001	Lenght of Hospitalization in iIV	Prevalence of hospital stay > 10 days in intermittent intravenous furosemide infusion.

Units	Counts
Participants	OG00030 OG00127

Title

Denominators

Categories

Title	Measurements
	OG00080 OG00144

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Qualitative variables are expressed as percentage and compared with chi-square test. p values <0.05 were considered significant.	Chi-squared		<0.01						2-Sided								Non-Inferiority or Equivalence	The sample size used was preliminarily calculated from each co-primary endpoint. We included the following assumptions: (1) a 30 % or more effect size in the difference between mean paired changes in continuous co-primary endpoints (eGFR, creatinine, BNP and diuresis); standard variation of each group data not exceeding 20 %; (2) alpha = 0.05 two-tailed and (3) power (1-beta) = 80 %.

Primary

Evaluation of Renal Function in Terms of Creatinine Levels at Discharge

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.

Posted

Mean

Standard Deviation

mg/dL

from admission to discharge, an average of 12 days

ID	Title	Description
OG000	Creatinine at Discharge in cIV	Mean creatinine at discharge in continuous intravenous fursoemide infusion.
OG001	Creatinine at Discharge in iIV	Mean creatinine at discharge in intermittent intravenous fursoemide infusion.

Units	Counts
Participants	OG00030 OG00127

Title

Denominators

Categories

Title	Measurements
	OG0001.78± 0.5 OG0011.51± 0.3

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		t-test, 2 sided		0.01						2-Sided								Non-Inferiority or Equivalence	The sample size used was preliminarily calculated from each co-primary endpoint. We included the following assumptions: (1) a 30 % or more effect size in the difference between mean paired changes in continuous co-primary endpoints (eGFR, creatinine, BNP and diuresis); standard variation of each group data not exceeding 20 %; (2) alpha = 0.05 two-tailed and (3) power (1-beta) = 80 %.

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.

Posted

Mean

Standard Deviation

mg/dL

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

ID	Title	Description
OG000	Changes in Creatinine in cIV Group	The group that received the continuous infusion of furosemide (cIV), consisted of 30 patients furosemide infusion: 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
OG001	Changes in Creatinine in iIV Group	The group that received the bolus infusion of furosemide (iIV), consisted of 27 patients furosemide infusion: 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

Units	Counts
Participants	OG00030 OG00127

Title

Denominators

Categories

Title	Measurements
	OG000-0.10± 0.30 OG001-0.50± 0.34

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		t-test, 2 sided		0.02						2-Sided								Non-Inferiority or Equivalence	The sample size used was preliminarily calculated from each co-primary endpoint. We included the following assumptions: (1) a 30 % or more effect size in the difference between mean paired changes in continuous co-primary endpoints (eGFR, creatinine, BNP and diuresis); standard variation of each group data not exceeding 20 %; (2) alpha = 0.05 two-tailed and (3) power (1-beta) = 80 %.

Primary

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

Posted

Mean

Standard Deviation

pg/ml

from admission to discharge, an average of 12 days

ID	Title	Description
OG000	BNP Levels at Discharge in cIV Group	The group that received the continuous infusion of furosemide (cIV), consisted of 30 patients furosemide infusion: 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
OG001	BNP Levels at Discharge in iIV Group	The group that received the bolus infusion of furosemide (iIV), consisted of 27 patients furosemide infusion: 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

Units	Counts
Participants	OG00030 OG00127

Title

Denominators

Categories

Title	Measurements
	OG000679± 397 OG001949± 548

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		t-test, 2 sided		0.04						2-Sided								Non-Inferiority or Equivalence	The sample size used was preliminarily calculated from each co-primary endpoint. We included the following assumptions: (1) a 30 % or more effect size in the difference between mean paired changes in continuous co-primary endpoints (eGFR, creatinine, BNP and diuresis); standard variation of each group data not exceeding 20 %; (2) alpha = 0.05 two-tailed and (3) power (1-beta) = 80 %.

Primary

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

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

Posted

Mean

Standard Deviation

pg/mL

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

ID	Title	Description
OG000	BNP Change in cIV	Evaluation of BNP change in Intermittent intravenous furosemide infusion group
OG001	BNP Change in iIV	Evaluation of BNP change in Intermittent intravenous furosemide infusion group

Units	Counts
Participants	OG00030 OG00127

Title

Denominators

Categories

Title	Measurements
	OG000-525± 615 OG001-148± 463

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Continuous variables are expressed as mean ± standard deviation (SD) and compared with t test for independent groups. p values <0.05 were considered significant.	t-test, 2 sided		0.03						2-Sided								Non-Inferiority or Equivalence	The sample size used was preliminarily calculated from each co-primary endpoint. We included the following assumptions: (1) a 30 % or more effect size in the difference between mean paired changes in continuous co-primary endpoints (eGFR, creatinine, BNP and diuresis); standard variation of each group data not exceeding 20 %; (2) alpha = 0.05 two-tailed and (3) power (1-beta) = 80 %.

Primary

Evaluation of Renal Function in Terms of Changes in GFR

Posted

Mean

Standard Deviation

(ml/min·1.73 m2)

from admission to discharge, an average of 12 days

ID	Title	Description
OG000	GFR Change in cIV	Mean GFR change in continuous intravenous fursoemide infusion.
OG001	GFR Change in iIV	Mean GFR change in intermittent intravenous fursoemide infusion.

Units	Counts
Participants	OG00030 OG00127

Title

Denominators

Categories

Title	Measurements
	OG000-3.18± 2.45 OG001-1.93± 2.90

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Continuous variables are expressed as mean ± standard deviation (SD) and compared with t test for independent groups. p values <0.05 were considered significant.	t-test, 2 sided		0.01						2-Sided								Non-Inferiority or Equivalence	The sample size used was preliminarily calculated from each co-primary endpoint. We included the following assumptions: (1) a 30 % or more effect size in the difference between mean paired changes in continuous co-primary endpoints (eGFR, creatinine, BNP and diuresis); standard variation of each group data not exceeding 20 %; (2) alpha = 0.05 two-tailed and (3) power (1-beta) = 80 %.

Primary

Evaluation of Renal Function in Terms of GFR Values at Discharge

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

Posted

Mean

Standard Deviation

(ml/min·1.73 m2)

from admission to discharge, an average of 12 days

ID	Title	Description
OG000	GFR at Discharge in cIV	Mean GFR at discharge in continuous intravenous fursoemide infusion.
OG001	GFR at Discharge in iIV	Mean GFR at discharge in intermittent intravenous fursoemide infusion.

Units	Counts
Participants	OG00030 OG00127

Title

Denominators

Categories

Title	Measurements
	OG00044.8± 6.1 OG00146.7± 6.1

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Continuous variables are expressed as mean ± standard deviation (SD) and compared with t test for independent groups. p values <0.05 were considered significant	t-test, 2 sided		0.05						2-Sided								Non-Inferiority or Equivalence	The sample size used was preliminarily calculated from each co-primary endpoint. We included the following assumptions: (1) a 30 % or more effect size in the difference between mean paired changes in continuous co-primary endpoints (eGFR, creatinine, BNP and diuresis); standard variation of each group data not exceeding 20 %; (2) alpha = 0.05 two-tailed and (3) power (1-beta) = 80 %.

Secondary

Dopamine Infusion During Hospitalization

Posted

Number

percentage of partecipants

in-hospital

ID	Title	Description
OG000	Dopamine Infusion in cIV	Prevalence of dopamine infusion in continuous intravenous furosemide infusion.
OG001	Dopamine Infusion in iIV	Prevalence of dopamine infusion in intermittent intravenous furosemide infusion.

Units	Counts
Participants	OG00030 OG00127

Title

Denominators

Categories

Title	Measurements
	OG00050 OG00126

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	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.	Chi-squared		<0.01						2-Sided								Non-Inferiority or Equivalence	The sample size used was preliminarily calculated from each co-primary endpoint. We included the following assumptions: (1) a 30 % or more effect size in the difference between mean paired changes in continuous co-primary endpoints (eGFR, creatinine, BNP and diuresis); standard variation of each group data not exceeding 20 %; (2) alpha = 0.05 two-tailed and (3) power (1-beta) = 80 %.