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Trial record 1 of 4 for:    21366472 [PUBMED-IDS]
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Loop Diuretics Administration and Acute Heart Failure (diurHF)

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ClinicalTrials.gov Identifier: NCT01441245
Recruitment Status : Completed
First Posted : September 27, 2011
Results First Posted : February 2, 2016
Last Update Posted : January 23, 2018
Sponsor:
Information provided by (Responsible Party):
Alberto Palazzuoli MD PhD, University of Siena

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Acute Heart Failure
Intervention Drug: furosemide infusion
Enrollment 57
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
Arm/Group Title cIV Group iIV Group
Hide Arm/Group Description The group that received the continuous infusion of furosemide (cIV), consisted of 30 patients. The second group that received the same drug in bolus injections twice a day (iIV), consisted of 27 patients.
Period Title: Overall Study
Started 30 27
Completed 30 27
Not Completed 0 0
Arm/Group Title cIV Group iIV Group Total
Hide Arm/Group Description The group that received the continuous infusion of furosemide (cIV), consisted of 30 patients. The group that received the intermittent infusion of furosemide (iIV), consisted of 27 patients. Total of all reporting groups
Overall Number of Baseline Participants 30 27 57
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 27 participants 57 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
5
  16.7%
6
  22.2%
11
  19.3%
>=65 years
25
  83.3%
21
  77.8%
46
  80.7%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 30 participants 27 participants 57 participants
71  (7) 73  (8) 72  (8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 27 participants 57 participants
Female
14
  46.7%
13
  48.1%
27
  47.4%
Male
16
  53.3%
14
  51.9%
30
  52.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Italy Number Analyzed 30 participants 27 participants 57 participants
30 27 57
1.Primary Outcome
Title Evaluation of Mean Urine Output Volume During the Infusion Period
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Urine Output in cIV Urine Output in iIV
Hide Arm/Group Description:
Evaluation of urine output in Intermittent intravenous furosemide infusion group
Evaluation of urine output in Intermittent intravenous furosemide infusion group
Overall Number of Participants Analyzed 30 27
Mean (Standard Deviation)
Unit of Measure: mL
2505  (796) 2140  (468)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Urine Output in cIV, Urine Output in iIV
Comments Continuous variables are expressed as mean ± standard deviation (SD) and compared with t test for independent groups. p values <0.05 were considered significant.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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 %.
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
2.Primary Outcome
Title Evaluation of Renal Function in Terms of Creatinine Levels at Discharge
Hide Description [Not Specified]
Time Frame from admission to discharge, an average of 12 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Creatinine at Discharge in cIV Creatinine at Discharge in iIV
Hide Arm/Group Description:
Mean creatinine at discharge in continuous intravenous fursoemide infusion.
Mean creatinine at discharge in intermittent intravenous fursoemide infusion.
Overall Number of Participants Analyzed 30 27
Mean (Standard Deviation)
Unit of Measure: mg/dL
1.78  (0.5) 1.51  (0.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Creatinine at Discharge in cIV, Creatinine at Discharge in iIV
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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 %.
Statistical Test of Hypothesis P-Value 0.01
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
3.Primary Outcome
Title Evaluation of Renal Function in Terms of Changes in Creatinine Levels
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Changes in Creatinine in cIV Group Changes in Creatinine in iIV Group
Hide Arm/Group Description:

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

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

Overall Number of Participants Analyzed 30 27
Mean (Standard Deviation)
Unit of Measure: mg/dL
-0.10  (0.30) -0.50  (0.34)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Changes in Creatinine in cIV Group, Changes in Creatinine in iIV Group
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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 %.
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
4.Primary Outcome
Title Evaluation of B-type Natriuretic Peptide (BNP) Levels From Admission to the End of Treatment
Hide Description [Not Specified]
Time Frame from admission to discharge, an average of 12 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title BNP Levels at Discharge in cIV Group BNP Levels at Discharge in iIV Group
Hide Arm/Group Description:

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

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

Overall Number of Participants Analyzed 30 27
Mean (Standard Deviation)
Unit of Measure: pg/ml
679  (397) 949  (548)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BNP Levels at Discharge in cIV Group, BNP Levels at Discharge in iIV Group
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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 %.
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection BNP Levels at Discharge in cIV Group, BNP Levels at Discharge in iIV Group
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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 %.
Statistical Test of Hypothesis P-Value 0.01
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 2.06
Confidence Interval (2-Sided) 95%
1.65 to 2.57
Estimation Comments BNP levels at discharge >500 pg/ml (RR: 2.06 [1.65–2.57];).
5.Primary Outcome
Title Change in Brain Natriuretic Peptide (BNP) Levels From Admission to the Discharge
Hide Description [Not Specified]
Time Frame participants were followed for the duration of hospital stay, an average of 13 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Continuous variables are expressed as mean ± standard deviation (SD) and compared with t test for independent groups. p values <0.05 were considered significant.
Arm/Group Title BNP Change in cIV BNP Change in iIV
Hide Arm/Group Description:
Evaluation of BNP change in Intermittent intravenous furosemide infusion group
Evaluation of BNP change in Intermittent intravenous furosemide infusion group
Overall Number of Participants Analyzed 30 27
Mean (Standard Deviation)
Unit of Measure: pg/mL
-525  (615) -148  (463)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection BNP Change in cIV, BNP Change in iIV
Comments Continuous variables are expressed as mean ± standard deviation (SD) and compared with t test for independent groups. p values <0.05 were considered significant.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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 %.
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
6.Primary Outcome
Title Evaluation of Renal Function in Terms of Changes in GFR
Hide Description [Not Specified]
Time Frame from admission to discharge, an average of 12 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title GFR Change in cIV GFR Change in iIV
Hide Arm/Group Description:
Mean GFR change in continuous intravenous fursoemide infusion.
Mean GFR change in intermittent intravenous fursoemide infusion.
Overall Number of Participants Analyzed 30 27
Mean (Standard Deviation)
Unit of Measure: (ml/min·1.73 m2)
-3.18  (2.45) -1.93  (2.90)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection GFR Change in cIV, GFR Change in iIV
Comments Continuous variables are expressed as mean ± standard deviation (SD) and compared with t test for independent groups. p values <0.05 were considered significant.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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 %.
Statistical Test of Hypothesis P-Value 0.01
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
7.Primary Outcome
Title Evaluation of Renal Function in Terms of GFR Values at Discharge
Hide Description [Not Specified]
Time Frame from admission to discharge, an average of 12 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Continuous variables are expressed as mean ± standard deviation (SD) and compared with t test for independent groups. p values <0.05 were considered significant
Arm/Group Title GFR at Discharge in cIV GFR at Discharge in iIV
Hide Arm/Group Description:
Mean GFR at discharge in continuous intravenous fursoemide infusion.
Mean GFR at discharge in intermittent intravenous fursoemide infusion.
Overall Number of Participants Analyzed 30 27
Mean (Standard Deviation)
Unit of Measure: (ml/min·1.73 m2)
44.8  (6.1) 46.7  (6.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection GFR at Discharge in cIV, GFR at Discharge in iIV
Comments Continuous variables are expressed as mean ± standard deviation (SD) and compared with t test for independent groups. p values <0.05 were considered significant
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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 %.
Statistical Test of Hypothesis P-Value 0.05
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
8.Secondary Outcome
Title Length of Hospitalization in the Two Groups
Hide Description percentage of participants with hospital stay > 10 days
Time Frame in-hospital
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Qualitative variables are expressed as percentage and compared with chi-square test . p values <0.05 were considered significant.
Arm/Group Title Lenght of Hospitalization in cIV Lenght of Hospitalization in iIV
Hide Arm/Group Description:
Prevalence of hospital stay > 10 days in continuous intravenous furosemide infusion.
Prevalence of hospital stay > 10 days in intermittent intravenous furosemide infusion.
Overall Number of Participants Analyzed 30 27
Measure Type: Number
Unit of Measure: percentage of partecipants
80 44
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Lenght of Hospitalization in cIV, Lenght of Hospitalization in iIV
Comments Qualitative variables are expressed as percentage and compared with chi-square test. p values <0.05 were considered significant.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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 %.
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
9.Secondary Outcome
Title Dopamine Infusion During Hospitalization
Hide Description [Not Specified]
Time Frame in-hospital
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dopamine Infusion in cIV Dopamine Infusion in iIV
Hide Arm/Group Description:
Prevalence of dopamine infusion in continuous intravenous furosemide infusion.
Prevalence of dopamine infusion in intermittent intravenous furosemide infusion.
Overall Number of Participants Analyzed 30 27
Measure Type: Number
Unit of Measure: percentage of partecipants
50 26
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dopamine Infusion in cIV, Dopamine Infusion in iIV
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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 %.
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Time Frame The 6-months follow-up events encompassed: cardiac death, rehospitalization for all cardiovascular causes, and severe renal insufficiency needing hemodialysis.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title cIV Group iIV Group
Hide Arm/Group Description The group that received the continuous infusion of furosemide (cIV), consisted of 30 patients. The second group that received the same drug in bolus injections twice a day (iIV), consisted of 27 patients.
All-Cause Mortality
cIV Group iIV Group
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
cIV Group iIV Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/30 (46.67%)      9/27 (33.33%)    
Cardiac disorders     
death  [1]  6/30 (20.00%)  6 3/27 (11.11%)  3
rehospitalization for all cardiovascular causes   8/30 (26.67%)  8 6/27 (22.22%)  6
Renal and urinary disorders     
needing renal replacement therapy   0/30 (0.00%)  0 0/27 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
Cardiac death
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
cIV Group iIV Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/30 (0.00%)      0/27 (0.00%)    
Our study didn't explain the reasons of renal dysfunction during treatment. Concurrent evaluation of BUN could further clarify the primary defect.The multivariate analysis could be inadequate for small sample; we intend to continue enrollment.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Alberto Palazzuoli MD, Cardiology Unit
Organization: Department of Internal Medicine, University of Siena, Le Scotte hospital, Siena, Italy
Phone: +39577585363
Responsible Party: Alberto Palazzuoli MD PhD, University of Siena
ClinicalTrials.gov Identifier: NCT01441245     History of Changes
Other Study ID Numbers: diuretic1
First Submitted: September 22, 2011
First Posted: September 27, 2011
Results First Submitted: January 26, 2015
Results First Posted: February 2, 2016
Last Update Posted: January 23, 2018