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The Effects of Decreasing the Lasix Dose on the Cardiorenal System (Aim1)

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ClinicalTrials.gov Identifier: NCT00982423
Recruitment Status : Completed
First Posted : September 23, 2009
Results First Posted : July 20, 2015
Last Update Posted : July 20, 2015
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Horng Chen, Mayo Clinic

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Heart Failure
Kidney Dysfunction
Intervention Drug: Furosemide
Enrollment 41
Recruitment Details Subjects were recruited from outpatients being treated at the Mayo Clinic in Rochester, Minnesota.
Pre-assignment Details There was 1 screen failure and 8 subjects withdrew prior to group assignment: 1 due to chest pain, 1 due to surgical procedure scheduled to take place during treatment phase, 1 due to fluid overload, 2 due to time constraints of work and family issues, and 3 due to primary physician-initiated medication titration.
Arm/Group Title Compensated CHF Without Renal Dysfunction Compensated CHF With Renal Dysfunction
Hide Arm/Group Description Preserved renal function was defined as glomerular filtration rate (GFR) greater than or equal to 60 mg/min/1.73m^2. Renal Dysfunction was defined as GFR less than 60 mg/min/1.73m^2.
Period Title: Overall Study
Started 13 19
Completed 13 19
Not Completed 0 0
Arm/Group Title Compensated CHF Without Renal Dysfunction Compensated CHF With Renal Dysfunction Total
Hide Arm/Group Description Preserved renal function was defined as GFR greater than or equal to 60 mg/min/1.73m^2. Renal Dysfunction was defined as GFR less than 60 mg/min/1.73m^2. Total of all reporting groups
Overall Number of Baseline Participants 13 19 32
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 13 participants 19 participants 32 participants
68  (3) 76  (2) 72.7  (9.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 13 participants 19 participants 32 participants
Female
4
  30.8%
6
  31.6%
10
  31.3%
Male
9
  69.2%
13
  68.4%
22
  68.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 13 participants 19 participants 32 participants
13 19 32
1.Primary Outcome
Title Renal Function as Measured by Glomerular Filtration Rate (GFR) at Baseline and in Response to Decreasing Furosemide Dose
Hide Description Kidney function was measured by GFR determined by iothalamate clearance. GFR describes the flow rate of filtered fluid through the kidney measured in milliliters per minute per 1.73 m^2 of body surface area. A lower GFR means the kidney is not filtering normally. An estimated GFR of less than 60 mg/min/1.73 m^2 of body surface area is considered to be impaired kidney function.
Time Frame 3 weeks, approximately 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Compensated CHF Without Renal Dysfunction Compensated CHF With Renal Dysfunction
Hide Arm/Group Description:
Preserved renal function was defined as glomerular filtration rate (GFR) greater than or equal to 60 mg/min/1.73m^2.
Renal Dysfunction was defined as GFR less than 60 mg/min/1.73m^2.
Overall Number of Participants Analyzed 13 19
Mean (Standard Deviation)
Unit of Measure: ml/min
Baseline (3 weeks) 77  (3) 42  (3)
Approximately 6 weeks 73  (5) 50  (4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Compensated CHF With Renal Dysfunction
Comments Comparison between baseline dose of furosemide (3 weeks) versus reduced dose of furosemide (approximately 6 weeks).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
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 Compensated CHF With Renal Dysfunction
Comments Comparison between GFR taken at baseline dose Furosemide (3 weeks) versus normal GFR
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method t-test, 1 sided
Comments [Not Specified]
2.Secondary Outcome
Title Renal Plasma Flow at Baseline and in Response to Decreasing Furosemide Dose
Hide Description Effective renal plasma flow (eRPF) is a measure used to calculate renal plasma flow (RPF) and hence estimate renal function. Renal plasma flow is the volume of blood plasma that flows through the kidneys per unit time, measured as ml/min.
Time Frame 3 weeks, approximately 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Compensated CHF Without Renal Dysfunction Compensated CHF With Renal Dysfunction
Hide Arm/Group Description:
Preserved renal function was defined as glomerular filtration rate (GFR) greater than or equal to 60 mg/min/1.73m^2.
Renal Dysfunction was defined as GFR less than 60 mg/min/1.73m^2.
Overall Number of Participants Analyzed 13 19
Mean (Standard Deviation)
Unit of Measure: ml/min
Baseline (3 weeks) 304  (19) 198  (20)
Approximately 6 weeks 293  (23) 214  (21)
3.Secondary Outcome
Title Aldosterone at Baseline and in Response to Decreasing Furosemide Dose
Hide Description Aldosterone is part of the renin–angiotensin-aldosterone system (RAAS). Drugs that interfere with the secretion or action of aldosterone are in use as antihypertensives, like lisinopril, which lowers blood pressure by blocking the angiotensin-converting enzyme (ACE), leading to lower aldosterone secretion. The net effect of these drugs is to reduce sodium and water retention but increase retention of potassium.
Time Frame 3 weeks, approximately 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Compensated CHF Without Renal Dysfunction Compensated CHF With Renal Dysfunction
Hide Arm/Group Description:
Preserved renal function was defined as GFR greater than or equal to 60 mg/min/1.73m^2.
Renal Dysfunction was defined as GFR less than 60 mg/min/1.73m^2.
Overall Number of Participants Analyzed 13 19
Mean (Standard Deviation)
Unit of Measure: ng/dL
Baseline (3 weeks) 7.9  (1.8) 4.9  (0.6)
Approximately 6 weeks 7.6  (1.3) 4.9  (0.6)
4.Secondary Outcome
Title Plasma Renin Activity at Baseline and in Response to Decreasing Furosemide Dose
Hide Description Plasma renin activity is a measure of the activity of the plasma enzyme renin, which plays a major role in the body's regulation of blood pressure, thirst, and urine output. Renin is an enzyme that hydrolyses angiotensinogen secreted from the liver into the peptide angiotensin I. Renin's primary function is to cause an increase in blood pressure, leading to restoration of perfusion pressure in the kidneys.
Time Frame 3 weeks, approximately 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Compensated CHF Without Renal Dysfunction Compensated CHF With Renal Dysfunction
Hide Arm/Group Description:
Preserved renal function was defined as GFR greater than or equal to 60 mg/min/1.73m^2.
Renal Dysfunction was defined as GFR less than 60 mg/min/1.73m^2.
Overall Number of Participants Analyzed 13 19
Mean (Standard Deviation)
Unit of Measure: ng/mL/hr
Baseline (3 weeks) 4.3  (2.0) 2.1  (0.8)
Approximately 6 weeks 2.7  (1.1) 1.4  (0.5)
5.Secondary Outcome
Title Angiotensin II at Baseline and in Response to Decreasing Furosemide Dose
Hide Description Renin activates the renin-angiotensin system by cleaving angiotensinogen, produced by the liver, to yield angiotensin I, which is further converted into angiotensin II by the angiotensin-converting enzyme (ACE) primarily within the capillaries of the lungs. Angiotensin II then constricts blood vessels, increases the secretion of antidiuretic hormone (ADH) and aldosterone, and stimulates the hypothalamus to activate the thirst reflex, each leading to an increase in blood pressure.
Time Frame 3 weeks, approximately 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Compensated CHF Without Renal Dysfunction Compensated CHF With Renal Dysfunction
Hide Arm/Group Description:
Preserved renal function was defined as GFR greater than or equal to 60 mg/min/1.73m^2.
Renal Dysfunction was defined as GFR less than 60 mg/min/1.73m^2.
Overall Number of Participants Analyzed 13 19
Mean (Standard Deviation)
Unit of Measure: pg/mL
Baseline (3 weeks) 3.3  (0.6) 3.1  (0.7)
Approximately 6 weeks 3.4  (1.0) 3.2  (0.9)
6.Secondary Outcome
Title Plasma Cyclic Guanosine Monophosphate (cGMP) at Baseline and in Response to Decreasing Furosemide Dose
Hide Description Any change in atrial filling pressures leads to the release of atrial natriuretic peptides (ANP) from the heart. Once released, atrial peptides exert potent direct vasodilator and natriuretic actions by virtue of the ability to increase their intracellular second messenger, cGMP. Plasma cGMP correlates closely with the severity of congestive heart failure.
Time Frame 3 weeks, approximately 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Compensated CHF Without Renal Dysfunction Compensated CHF With Renal Dysfunction
Hide Arm/Group Description:
Preserved renal function was defined as GFR greater than or equal to 60 mg/min/1.73m^2.
Renal Dysfunction was defined as GFR less than 60 mg/min/1.73m^2.
Overall Number of Participants Analyzed 13 19
Mean (Standard Deviation)
Unit of Measure: pg/mL
Baseline (3 weeks) 5.0  (0.9) 5.7  (0.8)
Approximately 6 weeks 4.6  (0.7) 7.0  (1.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Compensated CHF With Renal Dysfunction
Comments Comparison between reduced dose Furosemide and baseline dose Furosemide
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.075
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Time Frame 6 weeks
Adverse Event Reporting Description Subjects received weekly phone calls from the study coordinator to address any concerns and to collect safety information.
 
Arm/Group Title Compensated CHF Without Renal Dysfunction Compensated CHF With Renal Dysfunction
Hide Arm/Group Description Preserved renal function was defined as glomerular filtration rate (GFR) greater than or equal to 60 mg/min/1.73m^2. Renal Dysfunction was defined as GFR less than 60 mg/min/1.73m^2.
All-Cause Mortality
Compensated CHF Without Renal Dysfunction Compensated CHF With Renal Dysfunction
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Compensated CHF Without Renal Dysfunction Compensated CHF With Renal Dysfunction
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/13 (0.00%)      2/19 (10.53%)    
Cardiac disorders     
Chest pain   0/13 (0.00%)  0 1/19 (5.26%)  1
Renal and urinary disorders     
Hyperkalemia   0/13 (0.00%)  0 1/19 (5.26%)  1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Compensated CHF Without Renal Dysfunction Compensated CHF With Renal Dysfunction
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/13 (0.00%)      1/19 (5.26%)    
Renal and urinary disorders     
Dysuria   0/13 (0.00%)  0 1/19 (5.26%)  1
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Horng Chen
Organization: Mayo Clinic
Phone: 507-538-2354
EMail: chen.horng@mayo.edu
Layout table for additonal information
Responsible Party: Horng Chen, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00982423     History of Changes
Other Study ID Numbers: 09-003210
R01HL084155 ( U.S. NIH Grant/Contract )
P01HL076611 ( U.S. NIH Grant/Contract )
UL1TR000135 ( U.S. NIH Grant/Contract )
First Submitted: September 18, 2009
First Posted: September 23, 2009
Results First Submitted: June 22, 2015
Results First Posted: July 20, 2015
Last Update Posted: July 20, 2015