Trial Outcomes & Findings for The Effects of Decreasing the Lasix Dose on the Cardiorenal System (NCT NCT00982423)

NCT ID: NCT00982423

Last Updated: 2015-07-20

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 41 participants
• Primary outcome timeframe: 3 weeks, approximately 6 weeks
• Results posted on: 2015-07-20

Participant Flow

Subjects were recruited from outpatients being treated at the Mayo Clinic in Rochester, Minnesota.

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.

Participant milestones

Measure	Compensated CHF Without Renal Dysfunction Preserved renal function was defined as glomerular filtration rate (GFR) greater than or equal to 60 mg/min/1.73m\^2.	Compensated CHF With Renal Dysfunction Renal Dysfunction was defined as GFR less than 60 mg/min/1.73m\^2.
Overall Study STARTED	13	19
Overall Study COMPLETED	13	19
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

The Effects of Decreasing the Lasix Dose on the Cardiorenal System

Baseline characteristics by cohort

Measure	Compensated CHF Without Renal Dysfunction n=13 Participants Preserved renal function was defined as GFR greater than or equal to 60 mg/min/1.73m\^2.	Compensated CHF With Renal Dysfunction n=19 Participants Renal Dysfunction was defined as GFR less than 60 mg/min/1.73m\^2.	Total n=32 Participants Total of all reporting groups
Age, Continuous	68 years STANDARD_DEVIATION 3 • n=5 Participants	76 years STANDARD_DEVIATION 2 • n=7 Participants	72.7 years STANDARD_DEVIATION 9.6 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	13 Participants n=7 Participants	22 Participants n=5 Participants
Region of Enrollment United States	13 participants n=5 Participants	19 participants n=7 Participants	32 participants n=5 Participants

PRIMARY outcome

Timeframe: 3 weeks, approximately 6 weeks

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.

Outcome measures

Measure	Compensated CHF Without Renal Dysfunction n=13 Participants Preserved renal function was defined as glomerular filtration rate (GFR) greater than or equal to 60 mg/min/1.73m\^2.	Compensated CHF With Renal Dysfunction n=19 Participants Renal Dysfunction was defined as GFR less than 60 mg/min/1.73m\^2.
Renal Function as Measured by Glomerular Filtration Rate (GFR) at Baseline and in Response to Decreasing Furosemide Dose Baseline (3 weeks)	77 ml/min Standard Deviation 3	42 ml/min Standard Deviation 3
Renal Function as Measured by Glomerular Filtration Rate (GFR) at Baseline and in Response to Decreasing Furosemide Dose Approximately 6 weeks	73 ml/min Standard Deviation 5	50 ml/min Standard Deviation 4

SECONDARY outcome

Timeframe: 3 weeks, approximately 6 weeks

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.

Outcome measures

Measure	Compensated CHF Without Renal Dysfunction n=13 Participants Preserved renal function was defined as glomerular filtration rate (GFR) greater than or equal to 60 mg/min/1.73m\^2.	Compensated CHF With Renal Dysfunction n=19 Participants Renal Dysfunction was defined as GFR less than 60 mg/min/1.73m\^2.
Renal Plasma Flow at Baseline and in Response to Decreasing Furosemide Dose Baseline (3 weeks)	304 ml/min Standard Deviation 19	198 ml/min Standard Deviation 20
Renal Plasma Flow at Baseline and in Response to Decreasing Furosemide Dose Approximately 6 weeks	293 ml/min Standard Deviation 23	214 ml/min Standard Deviation 21

SECONDARY outcome

Timeframe: 3 weeks, approximately 6 weeks

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.

Outcome measures

Measure	Compensated CHF Without Renal Dysfunction n=13 Participants Preserved renal function was defined as glomerular filtration rate (GFR) greater than or equal to 60 mg/min/1.73m\^2.	Compensated CHF With Renal Dysfunction n=19 Participants Renal Dysfunction was defined as GFR less than 60 mg/min/1.73m\^2.
Aldosterone at Baseline and in Response to Decreasing Furosemide Dose Baseline (3 weeks)	7.9 ng/dL Standard Deviation 1.8	4.9 ng/dL Standard Deviation 0.6
Aldosterone at Baseline and in Response to Decreasing Furosemide Dose Approximately 6 weeks	7.6 ng/dL Standard Deviation 1.3	4.9 ng/dL Standard Deviation 0.6

SECONDARY outcome

Timeframe: 3 weeks, approximately 6 weeks

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.

Outcome measures

Measure	Compensated CHF Without Renal Dysfunction n=13 Participants Preserved renal function was defined as glomerular filtration rate (GFR) greater than or equal to 60 mg/min/1.73m\^2.	Compensated CHF With Renal Dysfunction n=19 Participants Renal Dysfunction was defined as GFR less than 60 mg/min/1.73m\^2.
Plasma Renin Activity at Baseline and in Response to Decreasing Furosemide Dose Baseline (3 weeks)	4.3 ng/mL/hr Standard Deviation 2.0	2.1 ng/mL/hr Standard Deviation 0.8
Plasma Renin Activity at Baseline and in Response to Decreasing Furosemide Dose Approximately 6 weeks	2.7 ng/mL/hr Standard Deviation 1.1	1.4 ng/mL/hr Standard Deviation 0.5

SECONDARY outcome

Timeframe: 3 weeks, approximately 6 weeks

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.

Outcome measures

Measure	Compensated CHF Without Renal Dysfunction n=13 Participants Preserved renal function was defined as glomerular filtration rate (GFR) greater than or equal to 60 mg/min/1.73m\^2.	Compensated CHF With Renal Dysfunction n=19 Participants Renal Dysfunction was defined as GFR less than 60 mg/min/1.73m\^2.
Angiotensin II at Baseline and in Response to Decreasing Furosemide Dose Baseline (3 weeks)	3.3 pg/mL Standard Deviation 0.6	3.1 pg/mL Standard Deviation 0.7
Angiotensin II at Baseline and in Response to Decreasing Furosemide Dose Approximately 6 weeks	3.4 pg/mL Standard Deviation 1.0	3.2 pg/mL Standard Deviation 0.9

SECONDARY outcome

Timeframe: 3 weeks, approximately 6 weeks

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.

Outcome measures

Measure	Compensated CHF Without Renal Dysfunction n=13 Participants Preserved renal function was defined as glomerular filtration rate (GFR) greater than or equal to 60 mg/min/1.73m\^2.	Compensated CHF With Renal Dysfunction n=19 Participants Renal Dysfunction was defined as GFR less than 60 mg/min/1.73m\^2.
Plasma Cyclic Guanosine Monophosphate (cGMP) at Baseline and in Response to Decreasing Furosemide Dose Baseline (3 weeks)	5.0 pg/mL Standard Deviation 0.9	5.7 pg/mL Standard Deviation 0.8
Plasma Cyclic Guanosine Monophosphate (cGMP) at Baseline and in Response to Decreasing Furosemide Dose Approximately 6 weeks	4.6 pg/mL Standard Deviation 0.7	7.0 pg/mL Standard Deviation 1.0

Adverse Events

Compensated CHF Without Renal Dysfunction

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Compensated CHF With Renal Dysfunction

Serious events: 2 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Compensated CHF Without Renal Dysfunction n=13 participants at risk Preserved renal function was defined as glomerular filtration rate (GFR) greater than or equal to 60 mg/min/1.73m\^2.	Compensated CHF With Renal Dysfunction n=19 participants at risk Renal Dysfunction was defined as GFR less than 60 mg/min/1.73m\^2.
Renal and urinary disorders Hyperkalemia	0.00% 0/13 • 6 weeks Subjects received weekly phone calls from the study coordinator to address any concerns and to collect safety information.	5.3% 1/19 • Number of events 1 • 6 weeks Subjects received weekly phone calls from the study coordinator to address any concerns and to collect safety information.
Cardiac disorders Chest pain	0.00% 0/13 • 6 weeks Subjects received weekly phone calls from the study coordinator to address any concerns and to collect safety information.	5.3% 1/19 • Number of events 1 • 6 weeks Subjects received weekly phone calls from the study coordinator to address any concerns and to collect safety information.

Other adverse events

Measure	Compensated CHF Without Renal Dysfunction n=13 participants at risk Preserved renal function was defined as glomerular filtration rate (GFR) greater than or equal to 60 mg/min/1.73m\^2.	Compensated CHF With Renal Dysfunction n=19 participants at risk Renal Dysfunction was defined as GFR less than 60 mg/min/1.73m\^2.
Renal and urinary disorders Dysuria	0.00% 0/13 • 6 weeks Subjects received weekly phone calls from the study coordinator to address any concerns and to collect safety information.	5.3% 1/19 • Number of events 1 • 6 weeks Subjects received weekly phone calls from the study coordinator to address any concerns and to collect safety information.

Additional Information

Dr. Horng Chen

Mayo Clinic

Phone: 507-538-2354

Email: chen.horng@mayo.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place