A Phase 1/2 interventional study of Furosemide in Heart Failure and Kidney Dysfunction, sponsored by Mayo Clinic. Completed at 1 site in United States. Open to participants aged 18 Years to 90 Years. Per ClinicalTrials.gov, last updated 2015-07-20.
Sponsored by Mayo Clinic · Phase 1/2, Interventional, and Treatment
The investigators' objective is to define the effects of decreasing the furosemide dose on heart, kidney and humoral function in people with compensated heart failure and kidney dysfunction and also in people with compensated heart failure without kidney dysfunction. Secondly, to define the humoral activation in both groups.
The broad objective of this protocol is to advance our understanding of the pathophysiological mechanisms of human Cardiorenal Syndrome (CRS) with a specific emphasis upon the biological interaction between diuretic therapy, the renin-angiotensin-aldosterone-system (RAAS) and cyclic 3'-5'-guanosine monophosphate (cGMP) pathway.
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Inclusion Criteria for Subjects with Compensated CHF without Renal Dysfunction:
Inclusion Criteria for Subjects with Compensated CHF with Renal Dysfunction:
Exclusion Criteria for both groups:
Subjects received their clinically prescribed dose of furosemide for a 3 week stabilization period, then were assessed for cardiorenal and humoral function. Subjects then had a 50% reduction of the furosemide dose for a 3 week stabilization period, and were assessed for cardiorenal and humoral function again.
Drug: Furosemide
Subjects received their clinically prescribed dose of furosemide for a 3 week stabilization period, then were assessed for cardiorenal and humoral function. Subjects then had a 50% reduction of the furosemide dose for a 3 week stabilization period, and were assessed for cardiorenal and humoral function again.
Also known as: Lasix
Renal Function as Measured by Glomerular Filtration Rate (GFR) at Baseline and in Response to Decreasing Furosemide Dose
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
Renal Plasma Flow at Baseline and in Response to Decreasing Furosemide Dose
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
Aldosterone at Baseline and in Response to Decreasing Furosemide Dose
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
Plasma Renin Activity at Baseline and in Response to Decreasing Furosemide Dose
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
Angiotensin II at Baseline and in Response to Decreasing Furosemide Dose
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
Plasma Cyclic Guanosine Monophosphate (cGMP) at Baseline and in Response to Decreasing Furosemide Dose
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
Subjects were recruited from outpatients being treated at the Mayo Clinic in Rochester, Minnesota.
| Milestone | Compensated CHF Without Renal Dysfunction | Compensated CHF With Renal Dysfunction |
|---|---|---|
| Started | 13 | 19 |
| Completed | 13 | 19 |
| Not completed | 0 | 0 |
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.
| ml/min | Compensated CHF Without Renal Dysfunction | Compensated CHF With Renal Dysfunction |
|---|---|---|
| Baseline (3 weeks) | 77 ± 3 | 42 ± 3 |
| Approximately 6 weeks | 73 ± 5 | 50 ± 4 |
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.
| ml/min | Compensated CHF Without Renal Dysfunction | Compensated CHF With Renal Dysfunction |
|---|---|---|
| Baseline (3 weeks) | 304 ± 19 | 198 ± 20 |
| Approximately 6 weeks | 293 ± 23 | 214 ± 21 |
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.
| ng/dL | Compensated CHF Without Renal Dysfunction | Compensated CHF With Renal Dysfunction |
|---|---|---|
| Baseline (3 weeks) | 7.9 ± 1.8 | 4.9 ± 0.6 |
| Approximately 6 weeks | 7.6 ± 1.3 | 4.9 ± 0.6 |
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.
| ng/mL/hr | Compensated CHF Without Renal Dysfunction | Compensated CHF With Renal Dysfunction |
|---|---|---|
| Baseline (3 weeks) | 4.3 ± 2.0 | 2.1 ± 0.8 |
| Approximately 6 weeks | 2.7 ± 1.1 | 1.4 ± 0.5 |
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.
| pg/mL | Compensated CHF Without Renal Dysfunction | Compensated CHF With Renal Dysfunction |
|---|---|---|
| Baseline (3 weeks) | 3.3 ± 0.6 | 3.1 ± 0.7 |
| Approximately 6 weeks | 3.4 ± 1.0 | 3.2 ± 0.9 |
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.
| pg/mL | Compensated CHF Without Renal Dysfunction | Compensated CHF With Renal Dysfunction |
|---|---|---|
| Baseline (3 weeks) | 5.0 ± 0.9 | 5.7 ± 0.8 |
| Approximately 6 weeks | 4.6 ± 0.7 | 7.0 ± 1.0 |
Collected over 6 weeks. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Compensated CHF Without Renal Dysfunction | — | 0/13 (0%) | 0/13 (0%) |
| Compensated CHF With Renal Dysfunction | — | 2/19 (10.5%) | 1/19 (5.3%) |
| Event | Compensated CHF Without Renal Dysfunction | Compensated CHF With Renal Dysfunction |
|---|---|---|
| HyperkalemiaRenal and urinary disorders | 0/13 | 1/19 |
| Chest painCardiac disorders | 0/13 | 1/19 |
| Event | Compensated CHF Without Renal Dysfunction | Compensated CHF With Renal Dysfunction |
|---|---|---|
| DysuriaRenal and urinary disorders | 0/13 | 1/19 |
| Age, Continuous(years) | Compensated CHF Without Renal Dysfunction | Compensated CHF With Renal Dysfunction | Total |
|---|---|---|---|
| Mean | 68 ± 3 | 76 ± 2 | 72.7 ± 9.6 |
| Sex: Female, Male(Participants) | Compensated CHF Without Renal Dysfunction | Compensated CHF With Renal Dysfunction | Total |
|---|---|---|---|
| Female | 4 | 6 | 10 |
| Male | 9 | 13 | 22 |
| Region of Enrollment(participants) | Compensated CHF Without Renal Dysfunction | Compensated CHF With Renal Dysfunction | Total |
|---|---|---|---|
| United States | 13 | 19 | 32 |
This study is completed, as verified in Jun 2015. You cannot join it, but the record below documents what was studied.
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