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| ID | Type | Description | Link |
|---|---|---|---|
| R01HL084155 | U.S. NIH Grant/Contract | View source | |
| P01HL076611 | U.S. NIH Grant/Contract | View source | |
| UL1TR000135 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Furosemide | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Furosemide | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 3 weeks, approximately 6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 3 weeks, approximately 6 weeks |
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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:
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| Name | Affiliation | Role |
|---|---|---|
| Horng H Chen, MD | Mayo Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25262369 | Result | McKie PM, Schirger JA, Benike SL, Harstad LK, Chen HH. The effects of dose reduction of furosemide on glomerular filtration rate in stable systolic heart failure. JACC Heart Fail. 2014 Dec;2(6):675-7. doi: 10.1016/j.jchf.2014.05.014. Epub 2014 Sep 24. No abstract available. |
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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.
Subjects were recruited from outpatients being treated at the Mayo Clinic in Rochester, Minnesota.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | Compensated CHF With Renal Dysfunction | Renal Dysfunction was defined as GFR less than 60 mg/min/1.73m^2. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Compensated CHF Without Renal Dysfunction | Preserved renal function was defined as GFR greater than or equal to 60 mg/min/1.73m^2. |
| BG001 | Compensated CHF With Renal Dysfunction |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | 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. | Posted | Mean | Standard Deviation | ml/min | 3 weeks, approximately 6 weeks |
|
6 weeks
Subjects received weekly phone calls from the study coordinator to address any concerns and to collect safety information.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hyperkalemia | Renal and urinary disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dysuria | Renal and urinary disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Horng Chen | Mayo Clinic | 507-538-2354 | chen.horng@mayo.edu |
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| ID | Term |
|---|---|
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D005665 | Furosemide |
| ID | Term |
|---|---|
| D013424 | Sulfanilamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
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|
|
| 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. | 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. | 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. | 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. | 3 weeks, approximately 6 weeks |
Renal Dysfunction was defined as GFR less than 60 mg/min/1.73m^2.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Renal Dysfunction was defined as GFR less than 60 mg/min/1.73m^2. |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | ml/min | 3 weeks, approximately 6 weeks |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | ng/dL | 3 weeks, approximately 6 weeks |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | ng/mL/hr | 3 weeks, approximately 6 weeks |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | pg/mL | 3 weeks, approximately 6 weeks |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | pg/mL | 3 weeks, approximately 6 weeks |
|
|
|
|
| 0 |
| 13 |
| 0 |
| 13 |
| EG001 | Compensated CHF With Renal Dysfunction | Renal Dysfunction was defined as GFR less than 60 mg/min/1.73m^2. | 2 | 19 | 1 | 19 |
| Chest pain | Cardiac disorders | Systematic Assessment |
|
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| D000814 |
| Aniline Compounds |
| D000588 | Amines |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |