Heart Failure
Conditions
Keywords
Sodium Homeostasis
Brief summary
The purpose of this study is to understand the effects of chloride supplementation on volume-overloaded acute heart failure patients concomitantly treated with IV diuretics.
Detailed description
The overarching goal of this proposal is to develop a comprehensive understanding of the biology and therapeutic potential of sodium-free chloride supplementation. While sodium homeostasis has been the focus of substantial investigation, very little research has been devoted to understanding chloride homeostasis. Thus, this proposal is designed to obtain the full spectrum of information pertaining to chloride, such as novel areas with great interest by the scientific community (i.e. modulation of the WNK-kinase system and the use of exosomes), to more practical/basic questions (i.e. what happens to sodium chloride balance when a patient is challenged with chloride). The proposed outpatient study has been designed to serve as a real world efficacy study. With extensive biobanking and analysis of samples in the proposed setting, there is the potential to be able to deliver a great wealth of information on the biology and therapeutic potential of manipulating chloride homeostasis in heart failure. Research confirms that many heart failure therapies demonstrate measurable benefit in highly controlled environments, but lack effectiveness when studied in decompensated patients receiving standard decongestive therapies. As such, this study seeks to understand the effects of chloride supplementation on volume-overloaded patients concomitantly treated with IV diuretics.
Interventions
DRUGLysine Chloride
Patients will receive 7 days of therapy using 115 mmol/day of lysine chloride. Patients will be given the option of a taste test of both lysine chloride \& the placebo powders mixed with various beverages to ensure it is palatable to them. If the patient feels they will not be able to take the study medication twice a day due to taste, they will be withdrawn from the study at this time.
OTHERPlacebo
Patients will receive 7 days of therapy using placebo. Patients will be given the option of a taste test of both lysine chloride \& the placebo powders mixed with various beverages to ensure it is palatable to them. If the patient feels they will not be able to take the study medication twice a day due to taste, they will be withdrawn from the study at this time.
Sponsors
Yale University
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of decompensated heart failure with at least one objective sign of volume overload (rales, edema, elevated jugular venous pressure (JVP), or weight gain of at least 5 pounds) * A projected need by the treating clinician for continued treatment with IV diuretics * Chronic loop diuretic use
Exclusion criteria
* Inability to commit to or comply with serial visits for treatment in the Yale Transitional Care Center (YTCC) * History of severe metabolic or respiratory acidosis within 30 days of enrollment * Use of metformin, acetazolamide, or any other agent that could predispose to acidosis. Patients who are on metformin may be enrolled if their metformin can be discontinued safely for the duration of the study. Any participants who have consistently elevated Blood glucose readings \> 200 mg/dL while inpatient will not be enrolled. * Serum bicarbonate level \<20mmol/L * Estimated glomerular filtration rate \<20 mL/min or renal replacement therapy * Appears unlikely, or unable to participate in the required study procedures, as assessed by the study PI or research registered nurse (RN) (ex: clinically-significant psychiatric, addictive, or neurological disease) * Inability to give written informed consent or follow study protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Blood Volume | Daily for 7 days | Volumex is albumin labeled with the iodine isotope I-131 and is an FDA-approved method used to determine total blood volume. A linear mixed effect model will be used to analyze the trial with class variables of time and treatment group. Daily measures of blood collection will be compared across the 7 day collection period between intervention and placebo arms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Log NTpro-BNP | Daily for 7-days | N-terminal prohormone of brain natriuretic peptide (NTpro-BNP) is used to screen and diagnosis of acute congestive heart failure (CHF) and can be used to establish prognosis in heart failure. A linear mixed effect model will be used to analyze the trial with class variables of time and treatment group. Daily measures of NTpro-BNP will be compared across the 7 day collection period between intervention and placebo arms. |
| Change in Serum Creatinine | Daily for 7-days | A linear mixed effect model will be used to analyze the trial with class variables of time and treatment group. Daily measures of serum creatinine will be compared across the 7 day collection period between intervention and placebo arms. |
| Change in Cystatin C | Daily for 7-days | A linear mixed effect model will be used to analyze the trial with class variables of time and treatment group. Daily measures of cystatin C will be compared across the 7 day collection period between intervention and placebo arms. |
| Change in Chloride | Daily for 7-days | A linear mixed effect model will be used to analyze the trial with class variables of time and treatment group. Daily measures of chloride will be compared across the 7 day collection period between intervention and placebo arms. |
| Change in Bicarbonate | Daily for 7-days | A linear mixed effect model will be used to analyze the trial with class variables of time and treatment group. Daily measures of bicarbonate will be compared across the 7 day collection period between intervention and placebo arms. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lysine Chloride Participants will be randomized to 7 days of therapy with either 115 mmol/day of lysine chloride or placebo. People in the Lysine Chloride group will receive the active intervention.
Lysine Chloride: Patients will receive 7 days of therapy using 115 mmol/day of lysine chloride. Patients will be given the option of a taste test of both lysine chloride & the placebo powders mixed with various beverages to ensure it is palatable to them. If the patient feels they will not be able to take the study medication twice a day due to taste, they will be withdrawn from the study at this time. | 22 |
| Placebo Participants will be randomized to 7 days of therapy with either 115 mmol/day of lysine chloride or placebo. People in the Placebo group will receive placebo.
Placebo: Patients will receive 7 days of therapy using placebo. Patients will be given the option of a taste test of both lysine chloride & the placebo powders mixed with various beverages to ensure it is palatable to them. If the patient feels they will not be able to take the study medication twice a day due to taste, they will be withdrawn from the study at this time. | 18 |
| Total | 40 |
Baseline characteristics
| Characteristic | Placebo | Total | Lysine Chloride |
|---|---|---|---|
| Age, Continuous | 58.61 years STANDARD_DEVIATION 13.68 | 56.30 years STANDARD_DEVIATION 13.63 | 54.4 years STANDARD_DEVIATION 13.61 |
| Diastolic blood pressure | 78.0 mmHg STANDARD_DEVIATION 15.43 | 74.47 mmHg STANDARD_DEVIATION 13.31 | 71.59 mmHg STANDARD_DEVIATION 10.82 |
| Heart rate | 88.11 bpm STANDARD_DEVIATION 21.61 | 83.80 bpm STANDARD_DEVIATION 19.33 | 80.27 bpm STANDARD_DEVIATION 16.93 |
| Race/Ethnicity, Customized Race Black | 8 Participants | 18 Participants | 10 Participants |
| Race/Ethnicity, Customized Race Other | 2 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 8 Participants | 19 Participants | 11 Participants |
| Region of Enrollment United States | 18 participants | 40 participants | 22 participants |
| Sex: Female, Male Female | 5 Participants | 11 Participants | 6 Participants |
| Sex: Female, Male Male | 13 Participants | 29 Participants | 16 Participants |
| Systolic blood pressure | 129.44 mmHg STANDARD_DEVIATION 28.03 | 124.43 mmHg STANDARD_DEVIATION 26.28 | 120.32 mmHg STANDARD_DEVIATION 24.66 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 18 |
| other Total, other adverse events | 12 / 22 | 5 / 18 |
| serious Total, serious adverse events | 0 / 22 | 0 / 18 |
Outcome results
Primary
Change in Blood Volume
Volumex is albumin labeled with the iodine isotope I-131 and is an FDA-approved method used to determine total blood volume. A linear mixed effect model will be used to analyze the trial with class variables of time and treatment group. Daily measures of blood collection will be compared across the 7 day collection period between intervention and placebo arms.
Time frame: Daily for 7 days
Population: Intention to treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lysine Chloride | Change in Blood Volume | -320 mL | Standard Deviation 689 |
| Placebo | Change in Blood Volume | -447 mL | Standard Deviation 520 |
p-value: 0.56t-test, 2 sided
Secondary
Change in Bicarbonate
A linear mixed effect model will be used to analyze the trial with class variables of time and treatment group. Daily measures of bicarbonate will be compared across the 7 day collection period between intervention and placebo arms.
Time frame: Daily for 7-days
Population: Intention to treat
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Lysine Chloride | Change in Bicarbonate | -1.02 mmol/L per day |
| Placebo | Change in Bicarbonate | 0.19 mmol/L per day |
p-value: <0.001t-test, 2 sided
Secondary
Change in Chloride
A linear mixed effect model will be used to analyze the trial with class variables of time and treatment group. Daily measures of chloride will be compared across the 7 day collection period between intervention and placebo arms.
Time frame: Daily for 7-days
Population: Intention to treat
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Lysine Chloride | Change in Chloride | 0.71 mmol/L per day |
| Placebo | Change in Chloride | -0.87 mmol/L per day |
p-value: <0.001t-test, 2 sided
Secondary
Change in Cystatin C
A linear mixed effect model will be used to analyze the trial with class variables of time and treatment group. Daily measures of cystatin C will be compared across the 7 day collection period between intervention and placebo arms.
Time frame: Daily for 7-days
Secondary
Change in Log NTpro-BNP
N-terminal prohormone of brain natriuretic peptide (NTpro-BNP) is used to screen and diagnosis of acute congestive heart failure (CHF) and can be used to establish prognosis in heart failure. A linear mixed effect model will be used to analyze the trial with class variables of time and treatment group. Daily measures of NTpro-BNP will be compared across the 7 day collection period between intervention and placebo arms.
Time frame: Daily for 7-days
Secondary
Change in Serum Creatinine
A linear mixed effect model will be used to analyze the trial with class variables of time and treatment group. Daily measures of serum creatinine will be compared across the 7 day collection period between intervention and placebo arms.
Time frame: Daily for 7-days
Population: Intention to treat
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Lysine Chloride | Change in Serum Creatinine | 0.00 mg/dL per day |
| Placebo | Change in Serum Creatinine | 0.04 mg/dL per day |
p-value: 0.039t-test, 2 sided