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This is a randomized trial of protocolized diuretic therapy guided by urinary sodium compared to structured usual care in ED patients with AHF. Participants will be recruited following an initial standard evaluation in the ED and randomized in a 1:1 fashion to structured usual care or protocolized diuretic therapy guided by urinary sodium.
A standardized protocol driven treatment pathway for hospitalized patients started in the first few hours of ED evaluation and utilizing objective measures of diuretic response is needed. The investigators believe this would maximize diuretic efficiency, facilitate quicker resolution of congestion, avoid WHF and prolonged LOS, and reduce AHF readmissions. Propr data suggests low urine sodium predicts length of stay and outcomes after initial diuretic dosing in the outpatient and inpatient setting. Further, use of our pathway using spot urine sodium to titrate subsequent loop diuretic doses and maximize response in inpatients with AHF has shown compelling improvements in congestion and weight loss. However, a randomized trial is necessary to determine if initiating this protocol ,started in the ED, will improve AHF outcomes relative to structured usual care. Specifically, the investigators hypothesize use of spot urine sodium guided diuretic therapy will result in significant improvement in days of benefit over the 14 days after randomization. Days of benefit combines patient symptoms captured by global clinical status with clinical state quantifying the need for hospitalization and IV diuresis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Protocolized spot urine sodium guided diuretic therapy | Active Comparator | Patients will have a spot urine sodium and urine creatinine obtained. The urine and creatinine results will be input into the diuretic calculator and the diuretic dose will be chosen based on daily goals for urine output and net negative fluid balance. Performed 3 times per day, diuretic dosing will be individualized based on the proportion of 24-hour diuresis achieved since the prior IV diuretic dose. Every 24 hours new goals for urine output and net negative fluid balance are established based on the study and treatment team's assessment of residual congestion until protocol completion. |
|
| Guideline-based care | No Intervention | Patients will be placed on guideline-based diuretic dosing consistent with usual practice. The initial dose will be two times their home dose and will be subsequently adjusted by the treating team based on renal function and symptom severity. The treating team can increase or decrease the frequency and dose of diuretic based on urine output and clinical assessment. Patients in this arm also have urine collected 3 times per day by the bedside nurse to mirror the intervention arm. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Protocolized diuretic therapy | Drug | The urine sodium, urine creatinine and serum creatinine results will be input into the diuretic calculator and the diuretic dose will be chosen based on daily goals for urine output and net negative fluid balance. |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Status Score | Daily composite of the clinical state and global clinical status (GCS), expressed as an integer ranging in value from 0 (deceased) to 15 (outpatient; best possible GCS). | From the time of randomization through day 14 |
| Measure | Description | Time Frame |
|---|---|---|
| Inpatient clinical congestion | Daily orthodema score | from the time of randomization through the end of protocolized IV diuretics, approximately 14 days |
| Cardiorenal Death and AHF Readmission | Cardiorenal death and Acute Heart Failure Readmission |
| Measure | Description | Time Frame |
|---|---|---|
| Dyspnea score | measured daily using a continuous scale from 1-100 | from the time of randomization through the end of protocolized IV diuretics, approximately 14 days |
| Change in Kidney injury biomarkers |
Inclusion Criteria:
Age > 18
Emergency Department diagnosis of Acute Heart Failure (AHF)
Any one of the following:
i. Chest radiograph or lung ultrasound consistent with AHF ii. Jugular venous distension iii. Pulmonary rales on auscultation iv. Lower extremity edema v. S3 gallop
> 10 pounds of volume overload physician estimate or historical dry weight
IV diuretic ordered or planned to be during first 24 hours of ED or inpatient stay
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sean P. Collins, MD | Vanderbilt University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| VA Tennessee Valley Health Service | Nashville | Tennessee | 37232 | United States | ||
| Vanderbilt University Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38447632 | Derived | Mullens W, Martens P. Contemporary Diuretic Therapies for Acute Heart Failure: Time for a Desalination-Guided Approach? J Card Fail. 2024 May;30(5):737-738. doi: 10.1016/j.cardfail.2024.01.013. Epub 2024 Mar 4. No abstract available. | |
| 37544492 | Derived | Cox ZL, Siddiqi HK, Stevenson LW, Bales B, Han JH, Hart K, Imhoff B, Ivey-Miranda JB, Jenkins CA, Lindenfeld J, Shotwell MS, Miller KF, Ooi H, Rao VS, Schlendorf K, Self WH, Siew ED, Storrow A, Walsh R, Wrenn JO, Testani JM, Collins SP. Randomized controlled trial of urinE chemiStry guided aCute heArt faiLure treATmEnt (ESCALATE): Rationale and design. Am Heart J. 2023 Nov;265:121-131. doi: 10.1016/j.ahj.2023.07.014. Epub 2023 Aug 6. |
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The Publication Committee will authorize access to study data. Investigators must submit a proposal requesting approval to access our trial data. Our trial will participate in the NHLBI Central Repository for study data and specimens.
All data access will follow guidelines described in the NHLBI Limited Access Data Policy.
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The Publication Committee will authorize access to study data. Investigators must submit a proposal requesting approval to access our trial data. Our trial will participate in the NHLBI Central Repository for study data and specimens.
All data access will follow guidelines described in the NHLBI Limited Access Data Policy
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| ID | Term |
|---|---|
| D006333 | Heart Failure |
| D004630 | Emergencies |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
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Two-arm comparison of structured usual care vs urinary sodium guided diuresis
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Triple blinded study of guideline-based care compared with a protocolized diuretic strategy using urinary sodium
| within 30 days of hospital discharge |
| Global clinical status (GCS) | measured daily using a continuous scale of 1-100 | from the time of randomization through 14 days after randomization |
| Change in natriuretic peptides | Blood measurement | from the time of randomization through the end of protocolized IV diuretics, approximately 14 days |
| Net fluid loss | difference between fluid input and urine output in ml | from the time of randomization through the end of protocolized IV diuretics, approximately 14 days |
| Total urine output | cumulative urine output in ml | from the time of randomization through the end of protocolized IV diuretics, approximately 14 days |
| Weight Loss | cumulative weight loss in pounds | from the time of randomization through the end of protocolized IV diuretics, approximately 14 days |
| Home days | Those days not in the hospital, rehab or a skilled nursing facility from the time of randomization through day 30 | within 30 days from randomization |
| Subclinical ototoxicity | As measured by shoebox audiometry with a significant change in hearing threshold (dB) across frequencies from 250-8000 Hz | at two time points: 1) the day of randomization and 2) the next calendar day after protocolized IV diuretics are stopped |
| Cumulative natriuresis | cumulative sodium excretion estimated using the NRPE (based on spot urine creatinine and sodium) | from the time of randomization through the end of protocolized diuretics, approximately 14 days |
| Average daily natriuresis | mean daily sodium excretion estimated using the NRPE (based on spot urine creatinine and sodium) | from the time of randomization through the end of protocolized diuretics, approximately 14 days |
changes in the urinary tubular injury markers such as KIM-1 and NGAL
| from the time of randomization through the end of protocolized IV diuretics, approximately 14 days |
| Hospital Length of stay | number of days in the hospital | from the ED presentation to hospital discharge, approximately 7 days |
| 180-day all cause death | all-cause death | within 180 days of hospital discharge |
| Hypotension | Incidence of symptomatic (lightheaded, chest pain) hypotension (SBP < 80 mmHg confirmed on 2 successive measurements at least 30 minutes apart) | from the time of randomization through 7 days off protocolized IV diuretics, or discharge |
| Acute Kidney Injury Differences in Epithelial sodium channel (ENaC) levels | AKI (defined as a need for renal replacement therapy or KDIGO stage 2 or greater from a serum creatinine at randomization) | from the time of randomization through 7 days off protocolized IV diuretics, or discharge |
| Cardiorenal death or Myocardial Infarction (MI) during hospitalization | Cardiorenal death or MI as adjudicated by a clinical events committee | from the time of randomization through 7 days off protocolized IV diuretics, or discharge |
| Ototoxicity or tinnitus | Clinically significant ototoxicity or tinnitus as determined by the study team | from the time of randomization through 7 days off protocolized IV diuretics, or discharge |
| Nashville |
| Tennessee |
| 37232 |
| United States |
| D013568 |
| Pathological Conditions, Signs and Symptoms |