Clinical trial NCT04481919: Randomized Controlled Trial of urinE chemiStry Guided aCute heArt faiLure treATmEnt (ESCALATE)
Official title: A Randomized Trial of Protocolized Diuretic Therapy Compared to Standard Care in Emergency Department Patients With Acute Heart Failure
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Heart Failure
Acute Heart Failure
Keywords: Diuretic Therapy
Emergency Department
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2020-07-22
Enrollment: 474
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two-arm comparison of structured usual care vs urinary sodium guided diuresis
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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:

* End Stage Renal Disease (ESRD) requiring dialysis
* Need for immediate intubation
* Acute Coronary Syndrome - presentation consistent with myocardial ischemia AND new ST-Segment elevation/depression
* Temperature \> 100.5ºF
* End Stage Heart Failure: transplant list or ventricular assist device
* Concurrent use of ototoxic medications including intravenous aminoglycosides and cisplatin
* Systolic Blood Pressure \< 90 mmHg at time of consent
* LV outflow obstruction, severe uncorrected stenotic valvular disease or severe restrictive cardiomyopathy
* Greater than 2 doses of IV diuretic administered at the time of screening from the time of the hospital presentation leading to this admission (outside hospital time is included)
* Severe, uncorrected serum electrolyte abnormalities at the time of consent (serum potassium \<3.0 mEq/L, magnesium \<1.0 mEq/L or sodium \<125 or \>150 mEq/l)
* Lack of informed consent

Primary outcomes:
measure: Clinical Status Score
timeFrame: From the time of randomization through day 14
Secondary outcomes:
measure: Congestion
timeFrame: from the time of randomization until protocol transition to oral diuretics, approximately 14 days
measure: CV Death and AHF Readmission
timeFrame: within 30 days of hospital discharge
measure: Global clinical status (GCS)
timeFrame: from the time of randomization through day 14
measure: Change in natriuretic peptides
timeFrame: from the time of randomization until protocol transition to oral diuretics, approximately 14 days
measure: Net fluid loss
timeFrame: from the time of randomization until protocol transition to oral diuretics, approximately 14 days
measure: Total urine output
timeFrame: from the time of randomization until protocol transition to oral diuretics, approximately 14 days
measure: Weight Loss
timeFrame: from the time of randomization until protocol transition to oral diuretics, approximately 14 days
measure: Home days
timeFrame: within 30 days from randomization
measure: Shift in audiometry
timeFrame: from the time of randomization until protocol transition to oral diuretics, approximately 14 days
measure: Cumulative natriuresis
timeFrame: from the time of randomization until protocol transition to oral diuretics, approximately 14 days
measure: Average daily natriuresis
timeFrame: from the time of randomization until protocol transition to oral diuretics, approximately 14 days
Other outcomes:
measure: Dyspnea score
timeFrame: from the time of randomization until protocol transition to oral diuretics, approximately 14 days
measure: Change in Kidney injury biomarkers
timeFrame: from the time of randomization until protocol transition to oral diuretics, approximately 14 days
measure: Length of stay
timeFrame: from the time of hospital admission to discharge, approximately 7 days
measure: 180-day all cause death
timeFrame: within 180 days of hospital discharge
measure: Hypotension
timeFrame: from the time of randomization through 7 days off diuretic protocol, or discharge
measure: Acute Kidney Injury Differences in Epithelial sodium channel (ENaC) levels
timeFrame: from the time of randomization through 7 days off diuretic protocol, or discharge
measure: CV death or Myocardial Infarction (MI) during hospitalization
timeFrame: from the time of randomization through 7 days off diuretic protocol, or discharge
measure: Ototoxicity or tinnitus
timeFrame: from the time of randomization through 7 days off diuretic protocol, or discharge
Locations:
city: Nashville
country: United States
facility: VA Tennessee Valley Health Service
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Sean P. Collins, MD
role: PRINCIPAL_INVESTIGATOR
References: