Randomized Controlled Trial of urinE chemiStry Guided aCute heArt faiLure treATmEnt (ESCALATE)

Heart Failure Clinical Trial

— ESCALATE  

Official title:

A Randomized Trial of Protocolized Diuretic Therapy Compared to Standard Care in Emergency Department Patients With Acute Heart Failure

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04481919
• Other study ID #: 190690
• Status: Recruiting
• Phase: Phase 2
• Start date: May 1, 2022
• Est. completion date: December 31, 2026

Study information

• Verified date: September 2023
• Source: Vanderbilt University Medical Center
• Contact: Sean P. Collins, MD
• Phone: 615-936-0253
• Email: sean.collins[@]vumc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 474
• Est. completion date: December 31, 2026
• Est. primary completion date: September 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Heart Failure
• Heart Failure

Intervention

Drug:
• Protocolized diuretic therapy
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.

Locations

Country	Name	City	State
United States	VA Tennessee Valley Health Service	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Dyspnea score	measured daily using a continuous scale from 1-100	from the time of randomization until protocol transition to oral diuretics, approximately 14 days
Other	Change in Kidney injury biomarkers	changes in the urinary tubular injury markers including KIM-1 and NGAL	from the time of randomization until protocol transition to oral diuretics, approximately 14 days
Other	Length of stay	number of days in the hospital	from the time of hospital admission to discharge, approximately 7 days
Other	180-day all cause death	all-cause death	within 180 days of hospital discharge
Other	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 diuretic protocol, or discharge
Other	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 diuretic protocol, or discharge
Other	CV death or Myocardial Infarction (MI) during hospitalization	CV death or MI as adjudicated by a clinical events committee	from the time of randomization through 7 days off diuretic protocol, or discharge
Other	Ototoxicity or tinnitus	Clinically significant ototoxicity or tinnitus as determined by the study team	from the time of randomization through 7 days off diuretic protocol, or discharge
Primary	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
Secondary	Congestion	Daily orthodema score	from the time of randomization until protocol transition to oral diuretics, approximately 14 days
Secondary	CV Death and AHF Readmission	Cardiovascular death and Acute Heart Failure Readmission	within 30 days of hospital discharge
Secondary	Global clinical status (GCS)	measured daily using a continuous scale of 1-100	from the time of randomization through day 14
Secondary	Change in natriuretic peptides	Blood measurement	from the time of randomization until protocol transition to oral diuretics, approximately 14 days
Secondary	Net fluid loss	difference between fluid input and urine output in ml	from the time of randomization until protocol transition to oral diuretics, approximately 14 days
Secondary	Total urine output	cumulative urine output in ml	from the time of randomization until protocol transition to oral diuretics, approximately 14 days
Secondary	Weight Loss	cumulative weight loss in pounds	from the time of randomization until protocol transition to oral diuretics, approximately 14 days
Secondary	Home days	Those days not in the hospital, rehab or a skilled nursing facility	within 30 days from randomization
Secondary	Shift in audiometry	Significant change in hearing threshold (dB) across frequencies from 250-8000 Hz	from the time of randomization until protocol transition to oral diuretics, approximately 14 days
Secondary	Cumulative natriuresis	cumulative sodium excretion estimated using the NRPE (based on spot urine creatinine and sodium)	from the time of randomization until protocol transition to oral diuretics, approximately 14 days
Secondary	Average daily natriuresis	mean daily sodium excretion estimated using the NRPE (based on spot urine creatinine and sodium)	from the time of randomization until protocol transition to oral diuretics, approximately 14 days