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

Phase 2

Recruiting

• Conditions: Heart Failure; Acute Heart Failure
• Interventions: Drug: Protocolized diuretic therapy

• Registration Number: NCT04481919
• Lead Sponsor: Vanderbilt University Medical Center

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.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2020-07-19
• Study First Submitted QC: 2020-07-19
• Study First Posted: 2020-07-22
• Study Start: 2022-05-01
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-02
• Last Update Posted: 2024-10-04
• Primary Completion: 2026-09-30
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 474

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Protocolized spot urine sodium guided diuretic therapy	Protocolized diuretic therapy	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.

Primary Outcome Measures

Name	Time	Method
Clinical Status Score	From the time of randomization through day 14	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).

Secondary Outcome Measures

Name	Time	Method
CV Death and AHF Readmission	within 30 days of hospital discharge	Cardiovascular death and Acute Heart Failure Readmission
Congestion	from the time of randomization until protocol transition to oral diuretics, approximately 14 days	Daily orthodema score
Global clinical status (GCS)	from the time of randomization through day 14	measured daily using a continuous scale of 1-100
Change in natriuretic peptides	from the time of randomization until protocol transition to oral diuretics, approximately 14 days	Blood measurement
Net fluid loss	from the time of randomization until protocol transition to oral diuretics, approximately 14 days	difference between fluid input and urine output in ml
Total urine output	from the time of randomization until protocol transition to oral diuretics, approximately 14 days	cumulative urine output in ml
Weight Loss	from the time of randomization until protocol transition to oral diuretics, approximately 14 days	cumulative weight loss in pounds
Home days	within 30 days from randomization	Those days not in the hospital, rehab or a skilled nursing facility
Shift in audiometry	from the time of randomization until protocol transition to oral diuretics, approximately 14 days	Significant change in hearing threshold (dB) across frequencies from 250-8000 Hz
Cumulative natriuresis	from the time of randomization until protocol transition to oral diuretics, approximately 14 days	cumulative sodium excretion estimated using the NRPE (based on spot urine creatinine and sodium)
Average daily natriuresis	from the time of randomization until protocol transition to oral diuretics, approximately 14 days	mean daily sodium excretion estimated using the NRPE (based on spot urine creatinine and sodium)

Trial Locations

Locations (2)

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

VA Tennessee Valley Health Service; 🇺🇸 Nashville, Tennessee, United States