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

NCT ID: NCT04481919

Last Updated: 2025-12-19

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 474 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-01
• Study Completion Date: 2026-12-31

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.

Conditions

Heart Failure; Acute Heart Failure

Keywords

Diuretic Therapy; Emergency Department

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Protocolized spot urine sodium guided 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.

Group Type: ACTIVE_COMPARATOR

Protocolized diuretic therapy

Intervention Type: 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.

Guideline-based care

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Sean Collins

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sean P. Collins, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

VA Tennessee Valley Health Service

Nashville, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 37544492 (View on PubMed)

Other Identifiers

190690

Identifier Type: -

Identifier Source: org_study_id