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

NCT04481919 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 190690
• Study Type: interventional
• Target: 474
• Locations: 1 country
• Sites: 2

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.

Conditions

Heart Failure; Acute Heart Failure

Keywords

Diuretic Therapy; Emergency Department

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Inpatient clinical congestion

  from the time of randomization through the end of protocolized IV diuretics, approximately 14 days

• Cardiorenal Death and AHF Readmission

  within 30 days of hospital discharge

• Global clinical status (GCS)

  from the time of randomization through 14 days after randomization

• Change in natriuretic peptides

  from the time of randomization through the end of protocolized IV diuretics, approximately 14 days

• Net fluid loss

  from the time of randomization through the end of protocolized IV diuretics, approximately 14 days

Other Outcomes (8)

• Dyspnea score

  from the time of randomization through the end of protocolized IV diuretics, approximately 14 days

• Change in Kidney injury biomarkers

  from the time of randomization through the end of protocolized IV diuretics, approximately 14 days

• Hospital Length of stay

  from the ED presentation to hospital discharge, approximately 7 days

Study Arms (2)

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.

Drug: Protocolized diuretic therapy

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.

Interventions

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.

Protocolized spot urine sodium guided diuretic therapy

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (2)

VA Tennessee Valley Health Service

Nashville, Tennessee, 37232, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• 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.

  PMID: 37544492 DERIVED

MeSH Terms

Conditions

Heart Failure; Emergencies

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Sean P. Collins, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Triple blinded study of guideline-based care compared with a protocolized diuretic strategy using urinary sodium
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Two-arm comparison of structured usual care vs urinary sodium guided diuresis

Study Record Dates

• First Submitted: July 19, 2020
• First Posted: July 22, 2020
• Study Start: May 1, 2022
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: December 19, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Access Criteria: 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

Locations

US (2)