Protocolized Diuretic Therapy Compared to Standard Care in Emergency Department Patients With Acute Heart Failure

Sponsor
Vanderbilt University Medical Center (Other)
Overall Status
Recruiting
CT.gov ID
NCT04481919
Collaborator
(none)
484
2
2
56
242
4.3

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Protocolized diuretic therapy
Phase 2

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: 1) result in significant improvement in global clinical status at 5 days relative to structured usual care, and 2) result in significant improvement in congestion at 5 days and in global rank at 30 days relative to structured usual care. Early protocolized treatment of patients with AHF will more rapidly improve dyspnea, avoid development of in-hospital WHF, result in greater decongestion at hospital discharge, and therefore prevent HF-related readmissions and CV death.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
484 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Two-arm comparison of structured usual care vs urinary sodium guided diuresisTwo-arm comparison of structured usual care vs urinary sodium guided diuresis
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Triple blinded study of guideline-based care compared with a protocolized diuretic strategy using urinary sodium
Primary Purpose:
Treatment
Official Title:
A Randomized Trial of Protocolized Diuretic Therapy Compared to Standard Care in Emergency Department Patients With Acute Heart Failure
Actual Study Start Date :
May 1, 2022
Anticipated Primary Completion Date :
Sep 30, 2026
Anticipated Study Completion Date :
Dec 31, 2026

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: 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.

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.

No Intervention: 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.

Outcome Measures

Primary Outcome Measures

  1. Days of clinical benefit [From randomization through day 14]

    Captures global clinical status, hospital days and death

  2. Improvement in global clinical status (GCS) [72 hours after randomization]

    Measured on the Likert scale

Secondary Outcome Measures

  1. Congestion [72 hours after randomization]

    Based on the orthodema score

  2. Death and Readmission [30 days]

    Cardiovascular death and Acute Heart Failure readmission

Other Outcome Measures

  1. Dyspnea score [5 days after randomization or hospital discharge whichever comes first]

    VAS scale

  2. Congestion [5 days after randomization or hospital discharge whichever comes first]

    Based on the orthodema score

  3. Natriuretic peptide levels [At hospital discharge and 7-day follow-up]

    Blood measurement

  4. Heart Failure readmission and Cardiovascular death [At 90 days]

  5. Readmission and all-cause death [At 30 days and at 90 days]

  6. Differences in Epithelial Sodium Channel (ENaC) levels Web results Differences in Epithelial sodium channel (ENaC) levels [Up to 90 days]

    Between those with and without Worsening Heart Failure

  7. Death and Readmission [180 days]

    CV death and acute heart failure readmission

Eligibility Criteria

Criteria

Ages Eligible for Study:
19 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Age > 18

  • Emergency Department diagnosis of Acute Heart Failure (AHF)

  • Any one of the following:

  1. 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

  • 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

  • Lack of informed consent

Contacts and Locations

Locations

Site City State Country Postal Code
1 VA Tennessee Valley Health Service Nashville Tennessee United States 37232
2 Vanderbilt University Medical Center Nashville Tennessee United States 37232

Sponsors and Collaborators

  • Vanderbilt University Medical Center

Investigators

  • Principal Investigator: Sean P. Collins, MD, Vanderbilt University Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Sean Collins, Professor, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier:
NCT04481919
Other Study ID Numbers:
  • 190690
First Posted:
Jul 22, 2020
Last Update Posted:
May 25, 2022
Last Verified:
May 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Keywords provided by Sean Collins, Professor, Vanderbilt University Medical Center
Additional relevant MeSH terms:

Study Results

No Results Posted as of May 25, 2022