RAAS Optimization for Acute CHF Patients (ROAD-HF)

April 21, 2021 updated by: University of Florida

Renin Angiotensin Aldosterone Optimization in Acute Decompensated Heart Failure

Holding ACEI/ARBs during initial 72 hours of admission with acute decompensated heart failure may help preserve renal function with a lesser decline in GFR. This treatment modification will also allow the option of aggressive diuresis in volume overloaded CHF patients which should result in a lesser decline of AKI, length of stay, readmission rates, and cost associated with CHF treatment.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The investigators hypothesize that worsening renal function can be mitigated by withholding ACEI/ARB during the initial phase of in-patient treatment with aggressive diuresis. This hypothesis will be tested by randomly allocating 360 admitted patients with ADHF on two treatment paths: 1) no ACEI/ARB administered for initial 72 hours of treatment during aggressive diuresis versus 2) full dose ACEI/ARB administered concurrently with aggressive diuresis in naïve patients/home dose, who are already on such therapy. The study team hopes to find that holding ACEI/ARBs during the initial 72 hours of admission with acute decompensated systolic heart failure will help preserve renal function, as demonstrated by a lesser decline in GFR. In addition, this treatment would allow the option of aggressive diuresis in volume overloaded CHF patients, resulting in a lesser decline of AKI, length of stay, readmission rates, and costs associated with CHF treatment. By understanding the complex interaction between holding ACEIs/ARBs and continued aggressive diuresis, the investigators intend to develop optimal dosing strategies for acute, decompensated CHF patients, further minimizing adverse events such as electrolyte issues and declining GFR/AKI.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Gainesville, Florida, United States, 32610
        • UF Health at the University of Florida

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Patients are eligible for enrollment if within the previous 24 hours they were treated with acute decompensated heart failure or diagnosed on the basis of the investigator's clinical diagnosis of heart failure, which needs to be supported by at least 2 the following criteria:

  • Elevated concentration of B-type natriuretic peptide (BNP) or N-terminal pro-BNP. (Elevated BNP" defined as >300 for sinus rhythm, >500 for patients will atrial fibrillation and elevated pro BNP defined as >1000 for sinus rhythm, >1600 for atrial fibrillation.)
  • Pulmonary edema on physical examination.
  • Radiologic pulmonary congestion or edema.
  • History of Chronic Heart Failure. Anticipated need for IV loop diuretics for at least 48 hours
  • Willingness to provide informed consent

Exclusion Criteria:

  • Previously diagnosed end-stage renal disease; Serum Potassium >5.5 mmol/L
  • Cardiogenic Shock within 48 hours, ST-segment elevation myocardial infarction, ongoing ischemia.
  • Need for renal replacement therapy through dialysis or ultrafiltration
  • Myocardial infarction within 30 days of screening.
  • Patients with systolic blood pressure of less than 90 mm Hg.
  • Patients requiring Intravenous Vasodilators or inotropic agents (other than Digoxin) for heart failure
  • BNP less than 250 ng/ml and/or proBNP less than 1000 mg/ml
  • Pregnant women, prisoners, and institutionalized individuals
  • Severe stenotic valvular disease
  • Complex congenital heart disease
  • Need for mechanical hemodynamic support
  • Sepsis
  • Terminal illness (other than HF) with expected survival of less than one year
  • Previous adverse reaction to the study drugs
  • Use of IV iodinated radiocontrast material in last 72 hours or planned during hospitalization
  • Enrollment or planned enrollment in another randomized clinical trial during this hospitalization
  • Inability to comply with planned study procedures
  • Primary admission diagnosis other than acute heart failure

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
No Intervention: Full Dose ACEI/ARB or Home Dose Group
This group will receive the full dose of ACEI/ARBs.
Active Comparator: No ACEI/ARB Group
This group will not receive the full dose of ACEI/ARBs for the first 72 hours of hospitalization.
Other: Change of treatment plan
Withholding ACEI/ARBs during initial 72 hours of admission with acute decompensated heart failure may help preserve renal function with a lesser decline in GFR. This treatment modification will also allow the option of aggressive diuresis in volume overloaded CHF patients which should result in a lesser decline of AKI, length of stay, readmission rates, and cost associated with CHF treatment.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Serum Creatinine Levels
Time Frame: Baseline, 24 hours, 48 hours, 72 hours
Change in serum creatinine from randomization. (AKI is defined as an increase in the serum creatinine level of more than 0.3 mg per deciliter over 48 hours)
Baseline, 24 hours, 48 hours, 72 hours
Patient Global Assessment (well-being) over 72 hours
Time Frame: 0 hours, 24 hours, 48 hours, 72 hours

Patient global assessments by modified scale (based on Borg and VAS) for 0, 24, 48, 72 hours. Scaled 1 - 10. A "1" means the patient feels the best they've ever felt and a "10" means the participant feels the worst they have ever felt. Following all time points collected, the area under the curve for global assessment over the first 72 hours will be a primary efficacy endpoint (AUC for PGA).

For patient well-being (PGA)

1 Best I've ever felt 2 3 Feeling good 4 5 Feeling okay 6 7 Feeling bad 8 9 Feeling terrible 10 Worst I've ever felt
0 hours, 24 hours, 48 hours, 72 hours
Dyspnea (shortness of breath) clinical change over 72 hours
Time Frame: 0 hours, 24 hours, 48 hours, 72 hours

Patient dyspnea assessments by modified scale (based on Borg and VAS) for 0, 24, 48, 72 hours. Scaled 1 - 10. A "1" means no shortness of breath and a "10" means the patient can't breathe at all. Following all time points collected, the area under the curve for dyspnea assessment over the first 72 hours will be a primary efficacy endpoint (AUC for dyspnea).

For shortness of breath (SOB)

1 No SOB at all 2 3 Slight SOB 4 5 Moderate SOB 6 7 Severe SOB 8 9 Extreme SOB 10 "I can't breathe!"
0 hours, 24 hours, 48 hours, 72 hours
Kinetic EGFR Levels
Time Frame: Baseline, 24 hours, 48 hours, 72 hours
Change in kinetic EGFR from baseline to 24, 48, and 72 hours.
Baseline, 24 hours, 48 hours, 72 hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Weight Change
Time Frame: Baseline, 24 hours, 48 hours, 72 hours
Change in patient's weight over 3 day period.
Baseline, 24 hours, 48 hours, 72 hours
Negative Fluid Balance
Time Frame: Baseline, 24 hours, 48 hours, 72 hours
Changes in net fluid loss over 24, 48, 72 hours.
Baseline, 24 hours, 48 hours, 72 hours
CHF Clinical Change
Time Frame: Baseline, 72 hours
Change in signs and symptoms of congestion (defined as jugular venous pressure of <8 cm, with no orthopnea and with trace peripheral edema or no edema) from baseline to 24, 48, 72 hours.
Baseline, 72 hours
Change in Renal Function
Time Frame: Baseline, 48 hours
Renal biomarker (NephroCheck) levels at baseline and 48 hours. All patients receive baseline NephroCheck, and 48 hour re-assessment is limited to the first 100 patients.
Baseline, 48 hours
Number of patients experiencing CHF Treatment Failure
Time Frame: Over 72 hours

Persistent or worsening heart failure requiring additional interventions. Patients requiring other intravenous vasoactive medications for heart failure (inotropes, vasodilators, etc) for clinical reasons during the randomization period will meet the secondary endpoints of "worsening or persistent heart failure" and "treatment failure."

Patients deemed to have a clinical need for additional diuretics during the study period will be permitted to receive diuretics. This will be captured as "rescue therapy" and will meet criteria for secondary endpoints of "worsening or persistent heart failure" and "treatment failure" endpoints.

Conversely, patients may develop signs or symptoms of over-diuresis (such as hypotension) that will necessitate holding or discontinuing diuretics before completion of the randomization period. This will be captured as a "treatment failure" if it requires specific intervention beyond simply holding diuretics.
Over 72 hours
Hospitalization LOS
Time Frame: Total stay during current admission
Length of inpatient stay
Total stay during current admission
Cost Analysis
Time Frame: Total stay during current admission
Cost of inpatient stay during admission.
Total stay during current admission
Number of patient mortality
Time Frame: 30 days
Death within 30 days of current inpatient stay (from first day of admission)
30 days
Number of patients readmitted or experiencing a ED visit
Time Frame: 30 days
Readmission or ED visit at UF Health within 30 days of current inpatient stay (from first day of admission)
30 days
Number of patients readmitted over one year
Time Frame: 1 year
Readmission at UF Health within 1 year of current inpatient stay (from first day of admission)
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Florida

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Bhagwan Dass, MD, University of Florida

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 8, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 12, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 12, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 19, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 2, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 3, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 22, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 21, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB201702923

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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