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RAAS Optimization for Acute CHF Patients (ROAD-HF)

Primary Purpose

Acute Decompensated Heart Failure

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Change of treatment plan
Sponsored by
University of Florida
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Decompensated Heart Failure focused on measuring ACEI (Angiotensin-Converting-Enzyme Inhibitor), ARB (Angiotensin II Receptor Blocker), CHF (Congestive Heart Failure), RAAS (Renin Angiotensin Aldosterone System)

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UF Health at the University of Florida

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Active Comparator

Arm Label

Full Dose ACEI/ARB or Home Dose Group

No ACEI/ARB Group

Arm Description

This group will receive the full dose of ACEI/ARBs.

This group will not receive the full dose of ACEI/ARBs for the first 72 hours of hospitalization.

Outcomes

Primary Outcome Measures

Serum Creatinine Levels
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)
Patient Global Assessment (well-being) over 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
Dyspnea (shortness of breath) clinical change over 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!"
Kinetic EGFR Levels
Change in kinetic EGFR from baseline to 24, 48, and 72 hours.

Secondary Outcome Measures

Weight Change
Change in patient's weight over 3 day period.
Negative Fluid Balance
Changes in net fluid loss over 24, 48, 72 hours.
CHF Clinical Change
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.
Change in Renal Function
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.
Number of patients experiencing CHF Treatment Failure
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.
Hospitalization LOS
Length of inpatient stay
Cost Analysis
Cost of inpatient stay during admission.
Number of patient mortality
Death within 30 days of current inpatient stay (from first day of admission)
Number of patients readmitted or experiencing a ED visit
Readmission or ED visit at UF Health within 30 days of current inpatient stay (from first day of admission)
Number of patients readmitted over one year
Readmission at UF Health within 1 year of current inpatient stay (from first day of admission)

Full Information

First Posted
September 19, 2018
Last Updated
April 21, 2021
Sponsor
University of Florida
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1. Study Identification

Unique Protocol Identification Number
NCT03695120
Brief Title
RAAS Optimization for Acute CHF Patients
Acronym
ROAD-HF
Official Title
Renin Angiotensin Aldosterone Optimization in Acute Decompensated Heart Failure
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
February 8, 2019 (Actual)
Primary Completion Date
April 12, 2021 (Actual)
Study Completion Date
April 12, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Florida

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Decompensated Heart Failure
Keywords
ACEI (Angiotensin-Converting-Enzyme Inhibitor), ARB (Angiotensin II Receptor Blocker), CHF (Congestive Heart Failure), RAAS (Renin Angiotensin Aldosterone System)

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
The subjects will be randomized into a control group or variable group with an approximate 50/50 randomization. The control group will consist of subjects receiving ACEIs/ARBs. The variable group will consist of subjects that will not receive ACEI/ARBs during the first 72 hours of admission.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Full Dose ACEI/ARB or Home Dose Group
Arm Type
No Intervention
Arm Description
This group will receive the full dose of ACEI/ARBs.
Arm Title
No ACEI/ARB Group
Arm Type
Active Comparator
Arm Description
This group will not receive the full dose of ACEI/ARBs for the first 72 hours of hospitalization.
Intervention Type
Other
Intervention Name(s)
Change of treatment plan
Intervention Description
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.
Primary Outcome Measure Information:
Title
Serum Creatinine Levels
Description
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)
Time Frame
Baseline, 24 hours, 48 hours, 72 hours
Title
Patient Global Assessment (well-being) over 72 hours
Description
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
Time Frame
0 hours, 24 hours, 48 hours, 72 hours
Title
Dyspnea (shortness of breath) clinical change over 72 hours
Description
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!"
Time Frame
0 hours, 24 hours, 48 hours, 72 hours
Title
Kinetic EGFR Levels
Description
Change in kinetic EGFR from baseline to 24, 48, and 72 hours.
Time Frame
Baseline, 24 hours, 48 hours, 72 hours
Secondary Outcome Measure Information:
Title
Weight Change
Description
Change in patient's weight over 3 day period.
Time Frame
Baseline, 24 hours, 48 hours, 72 hours
Title
Negative Fluid Balance
Description
Changes in net fluid loss over 24, 48, 72 hours.
Time Frame
Baseline, 24 hours, 48 hours, 72 hours
Title
CHF Clinical Change
Description
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.
Time Frame
Baseline, 72 hours
Title
Change in Renal Function
Description
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.
Time Frame
Baseline, 48 hours
Title
Number of patients experiencing CHF Treatment Failure
Description
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.
Time Frame
Over 72 hours
Title
Hospitalization LOS
Description
Length of inpatient stay
Time Frame
Total stay during current admission
Title
Cost Analysis
Description
Cost of inpatient stay during admission.
Time Frame
Total stay during current admission
Title
Number of patient mortality
Description
Death within 30 days of current inpatient stay (from first day of admission)
Time Frame
30 days
Title
Number of patients readmitted or experiencing a ED visit
Description
Readmission or ED visit at UF Health within 30 days of current inpatient stay (from first day of admission)
Time Frame
30 days
Title
Number of patients readmitted over one year
Description
Readmission at UF Health within 1 year of current inpatient stay (from first day of admission)
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bhagwan Dass, MD
Organizational Affiliation
University of Florida
Official's Role
Principal Investigator
Facility Information:
Facility Name
UF Health at the University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
31797310
Citation
Dass B, Dimza M, Singhania G, Schwartz C, George J, Bhatt A, Radhakrishnan N, Bansari A, Bozorgmehri S, Mohandas R. Renin-Angiotensin-Aldosterone System Optimization for Acute Decompensated Heart Failure Patients (ROAD-HF): Rationale and Design. Am J Cardiovasc Drugs. 2020 Aug;20(4):373-380. doi: 10.1007/s40256-019-00389-7.
Results Reference
derived

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RAAS Optimization for Acute CHF Patients

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