RAAS Optimization for Acute CHF Patients (ROAD-HF)

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: Completed
• Conditions: Acute Decompensated Heart Failure
• Intervention / Treatment: Other: Change of treatment plan

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: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Measure Description	Time Frame
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)	Baseline, 24 hours, 48 hours, 72 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	0 hours, 24 hours, 48 hours, 72 hours
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!"	0 hours, 24 hours, 48 hours, 72 hours
Kinetic EGFR Levels	Change in kinetic EGFR from baseline to 24, 48, and 72 hours.	Baseline, 24 hours, 48 hours, 72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight Change	Change in patient's weight over 3 day period.	Baseline, 24 hours, 48 hours, 72 hours
Negative Fluid Balance	Changes in net fluid loss over 24, 48, 72 hours.	Baseline, 24 hours, 48 hours, 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.	Baseline, 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.	Baseline, 48 hours
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.	Over 72 hours
Hospitalization LOS	Length of inpatient stay	Total stay during current admission
Cost Analysis	Cost of inpatient stay during admission.	Total stay during current admission
Number of patient mortality	Death within 30 days of current inpatient stay (from first day of admission)	30 days
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)	30 days
Number of patients readmitted over one year	Readmission at UF Health within 1 year of current inpatient stay (from first day of admission)	1 year

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Bhagwan Dass, MD, University of Florida

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2019
• Primary Completion (Actual): April 12, 2021
• Study Completion (Actual): April 12, 2021

Study Registration Dates

• First Submitted: September 19, 2018
• First Submitted That Met QC Criteria: October 2, 2018
• First Posted (Actual): October 3, 2018

Study Record Updates

• Last Update Posted (Actual): April 22, 2021
• Last Update Submitted That Met QC Criteria: April 21, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: ACEI (Angiotensin-Converting-Enzyme Inhibitor); ARB (Angiotensin II Receptor Blocker); CHF (Congestive Heart Failure); RAAS (Renin Angiotensin Aldosterone System)
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID 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