High-dose Aldosterone Antagonist for Acute Decompensated Heart Failure

Primary Aims

1. Evaluate the safety of high-dose spironolactone in combination of patiromer in acute decompensated heart failure patients.
2. Evaluate the efficacy of high-dose spironolactone in combination of patiromer in causing volume loss and symptom relief in patients with ADHF treated with high-dose spironolactone.

Secondary Aims

1: Evaluate the effect of high-dose spironolactone on urinary sodium excretion and renal function.

Study Overview

• Status: Completed
• Conditions: Acute Decompensated Heart Failure
• Intervention / Treatment: Drug: Spironolactone and patiromer

Detailed Description

Step-by-Step Methods:

Pre-screening: Patients meeting the inclusion and exclusion criteria will be approached to participate in the study. Informed consent will be taken at this time. These patients will receive intravenous loop diuretic per the discretion of treating physician and will be closely followed for weight loss and symptoms relief.

Screening: The patients who don't respond as measured by symptoms relief or <0.5 kg weight loss/day

1. Despite furosemide ≥ 160 mg IV total daily dose or equivalent dose of torsemide or bumetanide. (1 mg bumetanide = 10 mg torsemide = 20 mg furosemide). OR
2. After 48 hours irrespective of diuretic dose.

will be considered for the study intervention. Patients who have not participated in the pre-screening phase and do not respond adequately to furosemide >160 mg iv daily dose will directly be enrolled into active intervention part of the study.

Intervention (High-Dose Spironolactone + Patiromer): Patients will be initiated on spironolactone 100 mg orally once daily along with patiromer 8.4 gm orally (if serum K >4.3 meq/L). The dose of loop diuretic will stay same during rest of the study period. On day 2, the dose of spironolactone will be titrated to 200 mg orally once a day depending on the diuretic response and lab results. Serum potassium will be monitored twice a day. The dose of patiromer will be increased to 16.8 gm in patients with potassium levels exceeding 5.5 meq/L; or it will be held for serum K <4.3 mEq/L. Treatment will continue till patients achieve euvolemia or get discharged. Euvolemia is defined as resolution of symptoms and signs of volume overload.

Patients will be followed till achievement of euvolemia or discharge. Daily assessment will be done for symptoms, and signs of volume overload including shortness of breath, orthopnea, paroxysmal nocturnal dyspnea, abdominal bloating, lower extremity edema, JVD, and body weight changes. Serum chemistry will be assessed twice a day and urine electrolytes once a day. Neurohormonal analysis will be done at the pre-screening, initiation of active intervention and at the end of the study duration.

Primary Safety Endpoints:

1. Incidence of hyperkalemia as defined by serum K >5.5 meq/day.
2. Renal function: assessed by daily serum creatinine

Primary Efficacy Endpoints:

1. Weight loss: using same calibrated scale every day in hospital gown.
2. Symptom relief: assessed using a 5-point Likert scale describing magnitude of shortness of breath while the patient is in the supine position.

• Study Type: Observational
• Enrollment (Actual): 48

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • Shweta Bansal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects will have been hospitalized with a diagnosis of chronic heart failure.

Description

Inclusion Criteria:

1. More than18 years old
2. Hospitalized with history of chronic heart failure and at least one symptom (dyspnea, orthopnea or edema) and one sign (rales, peripheral edema, ascites, or radiographic pulmonary edema or pleural effusion)
3. Use of loop diuretics
4. Women of child bearing age with negative urine pregnancy test

Exclusion Criteria:

1. Acute coronary syndrome
2. Patients with a baseline eGFR < 30 ml/min by MDRD equation
3. Baseline potassium concentration ≥ 5.5 mEq/L
4. Requirement for intravenous vasodilators or inotropic agents
5. Systemic infection
6. Patients with concomitant end-stage liver disease
7. Hemodynamically significant uncorrected valvular disease
8. Patients with pulmonary embolism
9. Patients with high output heart failure
10. Pregnant patients

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Intervention; Spironolactone and patiromer	Drug: Spironolactone and patiromer; High dose spironolactone with or without patiromer based on the patient's baseline potassium; Other Names: Aldactone and veltassa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight loss	Improved swelling and shortness of breath suggestive of volume loss	up to 10 days
symptoms relief	Improved swelling and shortness of breath suggestive of volume loss	up to 10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypo- or hyperkalemia	Serum potassium <3.5 or >5.5 meq/l	up to 10 days
Urinary FENa and Urinary Na/K ratio	to measure the sodium loss	Up to 10 days

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Collaborators: Relypsa, Inc.
• Investigators: Principal Investigator: Shweta Bansal, UT Health San Antonio

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: June 27, 2016
• First Submitted That Met QC Criteria: June 30, 2016
• First Posted (Estimate): July 6, 2016

Study Record Updates

• Last Update Posted (Actual): May 3, 2019
• Last Update Submitted That Met QC Criteria: April 30, 2019
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Spironolactone
• Other Study ID Numbers: HSC20160252H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided