Clinical trial NCT02823626: High-dose Aldosterone Antagonist for Acute Decompensated Heart Failure
Official title: High-dose Aldosterone Antagonist for Acute Decompensated Heart Failure
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Decompensated Heart Failure
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
Collaborators: name: Relypsa, Inc.
First posted: 2016-07-06
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects will have been hospitalized with a diagnosis of chronic heart failure.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Weight loss
timeFrame: up to 10 days
measure: symptoms relief
timeFrame: up to 10 days
Secondary outcomes:
measure: Hypo- or hyperkalemia
timeFrame: up to 10 days
measure: Urinary FENa and Urinary Na/K ratio
timeFrame: Up to 10 days
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Shweta Bansal
state: Texas
Study officials:
affiliation: UT Health San Antonio
name: Shweta Bansal
role: PRINCIPAL_INVESTIGATOR
References: