A Prospective, Single-center, Open-label, Pilot Study to Compare the Effectiveness and Safety of Diuretics Add-On Strategy in Chronic Heart Failure Patients (DIOS 1)

Study Overview
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Brief Summary
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To compare the effectiveness and safety of diuretics add-on strategy in chronic heart failure patients

Conditions
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Congestive Heart Failure

Intervention / Treatment
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* Drug: furosemide/no spironolactone
* Drug: metolazone/no spironolactone
* Drug: furosemid/spironolactone
* Drug: metolazone/spironolactone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: dyspnea at rest or minimal activity tachypnea (respiratory rate > 20/min) or rales or pulmonary edema on chest X-ray who need diuretics add over 40mg of daily furosemide dose Exclusion Criteria: Hospitalization for acute heart failure decompensation cardiogenic shock (Systolic Blood Pressure < 80mmHg) Need or plan for renal replacement therapy (dialysis, kidney transplant) serum creatine level > 2.5mg/dl serum potassium (K+) > 5.5mg/dl daily spironolactone dose > 50mg previous thiazide or metolazone user Age > 75 years old or poor compliance patients 9. allergy, adverse drug reaction, hypersensitivity to any kinds of diuretics 10. life expectancy < 6 months (e.g. metastatic malignancy, liver cirrhosis) 11. pregnancy or women at age of childbearing potential

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1) Add furosemide/no spironolactone<br> | Drug: furosemide/no spironolactone<br>* furosemide (doubling previous furosemide dose)<br>|
| Active Comparator: 2) Add metolazone/no spironolactone<br> | Drug: metolazone/no spironolactone<br>* metolazone (add 2.5mg qod)<br>|
| Active Comparator: 3) Add furosemide/spironolactone<br> | Drug: furosemid/spironolactone<br>* furosemide (doubling previous furosemide dose)+spironolactone (doubling previous spironolactone dose or add 12.5mg BID if previous non-user)<br>|
| Active Comparator: 4) Add metolazone/spironolactone<br> | Drug: metolazone/spironolactone<br>* metolazone (add 2.5mg qod)+ spironolactone (doubling previous spironolactone dose or add 12.5mg BID if previous non-user)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| efficacy and safety of diuretics add-on strategy | 1) body weight change, symptoms & signs change, systemic impedance change 2) serum & urine creatinine change, serum & urine electrolyte change, biomarkers change, clinical outcomes ( all-cause mortality, all-cause rehospitalization, start of renal replacement therapy) | D+0, D+7, D+30, D+90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart failure, diuretics, kidney, glomerular filtration rate