Combination Diuretic Therapy for Acute Decompensated Heart Failure

Acute Decompensated Heart Failure Clinical Trial

— COMBIND-HF  

Official title:

Efficacy and Tolerability of Combination Intravenous Diuretic Therapy Versus Intravenous Loop Diuretic Therapy Alone for the Treatment of Acute Decompensated Heart Failure

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05840536
• Other study ID #: OchsnerHS
• Status: Withdrawn
• Phase: Phase 4
• Start date: May 2014
• Est. completion date: October 2015

Study information

• Verified date: April 2023
• Source: Ochsner Health System
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients with heart failure are often admitted to the hospital because they have accumulated excessive amounts of fluid, they become short of breath and congested with fluid. Removing the excess fluid is necessary to improve the patients symptoms and reduce the risk of being re-admitted to the hospital. Diuretics ("water pills") are often given through an IV to accelerate the fluid removal. Furosemide is commonly used for fluid removal, however some patients do not respond well to the medication. There are other diuretics available that can work in conjunction with furosemide and increase the rate of fluid removal. The other "water pills" have slightly different mechanisms of action in the body compared to furosemide and when combined they may increase fluid removal. The investigators hypothesize that adding chlorothiazide to furosemide will result in quicker and more effective fluid removal in heart failure patients.

Description:

The investigators will randomly assign patients to receive either furosemide alone or furosemide in combination with chlorothiazide when they are admitted to the hospital with acute heart failure and excessive volume. All patients will be monitored for rate of fluid removal, improvement in symptoms, and side-effects of the medications.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• Diagnosis of Acute Decompensated Heart Failure - by at least 1 symptom (dyspnea, exercise intolerance, weight gain, edema) and at least 1 sign (chest x-ray (CXR), elevated brain natriuretic peptide (BNP), rales, elevated jugular venous pressure (JVP)).
• History of Congestion Heart Failure (CHF) with chronic loop diuretic use for at least the past 4 weeks
• Echocardiogram in the past 12 months (to document Ejection fraction (EF))

Exclusion Criteria:

• Chronic Kidney Disease (CKD) or Acute Kidney Injury (AKI) - Cr >2.5 mg/dL
• Ventricular assist device
• Cardiogenic shock
• Need for mechanical or vasopressor support on admission
• Significant co-morbidities: Chronic Obstructive Pulmonary Disease, pneumonia, pulmonary embolism
• History of pulmonary hypertension (PAH) (World Health Organization (WHO) group I primary PAH)
• Acute Ischemia / post-intervention (Coronary Artery Bypass Graft, Percutaneous Coronary Interventions) in the past 90 days

Related Conditions & MeSH terms

• Acute Decompensated Heart Failure
• Heart Failure

Intervention

Drug:
• Furosemide plus Chlorothiazide
Patients will receive lasix infusion starting at 5mg/hr along with a bolus dose of chlorothiazide 250mg at the initiation of the protocol. The lasix infusion can be titrated to 10mg after 12hrs based on volume of diuresis. This arm will also receive 250mg bolus doses of chlorothiazide every 12hrs for the duration of the study. Intravenous (IV) lasix infusion at 5mg/hr plus IV boluses of diuril every 12 hrs.
• Furosemide
Patients will receive furosemide infusion at 5mg/hr along with an initial bolus dose of furosemide equal to twice their home oral dose. The furosemide infusion can be increased to 10mg/hr after 12hrs based on urine output. This arm will receive bolus doses of furosemide every 12hrs equal to twice their home oral dose until completion of the protocol.

Locations

Country	Name	City	State
United States	Ochsner Heart and Vascular Institute	New Orleans	Louisiana

Sponsors (1)

Lead Sponsor	Collaborator
Ochsner Health System

Country where clinical trial is conducted

United States, 

References & Publications (3)

Channer KS, McLean KA, Lawson-Matthew P, Richardson M. Combination diuretic treatment in severe heart failure: a randomised controlled trial. Br Heart J. 1994 Feb;71(2):146-50. doi: 10.1136/hrt.71.2.146. — View Citation

Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, LeWinter MM, Deswal A, Rouleau JL, Ofili EO, Anstrom KJ, Hernandez AF, McNulty SE, Velazquez EJ, Kfoury AG, Chen HH, Givertz MM, Semigran MJ, Bart BA, Mascette AM, Braunwald E, O'Connor CM; NHLBI Heart Failure Clinical Research Network. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011 Mar 3;364(9):797-805. doi: 10.1056/NEJMoa1005419. — View Citation

Peacock WF, Costanzo MR, De Marco T, Lopatin M, Wynne J, Mills RM, Emerman CL; ADHERE Scientific Advisory Committee and Investigators. Impact of intravenous loop diuretics on outcomes of patients hospitalized with acute decompensated heart failure: insights from the ADHERE registry. Cardiology. 2009;113(1):12-9. doi: 10.1159/000164149. Epub 2008 Oct 17. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Volume of Diuresis	Total volume of urine output will be collected during the first 72 hours of admission.	During Index Hospitalization at 72 hours
Primary	Change in Serum Creatinine from Baseline	Change in serum creatinine from baseline after 72 hours of diuresis	During Index Admission up to 120 hours
Secondary	Hypokalemia		From date of index hospitalization until 72 hours after diuresis
Secondary	Electrolyte Disturbances	Magnesium, Phosphorous	From date of index hospitalization until 72 hours after diuresis
Secondary	Total Weight Loss		From date of index hospitalization until 72 hours after diuresis
Secondary	Relief of Symptoms	Using the five-point Likert scale for dyspnea which ranges from 1-5 where the lower the score the better the outcome	From date of index hospitalization until 72 hours after diuresis
Secondary	Length of Stay		From date of index hospitalization until date of discharge from hospital, assessed up to 1 week
Secondary	Potassium Replacement Requirements		From date of index hospitalization until date of discharge from hospital, assessed up to 1 week
Secondary	Adverse Events	Hypotension, dizziness, syncope, acute renal failure, arrhythmia	From date of index hospitalization until date of discharge from hospital, assessed up to 1 week