Combination Diuretic Therapy for Acute Decompensated Heart Failure

NCT05840536 | Withdrawn Phase 4 DMC

• 1 other identifier: OchsnerHS
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Decompensated Heart Failure

Keywords

heart failure; acute; diuretic; management; renal function; chlorothiazide; furosemide

Outcome Measures

Primary Outcomes (2)

• Volume of Diuresis

  Total volume of urine output will be collected during the first 72 hours of admission.

  During Index Hospitalization at 72 hours

• 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 Outcomes (7)

• Hypokalemia

  From date of index hospitalization until 72 hours after diuresis

• Electrolyte Disturbances

  From date of index hospitalization until 72 hours after diuresis

• Total Weight Loss

  From date of index hospitalization until 72 hours after diuresis

• Relief of Symptoms

  From date of index hospitalization until 72 hours after diuresis

• Length of Stay

  From date of index hospitalization until date of discharge from hospital, assessed up to 1 week

Study Arms (2)

Combination Diuretic Therapy

EXPERIMENTAL

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.

Drug: Furosemide plus Chlorothiazide; Drug: Furosemide

Monotherapy Diuretic

ACTIVE COMPARATOR

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.

Drug: Furosemide

Interventions

Furosemide plus Chlorothiazide DRUG

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.

Also known as: Lasix plus Diuril

Combination Diuretic Therapy

Furosemide DRUG

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.

Also known as: Lasix

Combination Diuretic Therapy; Monotherapy Diuretic

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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))

You may not qualify if:

• 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

Sponsors & Collaborators

• Ochsner Health System: lead

Study Sites (1)

Ochsner Heart and Vascular Institute

New Orleans, Louisiana, 70121, United States

Location

Related Publications (3)

• 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.

  PMID: 21366472 BACKGROUND

• 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.

  PMID: 8130022 BACKGROUND

• 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.

  PMID: 18931492 BACKGROUND

MeSH Terms

Conditions

Heart Failure

Interventions

Furosemide; Chlorothiazide

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds; Benzothiadiazines; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Patrick T Campbell, MD

  Ochsner Heart and Vascular Institute

  STUDY DIRECTOR

• Stacy Mandras, MD

  Ochsner Heart and Vascular Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2014
• First Posted: May 3, 2023
• Study Start: May 1, 2014
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: May 3, 2023

Record last verified: 2023-04

Locations

US (1)