Diuretics vs. Afterload Reduction for Treatment of HeartLogic Alerts (DART-HA)

Diuretics vs. Afterload Reduction for Treatment of HeartLogic Alerts (DART-HA)

The DART-HA study is a single-center, open label, trial intended to evaluate the clinical efficacy of standard treatment options for congestive heart failure (observation, diuretic or afterload reduction therapy) in patients without new symptoms who have developed abnormalities of the HeartLogic heart failure diagnostic feature.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure, Congestive
• Intervention / Treatment: Drug: Furosemide; Drug: Torsemide; Drug: Bumetanide; Drug: sacubitril/valsartan; Drug: Hydralazine; Drug: Isosorbide Dinitrate

Detailed Description

Subjects with congestive heart failure (CHF) who have undergone implantation of a Boston Scientific pacemaker/defibrillator with a HeartLogic sensor will be remotely monitored for for elevation of their HeartLogic score which is indicative of worsening heart failure. Subjects whose devices demonstrate HeartLogic score elevations and also do not demonstrate symptoms from heart failure will be randomized to observation or one of two standard treatments for worsening heart failure, afterload reduction or diuretic therapy. Subjects will be followed to assess the change in HeartLogic score, incidence of the the HeartLogic score returning to normal levels, the development of symptoms of heart failure and/or the need for treatment for heart failure.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: COO; Phone Number: 256-519-8472; Email: leskridge@theheartcenter.md

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Recruiting
      • Heart Center Research, LLC
      • Principal Investigator: Jay Dinerman, MD
      • Contact: COO; Phone Number: 256-519-8472; Email: leskridge@theheartcenter.md

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Boston Scientific device with HeartLogic enabled

• Lack of standard contraindications to Sacubitril/valsartan:

  • history of ACE-inhibitor induced angioedema and in those with angiotensin II receptor blocker (ARB) therapy induced angioedema.
  • hypotension, hypovolemia
  • renal artery stenosis, renal failure
  • hyperkalemia
  • hepatic disease Child-Pugh class C
  • Pregnancy/Breast-feeding
• Lack of standard contraindications to diuretic therapy
• Systolic Blood Pressure > 105

Exclusion Criteria:

• Glomerular filtration rate <25 mL/min who are non-responsive to diuretic therapy or are on chronic renal dialysis
• ongoing symptoms of heart failure decompensation (increased dyspnea and/or fatigue, for purposes of this study increased weight is not considered, see question 2 KCCQ).
• recent significant change in arrhythmia burden (within the past 2 weeks)
• in cardiac resynchronization therapy (CRT) patients, recent change (60 days) in effective delivery of CRT (eg. decreased biventricular paving %)
• the subject is unable to sign or refuses to sign the patient informed consent
• Symptomatic heart failure at rest or New York Heart Association Class IV at the time of enrollment
• the subject is implanted with unipolar right atrial or right ventricular leads
• subject has received or is scheduled to receive a heart transplant or ventricular assist device within the next 6 months
• subject is pregnant or planning to become pregnant during the study
• regularly scheduled IV heart failure therapy (e.g. inotropes or diuretics)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Diuretic protocol; If asymptomatic at time of HeartLogic(HL) alert, will add or increase diuretic based on current medications. If currently taking ≤ 20 mg. furosemide, begin furosemide 40mg orally daily until recovery from alert or re-alert. If currently taking ≥ 40mg furosemide begin torsemide 20 mg orally daily or bumetanide 1 mg orally daily. If patient unable to obtain torsemide or bumetanide double furosemide daily dose (maximum 480mg daily). If currently taking ≥ 20mg torsemide or ≥ 1mg bumetanide, double daily dose. Recheck HeartLogic index 7 days following initiation of diuretic protocol. If patient recovers from alert consider reducing dose or stopping diuretic. If HeartLogic index is lower but still in alert continue current diuretic dose. If HeartLogic index is the same or higher double diuretic dose and/or add metolazone 2.5mg for 1-2 days.	Drug: Furosemide; oral administration; Other Names: Lasix; Drug: Torsemide; oral administration; Other Names: Demadex; Drug: Bumetanide; oral administration; Other Names: Bumex
Active Comparator: Afterload reduction protocol; If asymptomatic at time of HL alert, increase afterload reduction drugs based on current medications. If on Sacubitril/valsartan, double the dose. If on maximum Sacubitril/valsartan, add Hydralazine 10mg and Isordil10 mg both three times a day. If on Angiotensin Receptor Blocker (ARB) at low dose (less than or equal to Valsartan 160mg daily or equivalent) then stop ARB and start sacubitril/valsartan 24-26mg twice a day. If on ARB at high dose (greater than Valsartan 160mg daily or equivalent) then immediately stop ARB and start Sacubitril/valsartan 49-51mg twice a day. If on Angiotensin-converting enzyme (ACE) inhibitor at low dose (less than or equal to 10mg daily or equivalent) then immediately stop ACE inhibitor and start Sacubitril/valsartan 24-26mg twice a day after 48hours. If on ACE inhibitor at high dose (greater than Enalapril 10mg daily or equivalent) stop ACE inhibitor and start Sacubitril/valsartan 49-51mg twice a day after 48hours. Cut diuretic in half for all.	Drug: sacubitril/valsartan; oral administration; Other Names: Entresto; Drug: Hydralazine; oral administration; Other Names: Apresoline; Drug: Isosorbide Dinitrate; oral administration; Other Names: Dilatrate, Isordil
No Intervention: Observation protocol; Standard therapy offered until development of symptoms of heart failure decompensation occurs. Patients will be monitored until out of alert and at 30, 60, and 90 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with recovery from HeartLogic Alert	change in HeartLogic score to ≤ 6	by 30, 60, 90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with development of symptoms of heart failure decompensation	change from baseline or new development of, dyspnea, orthopnea, paroxysmal nocturnal dyspnea or edema	30, 60, 90 days
Number of participants with unintended office visit, emergency department visit, CHF admission	office visit, emergency department visit and/or CHF admission	30, 60, 90 days
Number of participants with Heart Failure Events (HFE)	1) the patient was admitted or 2) the patient received 1 or more IV medications (including diuretic agents, inotropes, and vasodilators), or other parenteral therapy.	30, 60, 90 days

Collaborators and Investigators

• Sponsor: Heart Center Research, LLC
• Collaborators: Boston Scientific Corporation
• Investigators: Principal Investigator: Jay Dinerman, MD, Heart Center Research, LLC

Publications and helpful links

General Publications

• Hernandez AF, Albert NM, Allen LA, Ahmed R, Averina V, Boehmer JP, Cowie MR, Chien CV, Galvao M, Klein L, Kwan B, Lam CSP, Ruble SB, Stolen CM, Stein K; MANAGE-HF Study. Multiple cArdiac seNsors for mAnaGEment of Heart Failure (MANAGE-HF) - Phase I Evaluation of the Integration and Safety of the HeartLogic Multisensor Algorithm in Patients With Heart Failure. J Card Fail. 2022 Aug;28(8):1245-1254. doi: 10.1016/j.cardfail.2022.03.349. Epub 2022 Apr 21.

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2021
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: January 11, 2024
• First Submitted That Met QC Criteria: January 11, 2024
• First Posted (Actual): January 23, 2024

Study Record Updates

• Last Update Posted (Actual): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics, Osmotic; Diuretics; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Sodium Potassium Chloride Symporter Inhibitors; Nitric Oxide Donors; Valsartan; Furosemide; Isosorbide; Isosorbide Dinitrate; Isosorbide-5-mononitrate; Sacubitril and valsartan sodium hydrate drug combination; Hydralazine; Bumetanide; Torsemide
• Other Study ID Numbers: Dart-HA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes