Diuretics vs. Afterload Reduction for Treatment of HeartLogic Alerts

Phase 4

Recruiting

• Conditions: Heart Failure, Congestive
• Interventions: Drug: sacubitril/valsartan; Drug: Furosemide; Drug: Hydralazine; Drug: Torsemide; Drug: Bumetanide; Drug: Isosorbide Dinitrate

• Registration Number: NCT06218199
• Lead Sponsor: Heart Center Research, LLC

Brief Summary

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.

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 Timeline

• Study Start: 2021-07-08
• Status Verified: 2024-01
• Study First Submitted: 2024-01-11
• Study First Submitted QC: 2024-01-11
• Study First Posted: 2024-01-23
• Last Update Submitted: 2024-01-25
• Last Update Posted: 2024-01-29
• Primary Completion: 2025-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Afterload reduction protocol	Hydralazine	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.
Diuretic protocol	Torsemide	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.
Afterload reduction protocol	sacubitril/valsartan	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.
Diuretic protocol	Furosemide	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.
Diuretic protocol	Bumetanide	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.
Afterload reduction protocol	Isosorbide Dinitrate	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.

Primary Outcome Measures

Name	Time	Method
Number of participants with recovery from HeartLogic Alert	by 30, 60, 90 days	change in HeartLogic score to ≤ 6

Secondary Outcome Measures

Name	Time	Method
Number of participants with development of symptoms of heart failure decompensation	30, 60, 90 days	change from baseline or new development of, dyspnea, orthopnea, paroxysmal nocturnal dyspnea or edema
Number of participants with unintended office visit, emergency department visit, CHF admission	30, 60, 90 days	office visit, emergency department visit and/or CHF admission
Number of participants with Heart Failure Events (HFE)	30, 60, 90 days	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.

Trial Locations

Locations (1)

Heart Center Research, LLC; 🇺🇸 Huntsville, Alabama, United States