Diuretics vs Afterload Reduction for Congestive Heart Failure
(DART-HA Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Heart Center Research, LLC
Must not be taking: Inotropes, Diuretics
Disqualifiers: Renal failure, Heart transplant, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should not have standard contraindications to certain heart failure medications, which might imply some restrictions. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug torasemide for treating congestive heart failure?
Research shows that torasemide, a loop diuretic, is effective in treating congestive heart failure by reducing symptoms like fluid retention and improving heart function. It has a longer duration of action and better absorption compared to furosemide, making it a reliable option for managing heart failure symptoms.
12345What makes the drug combination in the trial unique for treating congestive heart failure?
This drug combination is unique because it includes both diuretics like Bumetanide, Furosemide, and Torsemide, which help remove excess fluid from the body, and afterload reducers like Hydralazine and Isosorbide Dinitrate, which help relax blood vessels and reduce the heart's workload. This dual approach targets both fluid overload and high blood pressure, which are common issues in congestive heart failure.
678910Eligibility Criteria
This trial is for people with a Boston Scientific device monitoring heart failure who don't have new symptoms but show diagnostic feature abnormalities. They can't have severe kidney issues, ongoing heart failure symptoms, recent arrhythmia changes, or be pregnant. Stable blood pressure and no history of certain drug reactions are required.Inclusion Criteria
I don't have conditions that would make taking Sacubitril/valsartan unsafe for me.
Boston Scientific device with HeartLogic enabled
Exclusion Criteria
The subject is implanted with unipolar RA or RV leads
My kidney function is very low, and water pills don't work for me or I'm on dialysis.
I have severe heart failure symptoms even when resting.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Remote Monitoring
Subjects with CHF are remotely monitored for HeartLogic score elevations
Ongoing
Treatment
Participants are randomized to observation, diuretic, or afterload reduction therapy based on HeartLogic alerts
Up to 90 days
Recheck HeartLogic index 7 days after initiation of treatment
Follow-up
Participants are monitored for safety and effectiveness after treatment
90 days
Visits at 30, 60, and 90 days
Participant Groups
The DART-HA study compares standard treatments for congestive heart failure: observation alone versus diuretics (like Furosemide) or afterload reducers (like sacubitril/valsartan). It's to see which treatment works best when HeartLogic alerts occur without new symptoms.
3Treatment groups
Active Control
Group I: Observation protocolActive Control1 Intervention
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.
Group II: Diuretic protocolActive Control3 Interventions
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.
Group III: Afterload reduction protocolActive Control3 Interventions
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.
Bumetanide is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Bumetanide for:
- Edema secondary to cardiac failure
- Edema secondary to hepatic disease
- Edema secondary to renal disease
- Nephrotic syndrome
- Hypertension
🇪🇺 Approved in European Union as Bumetanide for:
- Oedema associated with congestive heart failure
- Oedema associated with hepatic cirrhosis
- Oedema associated with a nephrotic syndrome
- Hypertension
🇨🇦 Approved in Canada as Bumetanide for:
- Edema secondary to congestive heart failure
- Edema secondary to hepatic cirrhosis
- Edema secondary to nephrotic syndrome
- Hypertension
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Heart Center Research, LLCHuntsville, AL
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Who Is Running the Clinical Trial?
Heart Center Research, LLCLead Sponsor
Boston Scientific CorporationIndustry Sponsor
References
Efficacy of oral torasemide in dogs with degenerative mitral valve disease and new onset congestive heart failure: The CARPODIEM study. [2021]Torasemide is a potent loop diuretic with potential to treat congestive heart failure (CHF) in dogs.
Effect of torsemide and furosemide on clinical, laboratory, radiographic and quality of life variables in dogs with heart failure secondary to mitral valve disease. [2018]Diuretic therapy reduces preload and relieves congestion secondary to cardiac dysfunction. Torsemide (torasemide) is a loop diuretic with longer duration of action, decreased susceptibility to diuretic resistance, and adjunctive aldosterone antagonist properties compared with furosemide. We hypothesized that torsemide would be well tolerated and no less effective than furosemide at diuresis, control of clinical signs, and maintenance of quality of life (QOL) in dogs with congestive heart failure (CHF).
Acute and long term effects of loop diuretics in heart failure. [2018]Diuretics, together with digitalis glycosides and vasodilators are of prime importance in the medical treatment of patients with congestive heart failure (CHF). Diuretics provide quick symptomatic relief in these patients. Their beneficial effect is related to the promotion of sodium and water excretion via the kidney, thus reducing extracellular fluid volume expansion and mitigating the increase in preload and afterload caused by sodium and water retention. Loop diuretics administered intravenously are indispensable in the management of pulmonary oedema; thiazides and loop diuretics in low doses are effectively used in the oral treatment of mild to moderate heart failure. Torasemide is a new loop diuretic which differs from furosemide (frusemide) and related loop diuretics by virtue of its longer elimination half-life and longer duration of action, with almost complete bioavailability. The efficacy and tolerability of torasemide have been compared with furosemide in several studies. Once daily oral administration of torasemide (starting with 5mg) or furosemide 40mg reduce bodyweight, oedema and symptoms of heart failure to a similar extent. Mean New York Heart Association class is consistently reduced by 0.5 to 0.7. Intravenous administration attenuates the increase in intracardiac pressures during exercise in patients with CHF, and produces acute improvements in cardiac haemodynamics in patients with high grade left heart failure. A beneficial effect on both pulmonary and cardiac haemodynamics has been demonstrated during chronic oral treatment of patients with previously untreated CHF. Torasemide was well tolerated with only mild and transient adverse effects reported in a small number of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
[Torasemide is the effective loop diuretic for long-term therapy of arterial hypertension]. [2018]Torasemide is a loop diuretic and has been used for the treatment of both acute and chronic congestive heart failure (CHF) and arterial hypertension (AH). Torasemide is similar to other loop diuretics in terms of its mechanism of diuretic action. It has higher bioavailability (>80%) and a longer elimination half-life (3 to 4 hours) than furosemide. In the treatment of CHF torasemide (5 to 20 mg/day) has been shown to be an effective diuretic. Non-diuretic dosages (2.5 to 5 mg/day) of torasemide have been used to treat essential AH, both as monotherapy and in combination with other antihypertensive agents. When used in these dosages, torasemide lowers diastolic blood pressure to below 90mm Hg in 70 to 80% of patients. Antihypertensive efficacy of torasemide is similar to that of thiazides and related compounds. Thus low-dose torasemide constitutes an alternative to thiazides in the treatment of essential AH.
Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure. [2019]Because the bioavailability of oral furosemide is erratic and often incomplete, we tested the hypothesis that patients with heart failure who were treated with torsemide, a predictably absorbed diuretic, would have more favorable clinical outcomes than would those treated with furosemide.
Partially reversible bortezomib-induced cardiotoxicity: an unusual cause of acute cardiomyopathy. [2020]Chemotherapy-associated cardiotoxicity can present as a spectrum from arrhythmia to acute congestive heart failure. Unlike anthracyclines, proteasome inhibitors - for example, bortezomib - are not notorious for causing cardiotoxicity in absence of pre-existing cardiac dysfunction or without concomitant use of other cardiotoxic agents. We describe a 66-year-old woman with end-stage renal disease who developed acute dyspnea hours after a third treatment with bortezomib for IgG kappa myeloma. The Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 5) between bortezomib and acute left ventricular dysfunction. Patients receiving proteasome inhibitors should be closely monitored for evidence of cardiac dysfunction during treatment.
Multiple myeloma presenting with high-output heart failure and improving with anti-angiogenesis therapy: two case reports and a review of the literature. [2021]Common manifestations of multiple myeloma include osteolytic lesions, cytopenias, hypercalcemia, and renal insufficiency. Patients may also exhibit heart failure which is often associated with either past therapy or cardiac amyloidosis. A less recognized mechanism is high-output heart failure. Diuretic therapy in this setting has little efficacy in treating the congested state. Furthermore, effective pharmacotherapy has not been established. We report two patients with multiple myeloma and high-output heart failure who failed diuretic therapy. The patients were given dexamethasone in conjunction with lenalidomide and thalidomide, respectively. Shortly thereafter, each patient demonstrated a significant improvement in symptoms. This is the first report of successful treatment of multiple myeloma-induced high-output failure via the utilization of these agents.
Efficacy of pomalidomide in a multiple myeloma patient requiring hemodialysis. [2017]A 67-year-old male patient developed multiple myeloma with acute renal failure caused by myeloma kidney. Although a very good partial response was achieved with bortezomib with dexamethasone (BD) therapy under temporary dialysis, relapse occurred 3 years later. Thalidomide was added to the BD therapy but was discontinued because of drug-induced eczema. Subsequently, bone lesions and chromosomal abnormalities appeared. Because renal failure progressed with increased serum free light chain levels, maintenance hemodialysis was introduced. Administration of lenalidomide showed no effect due to intolerance. BD therapy was re-started, but diffuse ground-glass opacity with pleural effusion was observed in both lungs, leading to the discontinuation of this treatment. Subsequently, pomalidomide with low-dose dexamethasone (PD) therapy was begun under hemodialysis. Seven cycles of PD therapy maintained disease stability. However, a dosage adjustment was needed because of pancytopenia. Maintaining the therapeutic effect apparently required a pomalidomide dose of 4 mg/day in this case. These findings suggest that pomalidomide is useful in relapsed or refractory advanced myeloma, with careful dose reductions and supportive care, even for patients with renal failure requiring hemodialysis.
Acute severe cardiac failure in a myeloma patient due to proteasome inhibitor bortezomib. [2021]We present here a case of severe congestive cardiac failure, in a 47-year-old patient with myeloma who had no prior cardiac history, after receiving bortezomib. Bortezomib is a boron-containing molecule, which reversibly inhibits the proteasome, an intracellular organelle, which is central to the breakdown of ubiquitinated proteins and consequently crucial for normal cellular homeostasis. Phase II clinical trials demonstrate that it is effective for the treatment of relapsed refractory myeloma. Acute development of congestive cardiac failure associated with bortezomib therapy occurs very rarely or may be underestimated. Inhibition of proteasome activity may impair cardiac function due to accumulation of unfolded, damaged and undegraded proteins in myocytes. Patients with or without cardiac disease or previously received anthracycline-containing regimes should be closely monitored when being subjected to treatment with bortezomib.
A retrospective analysis of 3954 patients in phase 2/3 trials of bortezomib for the treatment of multiple myeloma: towards providing a benchmark for the cardiac safety profile of proteasome inhibition in multiple myeloma. [2019]This retrospective analysis aimed to establish the overall cardiac safety profile of bortezomib using patient-level data from one phase 2 and seven phase 3 studies in previously untreated and relapsed/refractory multiple myeloma (MM). Seven clinically relevant primary [congestive heart failure (CHF), arrhythmias, ischaemic heart disease (IHD), cardiac death] and secondary (hypertension, dyspnoea, oedema) cardiac endpoints were defined based on MedDRA v16.0 preferred terms. 2509 bortezomib-treated patients and 1445 patients in non-bortezomib-based control arms were included. The incidence of grade ≥3 CHF was 1·3-4·0% in studies in relapsed/refractory MM and 1·2-4·7% in previously untreated MM (2·0-7·6% all grades), with no significant differences between bortezomib- and non-bortezomib-based arms in comparative studies. Incidences of arrhythmias (1·3-5·9% grade ≥2; 0·6-4·1% grade ≥3), IHD (1·2-2·9% all grades; 0·4-2·7% grade ≥3) and cardiac death (0-1·4%) were low, with no differences between bortezomib-based and non-bortezomib-based arms. Higher rates of oedema (mostly grade 1/2) were seen in bortezomib-based versus non-bortezomib-based arms in one study and a pooled transplant study analysis. Logistic regression analyses of comparative studies showed no impact on cardiac risk with bortezomib-based versus non-bortezomib-based treatment. Bortezomib-based treatment was associated with low incidences of cardiac events.