Optimal Heart Failure Therapy for Heart Failure

(COPILOT-HF Trial)

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Brigham and Women's Hospital

Must be taking: ARNi, SGLT2i

Must not be taking: Pulmonary hypertension therapies

Disqualifiers: Low blood pressure, Aortic stenosis, Amyloid heart disease, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing two remote care methods to improve medication plans for heart failure patients. One method uses a virtual clinic with a step-by-step approach, and the other focuses on education and remote management. The goal is to find out which method helps doctors prescribe the best medications.

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 seems to focus on optimizing heart failure treatments, so it's possible that adjustments to your medications might be part of the study.

What data supports the effectiveness of the drug combination including Sacubitril/Valsartan, beta-blockers, MRAs, and SGLT2 inhibitors for heart failure?

Research shows that Sacubitril/Valsartan, beta-blockers, MRAs, and SGLT2 inhibitors are effective in reducing mortality and improving survival in patients with heart failure with reduced ejection fraction (HFrEF). These drugs have been shown to provide benefits beyond conventional therapies, such as ACE inhibitors or ARBs, when used together. ^{1 2 3 4 5}

Is Sacubitril/Valsartan (Entresto) safe for humans?

Sacubitril/Valsartan (Entresto) is generally considered safe for treating heart failure, but it can cause side effects like low blood pressure and swelling (angioedema). It may also lead to low sodium levels in the blood (hyponatremia) in some cases, so patients should be monitored closely. ^{6 7 8 9 10}

What makes this heart failure drug unique compared to other treatments?

This treatment combines several drug classes, including ARNI (Sacubitril/Valsartan), beta blockers, MRAs, and SGLT2 inhibitors, which together offer a comprehensive approach to heart failure by reducing mortality and improving heart function. The combination of these drugs is novel because it targets multiple pathways involved in heart failure, potentially offering greater benefits than conventional therapies that typically focus on fewer mechanisms. ^{1 3 5 11 12}

Research Team

Eligibility Criteria

This trial is for heart failure patients who have seen a Mass General Brigham provider in the last 2 years, with an EF assessment in the past 24 months, and speak English or Spanish. It's not for those with severe blood pressure issues, certain heart diseases like amyloidosis or pulmonary hypertension, very low kidney function, active chemotherapy treatment, end-of-life care recipients, transplant-related cases or those on specific heart support treatments.

Inclusion Criteria

I speak English or Spanish.

Your heart function was checked in the last 24 months.

I have been diagnosed with heart failure.

Exclusion Criteria

My kidney function is severely reduced.

You are receiving care for a terminal illness or are in hospice.

I have a severe narrowing or leakage of the aortic valve in my heart.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Education

Participants receive curated patient education and provider education, followed by an alert to providers

3 months

Remote education sessions

Remote Clinic Management

Participants begin participation in a remote, pharmacist-driven heart failure clinic for medication initiation and titration

3 months

Remote clinic visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• ARNI (ARNI)
• beta blocker (Beta Blocker)
• Education-First (Behavioral)
• MRA (MRA)
• MTD (MTD)
• SGLT2i (SGLT2 Inhibitor)

Trial Overview The COPILOT-HF trial tests two remote care strategies to optimize prescriptions of guideline-directed medical therapies (like SGLT2i inhibitors and ARNI) for heart failure patients. The study randomly assigns participants to different treatment approaches and monitors them remotely within the healthcare system.

Participant Groups

Group I: Medication & Education-First Experimental Treatment 1 Intervention

Patient will immediately begin participation in a remote, pharmacist-driven heart failure clinic that will initiate and titrate medications according to a standardized medical algorithm.

Group II: Education-First Active Control 2 Interventions

Patient will first receive curated patient education, an alert to providers, and provider education, and then after 3 months begin participation in the remote heart failure clinic.

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Dr. William Curry

Brigham and Women's Hospital

Chief Medical Officer

MD from Columbia University College of Physicians and Surgeons

Dr. Scott Schissel

Brigham and Women's Hospital

Chief Executive Officer since 2021

MD from Columbia University College of Physicians and Surgeons

Boehringer Ingelheim

Industry Sponsor

Trials

2,566

Recruited

16,150,000+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Findings from Research

Mineralocorticoid receptor antagonists (MRA) have been shown to reduce heart failure hospitalizations in patients with preserved ejection fraction, with moderate-quality evidence indicating a risk ratio of 0.82, suggesting a beneficial effect.

Beta-blockers, angiotensin converting enzyme inhibitors (ACEI), and angiotensin receptor blockers (ARB) showed little to no effect on mortality or quality of life in heart failure with preserved ejection fraction, highlighting the uncertainty of their efficacy in this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beta-blockers and inhibitors of the renin-angiotensin aldosterone system for chronic heart failure with preserved ejection fraction. Martin, N., Manoharan, K., Thomas, J., et al.[2023]

Comprehensive therapy using a combination of ARNI, β blockers, MRAs, and SGLT2 inhibitors significantly reduces the risk of cardiovascular death and hospital admissions for heart failure compared to conventional therapy, with a hazard ratio of 0.38 for the primary endpoint.

Patients receiving comprehensive therapy can expect substantial gains in event-free survival, with estimates of 2.7 to 8.3 additional years free from cardiovascular events and 1.4 to 6.3 additional years of overall survival, depending on age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estimating lifetime benefits of comprehensive disease-modifying pharmacological therapies in patients with heart failure with reduced ejection fraction: a comparative analysis of three randomised controlled trials. Vaduganathan, M., Claggett, BL., Jhund, PS., et al.[2023]

Aldosterone receptor antagonists, such as spironolactone and eplerenone, are recommended for many heart failure patients to improve treatment outcomes when used alongside ACE inhibitors or ARBs and beta-blockers.

The combination of these medications can enhance heart function and reduce symptoms in heart failure patients, highlighting the importance of a multi-drug approach in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aldosterone receptor antagonists for heart failure: current status, future indications. Pitt, B., Rajagopalan, S.[2019]

Sacubitril/valsartan (Entresto) significantly reduces the risk of cardiovascular death and hospitalization for heart failure by 20% compared to the standard treatment enalapril, based on data from the PARADIGM-HF trial and other studies.

While sacubitril/valsartan is effective for patients with heart failure with reduced ejection fraction, it does carry a risk of hypotension and nonserious angioedema, necessitating careful monitoring by healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A New Mechanism of Action in Heart Failure: Angiotensin-Receptor Neprilysin Inhibition. Richardson, J., David, T., Grace, Y., et al.[2021]

Sacubitril-valsartan significantly reduces the risk of all-cause and cardiovascular mortality in patients with heart failure with reduced ejection fraction (HFrEF), as shown in a meta-analysis of six trials involving 14,959 patients.

While sacubitril-valsartan is associated with a higher risk of symptomatic hypotension, it has a lower risk of worsening renal function and serious hyperkalaemia compared to traditional treatments like enalapril or valsartan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of sacubitril-valsartan in heart failure: a meta-analysis of randomized controlled trials. Zhang, H., Huang, T., Shen, W., et al.[2022]

In a study of 120 patients with heart failure and reduced ejection fraction (HFrEF) in Pakistan, Sacubitril/Valsartan was found to be safe and well-tolerated, with 80.6% of patients able to continue the prescribed dose over 12 weeks.

The treatment led to significant improvements in functional class, with 75% of patients improving to class I, although hyperkalemia (21.3% incidence) and hypotension (19.4% incidence) were noted as safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of Sacubitril/Valsartan in heart failure patient with reduced ejection fraction. Khan, MN., Soomro, NA., Naseeb, K., et al.[2023]

Entresto (Sacubitril/Valsartan) is a newly FDA-approved treatment for Heart Failure with Reduced Ejection Fraction (HFrEF), offering a novel mechanism of action by combining angiotensin receptor blockage and neprilysin inhibition.

This drug represents a significant advancement in heart failure management, providing an alternative to traditional treatments like ACE inhibitors and ARBs, and highlights the ongoing evolution of therapies available for heart failure patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Entresto, a New Panacea for Heart Failure? Khalil, P., Kabbach, G., Said, S., et al.[2021]

A historical review of mortality trials shows that ACE inhibitors and angiotensin II receptor antagonists have been the standard treatment for chronic heart failure, demonstrating their efficacy in improving patient outcomes.

The new dual inhibitor valsartan + neprilysin (LCZ 696) shows promise as a future treatment option, while other approaches like direct renin blockers and dual blockers have proven ineffective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Inhibition of renin-angiotensin-aldosterone system in heart failure, or from CONSENSUS to PARADIGM-HF]. Vítovec, J., Špinar, J., Špinarová, L.[2018]

The combination of valsartan-sacubitril (an ARNI) and empagliflozin (a gliflozin) showed rapid improvement in heart function and clinical markers in an elderly female patient with congestive heart failure and type 2 diabetes, suggesting a beneficial cardio-reno-metabolic approach.

The PARADIGM-HF study demonstrated that valsartan-sacubitril significantly reduces cardiovascular events and mortality in heart failure patients, highlighting its efficacy compared to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Modification of the of the cardiometabolic profile using combined therapy of the angiotensin receptor-neprilysin inhibitor and empagliflozin in comorbid patients with Chronic Heart Failure and type 2 Diabetes Mellitus]. Tsygankova, OV., Veretyuk, VV., Mareev, VY.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Relative Efficacy of Sacubitril-Valsartan, Vericiguat, and SGLT2 Inhibitors in Heart Failure with Reduced Ejection Fraction: a Systematic Review and Network Meta-Analysis. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Beta-blockers and inhibitors of the renin-angiotensin aldosterone system for chronic heart failure with preserved ejection fraction. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Estimating lifetime benefits of comprehensive disease-modifying pharmacological therapies in patients with heart failure with reduced ejection fraction: a comparative analysis of three randomised controlled trials. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Targeting the renin-angiotensin-aldosterone system in heart failure. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Aldosterone receptor antagonists for heart failure: current status, future indications. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

A New Mechanism of Action in Heart Failure: Angiotensin-Receptor Neprilysin Inhibition. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of sacubitril-valsartan in heart failure: a meta-analysis of randomized controlled trials. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Sacubitril/Valsartan (Entresto®)-Induced Hyponatremia. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Safety and tolerability of Sacubitril/Valsartan in heart failure patient with reduced ejection fraction. [2023]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Entresto, a New Panacea for Heart Failure? [2021]

11. Czech Republic pubmed.ncbi.nlm.nih.gov

[Inhibition of renin-angiotensin-aldosterone system in heart failure, or from CONSENSUS to PARADIGM-HF]. [2018]

12. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Modification of the of the cardiometabolic profile using combined therapy of the angiotensin receptor-neprilysin inhibitor and empagliflozin in comorbid patients with Chronic Heart Failure and type 2 Diabetes Mellitus]. [2020]