Beta-Blocker Tapering for Cardiac Amyloidosis

Overseen By Princess Osma, BA

Age: 65+

Sex: Any

Trial Phase: Phase 4

Sponsor: Weill Medical College of Cornell University

Must be taking: Beta-blockers

Disqualifiers: Angina, Acute coronary syndrome, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether people with cardiac amyloidosis (a heart condition where abnormal proteins build up in the heart) feel better when they stop taking beta-blockers, a medication that can help with heart issues. Participants will alternate between taking their beta-blocker and not taking it to assess their well-being in each phase. Participant feedback will help refine the process. Those who have had a PYP scan or biopsy confirming cardiac amyloidosis and are currently taking a beta-blocker may be suitable candidates for this study. As a Phase 4 trial, this study involves an FDA-approved treatment and aims to understand its benefits for more patients.

Will I have to stop taking my current medications?

Yes, you will need to stop taking your beta-blocker as part of the trial to see if you feel better without it. The study involves periods where you will be on and off the medication.

What is the safety track record for beta-blockers?

Research has shown that beta-blockers can be effective and safe for some individuals with heart amyloidosis, but not for everyone. One study found that 53% of patients with a specific type of heart amyloidosis tolerated beta-blockers well and experienced longer survival. However, nearly half of the patients did not tolerate them as well. Another review examined how patients with heart amyloidosis managed with beta-blockers. It found that while some patients had no issues, others experienced side effects or did not benefit. Overall, the safety of beta-blockers varies among individuals. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this trial because they're exploring a new approach to managing cardiac amyloidosis by adjusting beta-blocker dosages. Unlike standard treatments that maintain a constant beta-blocker dose, this trial involves a unique on-off sequence where patients gradually decrease their beta-blocker use. This method could reveal whether less beta-blocker is needed to manage symptoms effectively, potentially reducing side effects while still providing the necessary heart support. The trial aims to provide insights into optimizing beta-blocker use for improved patient outcomes.

What evidence suggests that beta-blocker tapering might be an effective treatment for cardiac amyloidosis?

Research has shown that beta-blockers might help people with heart problems caused by amyloidosis. One study found that patients with this condition who took beta-blockers lived longer. Another study discovered that patients with a specific type of this heart condition, called ATTR-CM, had lower death rates when using beta-blockers compared to those who didn't. However, not everyone tolerates beta-blockers well, so their effectiveness can vary. This trial will follow an On-Off sequence to evaluate the effects of tapering beta-blockers in individuals with cardiac amyloidosis, recognizing that while evidence suggests beta-blockers can be beneficial, their effectiveness depends on the individual. ^{1 2 3 4 6}

Who Is on the Research Team?

Parag Goyal, MD, MSc

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

This trial is for ambulatory adults aged 65 or older with TTR-cardiac amyloidosis, confirmed by specific tests, who are currently taking beta-blockers. It's not suitable for those with a life expectancy under 6 months, recent medication changes, severe heart issues in the past 3 years, certain mental health conditions, hospitalization within the last month, or any other condition that makes them unsuitable as per the investigator.

Inclusion Criteria

I am 65 or older and have TTR-cardiac amyloidosis confirmed by a scan or biopsy.

I am currently taking a beta-blocker medication.

Exclusion Criteria

Estimated life expectancy <6 months

I was in the hospital within the last 30 days.

My heart cannot pump blood effectively anymore.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

On Phase (Period 1)

Participants are on their beta-blocker (or the highest dose they can safely tolerate) as previously prescribed by their physician

Up to 6 weeks

Weekly visits for monitoring

Off Phase (Period 2)

Participants down-titrate their beta-blocker by 50% each week until they are completely off the drug (or the lowest dose they can safely tolerate)

Up to 6 weeks

Weekly visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Beta blocker

Trial Overview The study is testing whether patients with cardiac amyloidosis feel better without their usual beta-blocker medication. Participants will alternate between periods of taking and not taking their beta-blocker over two spans of up to six weeks each. The process includes interviews and stakeholder engagement to assess the approach.

How Is the Trial Designed?

Group I: On-Off Sequence Experimental Treatment 1 Intervention

This arm will follow an On-Off sequence. This is the only arm in the study. Subjects will begin in the On phase (Period 1), where they will be on their beta-blocker (or the highest dose they can safely tolerate) as previously prescribed to the subjects by their physician. Subjects will then continue to the Off phase (Period 2) where they will down-titrate their beta-blocker by 50% each week until they are completely off the drug (or the lowest dose they can safely tolerate) for a total of two weeks. At the end of Period 2, the subjects will have their End of Intervention visit to determine if they would like to continue or discontinue their beta-blockers for the foreseeable future.

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

U.S. Deprescribing Research Network

Collaborator

Trials

1

Recruited

20+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39041492/

Effect of beta-blockade on mortality in patients with cardiac ... Conclusions: Treatment with beta-blockers may be associated with a survival benefit in patients with CA, but these findings are subject to ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9309481/

Beta-Adrenergic Antagonist Tolerance in Amyloid ... This study analyzes the incidence and characteristics of BB tolerance in patients with amyloid cardiomyopathy.

3. internationaljournalofcardiology.com internationaljournalofcardiology.com/article/S0167-5273(24)00178-5/abstract

Tolerability and effectiveness of beta-blockers in patients ... This systematic review aimed to assess the tolerability of patients with cardiac amyloidosis (CA) to beta-blockers (BBs) and evaluate its association with ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/ehf2.14975

Effect of beta‐blockade on mortality in patients with cardiac ... The only study that solely included 53 patients with AL-CM, demonstrated improved survival among the 53% who were able to tolerate beta-blocker ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0025619621006248

Beta-Blocker Exposure and Survival in Patients With ... Patients with ATTR-CM who received beta blockers showed statistically significant lower all-cause mortality than untreated controls as evaluated by either ...

6. ahajournals.org ahajournals.org/doi/10.1161/CIR.0000000000000792

Cardiac Amyloidosis: Evolving Diagnosis and Management A phase 2 trial of AG10 demonstrated an acceptable safety profile, and data ... antagonists, or angiotensin receptors blockers–neprilysin ...