Trial Assessing the Effectiveness of Ivabradine Started at Discharge From the Observation Unit

• Status: Unknown status
• Trial end date: 2020-06-30
• Target enrollment: 0
• Participant gender: All

Summary

Ivabradine (IVA) has been shown to decrease the risk of hospitalizations for worsening Heart Failure and was associated with a trend towards improved mortality in the SHIFT1 trial. SHIFT1 excluded patients within 4 weeks of hospital discharge, so the efficacy and safety of IVA in this setting is less clear.

In today's health care environment more and more patients that present to the Emergency Department (ED) for mild Acute Heart Failure (AHF) are being placed into observation unit and subsequently discharged, or discharged outright from the ED. This is not only a growing segment of patients, but also represents an important window of opportunity to intervene with a potentially effective therapy.

Moreover, at this point in a patient's experience (being discharged after getting treated for exacerbation of Heart Failure), it's not clear that beta blockers (BB) should yet be increased/started due to the recent state of exacerbation.

Standard treatment of worsened heart failure presenting to the ED or urgent care includes diuretics (e. g. furosemide) and vasodilators (e.g. ACE-I, ARB, Hydralazine/Isosorbide or ARNi), but according to usual standard of care, titration of beta blockade is often reserved for outpatient follow up after a period of demonstrated stability (in the ambulatory setting).

This is in contradistinction to hospitalized patients, where patients have been observed by the treating team for days, presumably show stability and improvement, and starting low dose BB at the time of hospital discharge has been shown to be safe. As such these ED/Observation discharge patients are often not optimal candidates for intensification of BB at the time of release, and could be considered to be at maximally tolerated BB dose (for at least for 2-4 weeks). This may represent a vulnerable period for these patients; its unknown in the setting of Observation discharge but evidence from hospitalized patients indicates that the highest daily risk of rehospitalization is in the days just after discharge. IVA may be effective post observation unit management (where lower risk Heart Failure (HF) patients are typically placed), to reduce heart rate (without decreasing contractility, such as a BB would) to help reduce the risk of hospitalization or emergency care, but safety and efficacy (in terms of heart rate lowering) in this setting has not been previously explored.

Additionally, the SHIFT1 trial lacked African Americans and this unique patient population has not been previously studied with IVA. The investigating sites serve a predominantly African American patient population. Therefore the proposed study represents an important opportunity to gather data on IVA effect in this understudied group of patients.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Phillip Levy
• Collaborators: Amgen; iRhythm Technologies, Inc.

Criteria

Inclusion Criteria:

1. Age >18 and <90.

2. Established HF with reduced ejection fraction (EF ≤35 %), assessment done within 12 months of index visit.

3. Admitted under observation unit for management of AHF.

4. Heart rate ≥70 beats per minute, with sinus rhythm.

5. Receiving guideline based medical therapy in the judgement of the treating physician.

6. Patient currently on a Beta Blocker regimen. Achieved clinically determined stabilization during treatment under observation unit such that the treating physician is planning to discharge home without hospital admission.

Exclusion Criteria:

1. Known intolerance to study drug.

2. End stage renal disease.

3. Plan to titrate BB at the time of discharge from the observation unit.

4. Any condition that in the opinion of the investigators will interfere with the ability to complete the study (e.g. history of extreme non-adherence, extreme psychosocial instability).

5. Inability to provide written informed consent.

6. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (women of childbearing age will be included only if they agree to use adequate contraceptive methods or engage in sexual abstinence).

7. Systolic Blood pressure less than 100 mmHg.

8. Sick sinus syndrome, sinoatrial block or 3rd degree AV block, unless a functioning demand pacemaker is present.

9. Severe hepatic impairment.

10. Pacemaker dependence (i.e. heart rate maintained exclusively by the pacemaker).

11. Concomitant use of strong CYP3A4 inhibitors. Examples of strong CYP3A4 inhibitors include azole antifungals (e.g., itraconazole), macrolide antibiotics (e.g., clarithromycin, telithromycin), HIV protease inhibitors (e.g., nelfinavir), and nefazodone.

12. Concomitant use of diltiazem or verapamil that are not planned for discontinuation.

13. Severe, left sided valvular abnormalities (severe aortic stenosis, severe mitral stenosis, severe aortic insufficiency or severe mitral regurgitation.

14. Documented, prior to or at the time of randomization, restrictive amyloid cardiomyopathy, or acute myocarditis, or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy.