Predischarge Initiation of Ivabradine in the Management of Heart Failure (PRIME-HF)

NCT02827500 | Completed Phase 4 Results DMC

• 1 other identifier: Pro00071309
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 20

Brief Summary

The PRIME-HF study is a multi-center, patient-level, randomized, open-label study of approximately 450 patients with reduced (left ventricular ejection fraction) LVEF of ≤ 35% and heart-rate ≥70 beats per minute (bpm) who are being discharged from the hospital following stabilization from acute heart failure (HF)(primary or secondary) and will be randomized to a treatment strategy of predischarge initiation of ivabradine or usual care. All participants should have a follow-up visit within 7-14 days of hospital discharge. Heart rate and systolic blood pressure will be assessed at this clinical visit. For participants randomized to predischarge initiation of ivabradine and on ivabradine 5mg BID, the heart rate may be used to adjust the dose the dose to 2.5mg BID or 7.5mg BID. For participants randomized to usual care, ivabradine may be initiated at the provider's discretion. All participants will have a second follow-up study visit 6 weeks (42 +/- 14 days) post-discharge. Heart rate, systolic blood pressure and quality of life (KCCQ and PGA) will be assessed. For participants already taking ivabradine in either treatment group, the heart rate may again be used to adjust the dose of ivabradine. For participants not yet receiving ivabradine, it may be initiated at the provider's discretion. All participants will receive a 90 (+/-7) day post-discharge phone call by site to assess for event status and tolerability of ivabradine. All participants will have a final study visit at 180 (+/-14) days post-discharge. Heart rate, systolic blood pressure and quality of life (Kansas City Cardiomyopathy Questionnaire and Patient Global Assessment) will be assessed. The attending physician may initiate ivabradine per usual care clinical practice. The primary hypothesis of the PRIME-HF study is that, compared with usual care, a treatment strategy of initiation of ivabradine prior to discharge for a hospitalization with acute HF will be associated with a greater proportion of participants using ivabradine at 180 days. Secondary objectives are to assess the impact of predischarge initiation of ivabradine on:Heart Rate (Change in heart rate from baseline to 180 days and Median heart rate at 180 days) and Patient-Centered Outcomes (Kansas City Cardiomyopathy Questionnaire (KCCQ) and Patient Global Assessment (PGA)). Tertiary objectives will be to explore the impact of predischarge initiation of ivabradine on other assessments of evidence-based implementation of ivabradine and beta-blockers at 180 days. Evaluations will incorporate data based on whether or not indication status was retained and whether or not an ivabradine prescription was provided. Tolerability of ivabradine and adverse events during study follow-up.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (1)

• Number of Participants Taking Ivabradine at 180 Days

  180 days

Secondary Outcomes (5)

• Change in Heart Rate

  baseline,180 days

• Heart Rate at 180 Days

  180 days

• Number of Patients With Heart Rate <70 Bpm at 180 Days

  180 days

• Changes in Symptoms and Quality of Life as Measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score

  baseline, 180 days

• Changes in Symptoms and Quality of Life as Measured by Patient Global Assessment (PGA)

  baseline, 180 days

Study Arms (2)

ivabradine

ACTIVE COMPARATOR

Active Comparator: ivabradine

Drug: ivabradine

usual care

PLACEBO COMPARATOR

Placebo Comparator: usual care

Other: Usual Care

Interventions

ivabradine DRUG

Active Comparator: ivabradine

Also known as: Corlanor

ivabradine

Usual Care OTHER

Placebo Comparator: usual care

usual care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Hospitalized with acute HF (primary or secondary diagnosis) based on clinician assessment
• A prior clinical diagnosis of HF (i.e., not a new diagnosis of heart failure during the current hospitalization)
• Most recent LVEF ≤ 35% and within 6 months of randomization or LVEF ≤ 25% within 12 months of randomization
• On optimal guideline-directed medical therapy for HFrEF (or previously deemed intolerant) as determined by the clinician including ACE-inhibitors or angiotensin receptor antagonists or neprilysin inhibition, aldosterone receptor antagonists, and maximally-tolerated doses of beta-blockers at the time of current evaluation (which may differ from long-term targets)
• Maximally-tolerated doses of beta-blockers will be defined by the treating physician when considering aspects such as current dose relative to the target dose used in clinical trials, patient heart rate and blood pressure, and patient symptoms
• Patients with intolerance or contraindication to beta-blocker use are eligible for enrollment (details will be documented in the case report form)
• Age \>18 years
• Willingness to provide informed consent from the subject (or their guardian or legally authorized representative \[LAR\])
• On the day of planned randomization, all participants:
• Must be in sinus rhythm with a resting heart rate \>70 bpm as measured on ECG or 10-second rhythm strip
• Must have a blood pressure of \>90/50 mm Hg

You may not qualify if:

• Documented plan for uptitration of beta-blocker in the following 4 weeks
• Permanent atrial fibrillation or atrial flutter
• Patients with recent atrial fibrillation or flutter defined by either precipitating the current HF hospitalization or occurring during the current HF hospitalization
• History of untreated sick sinus syndrome, sinoatrial block, or second and third degree atrio-ventricular block
• Pacemaker with atrial or ventricular pacing (except biventricular pacing) \>40% of the time
• Family history or congenital long QT syndrome
• Acute or chronic severe liver disease as evidenced by any of the following: encephalopathy, variceal bleeding, INR \> 1.7 in the absence of anticoagulation treatment
• Creatinine clearance \<15 mL/min within 48 hours of screening that was not due to acute kidney injury that resolved
• Planned mechanical circulatory support within 180 days
• Pregnant or breastfeeding women. Women with child-bearing potential should use effective contraception.
• Medical conditions likely to lead to poor non-cardiac survival at 180 days (e.g., cancer)
• Inability to comply with planned study procedures
• Non-dihydropyridine calcium channel blockers (e.g., diltiazem and verapamil)
• Class I anti-arrhythmics (e.g., quinidine, procainamide, lidocaine, phenytoin)
• Strong inhibitors of cytochrome P450 3A4 (CYP3A4), including some macrolide antibiotics (e.g., clarithromycin, erythromycin), cyclosporine, antiretroviral drugs (e.g., ritonavir, nelfinavir), and systemic azole antifungal agents (e.g., ketoconazole, itraconazole), and nefazodone

Sponsors & Collaborators

• Duke University: lead
• Amgen: collaborator

Study Sites (20)

University of Colorado at Denver and Health Sciences Center

Aurora, Colorado, 80045, United States

Location

Holy Cross Hospital

Fort Lauderdale, Florida, 33308, United States

Location

Athens Regional Medical Center

Athens, Georgia, 30606, United States

Location

University Hospital

Augusta, Georgia, 30901, United States

Location

Tanner Medical Center

Carrollton, Georgia, 30117, United States

Location

Midwest Cardiovascular Research

Elkhart, Indiana, 46514, United States

Location

Saint Vincent Medical Group, Inc.

Indianapolis, Indiana, 46260, United States

Location

Great Lakes Heart Center of Alpena

Alpena, Michigan, 49707, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

New York Methodist Hospital

Brooklyn, New York, 11215, United States

Location

Mount Sinai Medical Center

New York, New York, 10029-6574, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Ohio State University- Davis Heart and Lung Research Institute

Columbus, Ohio, 43210, United States

Location

Stern Cardiovascular Foundation

Germantown, Tennessee, 38138, United States

Location

Baylor University Medical Center

Dallas, Texas, 75226, United States

Location

William Beaumont Army Medical Center

El Paso, Texas, 79912, United States

Location

Sentara Norfolk General Hospital

Norfolk, Virginia, 23507, United States

Location

Gundersen Lutheran Medical Center

La Crosse, Wisconsin, 54601, United States

Location

Related Publications (1)

• Mentz RJ, DeVore AD, Tasissa G, Heitner JF, Pina IL, Lala A, Cole RT, Lanfear DD, Patel CB, Ginwalla M, Old W, Salacata AS, Bigelow R, Fonarow GC, Hernandez AF. PredischaRge initiation of Ivabradine in the ManagEment of Heart Failure: Results of the PRIME-HF Trial. Am Heart J. 2020 May;223:98-105. doi: 10.1016/j.ahj.2019.12.024. Epub 2020 Feb 28.

  PMID: 32217365 DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

Ivabradine

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Robert Mentz
• Organization: Duke Clinical Research Institute

robert.mentz@duke.edu

919-668-7121

Study Officials

• Robert Mentz, MD

  Duke Clinical Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2016
• First Posted: July 11, 2016
• Study Start: July 1, 2016
• Primary Completion: October 15, 2018
• Study Completion: October 15, 2018
• Last Updated: October 1, 2019
• Results First Posted: October 1, 2019

Record last verified: 2019-09

Locations

US (20)