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Effect of Ivabradine in Stage D HF/Cardiogenic Shock Patients on Dobutamine

Primary Purpose

Heart Failure, Cardiogenic Shock, Tachycardia

Status
Unknown status
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Ivabradine
Placebo
Sponsored by
Loyola University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Provide written informed consent for the study
  • Have current diagnosis of Ischemic and/or non-ischemic cardiomyopathy
  • Left ventricular ejection fraction (LVEF) < 30% by echo during the screening
  • Sinus rhythm with HR ≥100 bpm
  • Systolic blood pressure ≥ 90 mmHg assessed by cuff sphygmomanometer
  • CI < 2.2 L/min/m2
  • Current symptom(s) of HF (New York Heart Association (NYHA) class IV) at Screening.
  • Absence of hypovolemia, defined as a central venous pressure ≥10 mmHg and pulmonary capillary occlusion pressure ≥15 mmHg before administration of Dobutamine

Exclusion Criteria:

  • Respiratory support with mechanical ventilation
  • Circulatory mechanical support
  • Atrial pacing with the presence of sick sinus syndrome or sino-atrial block
  • Second or third degree atrioventricular (AV) block,
  • Atrial fibrillation/flutter
  • Amiodarone treatment
  • Ventricular tachycardia
  • Acute coronary syndrome
  • Bilirubin > 2.5
  • Alanine aminotransferase (ALT) >60 IE/L,
  • Serum creatinine >2.5 g/ml)
  • Fever and significant infection
  • Pregnancy
  • Anemia, Hgb < 9.0
  • Patients required treated with severe cytochrome CYP3A4 inhibitors drugs Concomitant use of strong CYP3A4 inhibitors will be avoided during the study period

Sites / Locations

  • Loyola University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Ivabradine

Placebo

Arm Description

Initiation at dose 5 mg PO x 1 dose and further increased in 12 hours to 7.5 mg PO twice per day if patient is stable with mean BP≥ 60 mmHg, systolic blood pressure ≥ 90 mmHg and HR ≥100 bpm

Matching placebo given PO twice per day

Outcomes

Primary Outcome Measures

Heart rate
Heart rate will be measured and any changes noted

Secondary Outcome Measures

cardiac index
cardiac index will be assessed by pulmonary artery catheter and any changes noted
plasma brain natriuretic peptide (BNP) level
Labs will be drawn for plasma BNP blood test and any changes noted

Full Information

First Posted
December 15, 2017
Last Updated
May 21, 2019
Sponsor
Loyola University
Collaborators
Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT03387605
Brief Title
Effect of Ivabradine in Stage D HF/Cardiogenic Shock Patients on Dobutamine
Official Title
Effect of Ivabradine on Heart Rate and Hemodynamics in Patients With Stage D Heart Failure (HF)/Cardiogenic Shock on Dobutamine Treatment
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Unknown status
Study Start Date
March 15, 2018 (Actual)
Primary Completion Date
January 2020 (Anticipated)
Study Completion Date
June 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Loyola University
Collaborators
Amgen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a randomized, double blind, single center trial to study of the effects of Ivabradine vs. Placebo on patients hospitalized for Stage D heart failure (HF)/ and cardiogenic shock (CS) who will require continuous infusion of Dobutamine and have developed sinus tachycardia (ST) (heart rate >100 beats/min). The aim of the study will be to assess the potential of Ivabradine to slow ST and improve hemodynamics in patients with stage D HF/CS on Dobutamine treatment.
Detailed Description
This study will explore the hypothesis that Ivabradine will decrease heart rate (HR) and improve hemodynamics in patients with advanced HF on inotropic treatment. This is a randomized, double blind, single center trial will include 40 consecutive patients admitted for Stage D HF/ CS who will require continuous infusion of Dobutamine and will develop ST (HR >100 beats/min). Eligible patients will be randomized (1:1) using blocked randomization with random block sizes of 2 or 4 to start Ivabradine versus placebo. The procedure of randomization to receive either Ivabradine or placebo twice daily will be performed by computerized sequence generation. The hospital pharmacies will be responsible for drug randomization and dispensing, and the investigators and the patients will be blinded to the treatment option. Ivabradine will be started 3 hours after Dobutamine initiation at dose 5 mg and further increased in 12 hours to 7.5 mg bid if patient is stable with mean BP≥ 60 mmHg, systolic blood pressure ≥ 90 mmHg and HR ≥100 bpm. Increase of Ivabradine dosage will be individually stopped for reasons of safety if three episodes of minimal HRs of less than 70 beats per minute, or a drop in mean blood pressure < 60 mmHg or systolic blood pressure < 80 mmHg occur. HR, blood pressure and invasive hemodynamics will be monitored, along with standard right heart cath and echocardiogram measurements obtained. Patients will be followed for a total of 72 hours. The adverse events that will be collected include bradycardia, defined as a heart rate less than 70 bpm, hypotension defined as a systolic blood pressure less than 80 mmHg and any side effect requiring drug discontinuation or dose adjustment. Review of laboratory including renal, hepatic and hematologic counts will be reviewed for any significant changes due to the use of Ivabradine.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Cardiogenic Shock, Tachycardia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Randomized, Double Blind, Placebo Controlled single center study.
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ivabradine
Arm Type
Active Comparator
Arm Description
Initiation at dose 5 mg PO x 1 dose and further increased in 12 hours to 7.5 mg PO twice per day if patient is stable with mean BP≥ 60 mmHg, systolic blood pressure ≥ 90 mmHg and HR ≥100 bpm
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo given PO twice per day
Intervention Type
Drug
Intervention Name(s)
Ivabradine
Other Intervention Name(s)
Corlanor
Intervention Description
ivabradine or placebo given orally 2 times daily for 72 hours
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
matching placebo given 2 times daily for 72 hours
Primary Outcome Measure Information:
Title
Heart rate
Description
Heart rate will be measured and any changes noted
Time Frame
72 hours
Secondary Outcome Measure Information:
Title
cardiac index
Description
cardiac index will be assessed by pulmonary artery catheter and any changes noted
Time Frame
72 hours
Title
plasma brain natriuretic peptide (BNP) level
Description
Labs will be drawn for plasma BNP blood test and any changes noted
Time Frame
72 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Provide written informed consent for the study Have current diagnosis of Ischemic and/or non-ischemic cardiomyopathy Left ventricular ejection fraction (LVEF) < 30% by echo during the screening Sinus rhythm with HR ≥100 bpm Systolic blood pressure ≥ 90 mmHg assessed by cuff sphygmomanometer CI < 2.2 L/min/m2 Current symptom(s) of HF (New York Heart Association (NYHA) class IV) at Screening. Absence of hypovolemia, defined as a central venous pressure ≥10 mmHg and pulmonary capillary occlusion pressure ≥15 mmHg before administration of Dobutamine Exclusion Criteria: Respiratory support with mechanical ventilation Circulatory mechanical support Atrial pacing with the presence of sick sinus syndrome or sino-atrial block Second or third degree atrioventricular (AV) block, Atrial fibrillation/flutter Amiodarone treatment Ventricular tachycardia Acute coronary syndrome Bilirubin > 2.5 Alanine aminotransferase (ALT) >60 IE/L, Serum creatinine >2.5 g/ml) Fever and significant infection Pregnancy Anemia, Hgb < 9.0 Patients required treated with severe cytochrome CYP3A4 inhibitors drugs Concomitant use of strong CYP3A4 inhibitors will be avoided during the study period
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Eugenia Raichlin, MD
Phone
708 327-2738
Email
Eugenia.Raichlin@lumc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Max Liebo, MD
Phone
708 327-2738
Email
mliebo@lumc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eugenia Raichlin, MD
Organizational Affiliation
Loyola University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Loyola University Medical Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eugenia Raichlin, MD

12. IPD Sharing Statement

Plan to Share IPD
No
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Links:
URL
http://medicontenidosporcile.files.wordpress.com/2016/03/curr-reserch-cardiol.pdf
Description
article: Safety, tolerability and efficacy of ivabradine for control of sinus tachycardia in patients undergoing inotropic therapy

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Effect of Ivabradine in Stage D HF/Cardiogenic Shock Patients on Dobutamine

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