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Ivabradine in the Management of Cardiac Autonomic Dysfunction Associated With Thoracic Radiation Therapy.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03137537
Recruitment Status : Recruiting
First Posted : May 2, 2017
Last Update Posted : December 18, 2019
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Anju Nohria, Dana-Farber Cancer Institute

Brief Summary:

This study will explore whether ivabradine lowers heart rate, and thus improves exercise capacity, in survivors of lymphoma who have an elevated resting heart rate as a side effect of prior radiation treatment.

The drugs involved in this study are:

  • Ivabradine
  • Placebo

Condition or disease Intervention/treatment Phase
Lymphoma Autonomic Imbalance Cancer Survivorship Drug: Ivabradine Drug: Placebo Oral Tablet Phase 2

Detailed Description:

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

This research study is a Pilot Study, which is the first time investigators are examining this study intervention for this particular problem.

In this research study, the investigators are studying a drug called ivabradine. The investigators are exploring whether ivabradine can be used to reduce heart rate, increase exercise duration, and improve quality of life in survivors of lymphoma who received radiation to their chest as a part of their cancer treatment.

The U.S. Food and Drug Administration (FDA) has not approved ivabradine for this specific disease, but it has approved the drug as an oral medication to lower heart rate in heart failure patients.

Survivors of lymphoma who were treated with neck and/or chest radiation can have an elevated resting heart rate and an abnormal rate of decline in their heart rate after exercise, also known as cardiac autonomic dysfunction. These abnormalities can limit exercise duration and worsen quality of life in some radiation treated survivors of lymphoma

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Ivabradine in the Management of Cardiac Autonomic Dysfunction Associated With Thoracic Radiation Therapy.
Actual Study Start Date : February 27, 2018
Estimated Primary Completion Date : April 30, 2021
Estimated Study Completion Date : April 30, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Ivabradine

Arm Intervention/treatment
Experimental: Ivabradine
  • Ivabradine will be administered for a total of 6 weeks
  • Ivabradine is taken orally twice daily
  • Dosage will be adjusted according to physician determination
Drug: Ivabradine
lower heart rate in heart failure patients.
Other Name: Corlanor

Placebo Comparator: Placebo Oral Tablet
  • Placebo will be administered for a total of 6 weeks
  • Placebo is taken orally twice daily
  • Dosage will be adjusted according to physician determination
Drug: Placebo Oral Tablet
Procedure prescribed to compare the active effect of a medicine.




Primary Outcome Measures :
  1. To Investigate Whether Ivabradine Lowers Resting HR, Compared To Placebo, In Survivors Of Lymphoma [ Time Frame: 6 weeks ]
    Calculate the change in resting HR (from EKGs) from baseline to 6 weeks for each patient in the study (n=60).


Secondary Outcome Measures :
  1. To Evaluate Whether Ivabradine Improves Exercise Duration, Compared To Placebo, In Survivors Of Lymphoma [ Time Frame: 6 weeks ]
    Calculate the change in exercise duration (from exercise treadmill stress tests) from baseline to 6 weeks for each patient in the study (n=60)


Other Outcome Measures:
  1. To Evaluate Whether Ivabradine Improves Additional Markers of Cardiac Sympatho-vagal Balance, Compared To Placebo, In Survivors Of Lymphoma [ Time Frame: 6 weeks ]
    Calculate the change in cardiac autonomic function (from cardiac autonomic function testing) from baseline to 6 weeks in one half of the patients in the study (n=30)

  2. To Evaluate Whether Ivabradine Improves Health Related Quality Of Life Compared To Placebo, In Survivors Of Lymphoma [ Time Frame: 6 weeks ]
    Calculate the change in health related quality of life (from SF-36 quality of life surveys) from baseline to 6 weeks for each patient in the study (n=60)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Survivors of mediastinal lymphoma (either Non-Hodgkin's Lymphoma or Hodgkin's Lymphoma) with no active malignancy
  • Prior mediastinal or mantle radiation ≥ 5 years prior to enrollment in the study
  • Age 18-80 years.
  • Participants must have normal organ function as defined below:

    • AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
    • creatinine clearance ≥ 15 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
  • Normal sinus rhythm with resting heart rate ≥ 80 bpm on screening EKG
  • Based on findings in animals, ivabradine may cause fetal harm when administered to a pregnant woman. For this reason, women of child-bearing potential must agree to use adequate contraception.
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Participants who are receiving any other investigational agents.
  • History of allergic reaction to ivabradine.
  • Participants receiving any medications or substances that are inhibitors or inducers of cytochrome P450 3A4 are ineligible.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, acute coronary syndrome, symptomatic known coronary artery disease, severe valvular heart disease, active malignancy, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study because ivabradine is an agent with the potential for teratogenic effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ivabradine, breastfeeding should be discontinued if the mother is treated with ivabradine.
  • HIV-positive participants on combination antiretroviral therapy.
  • Patients with systolic blood pressure < 90 mm Hg.
  • Patients with sick-sinus syndrome, sino-atrial block, third degree heart block, atrial fibrillation, and those with permanent pacemakers.
  • Patients with other established indications for ivabradine: stable, symptomatic chronic HF with a left ventricular ejection fraction ≤ 35% and in sinus rhythm with a resting HR ≥ 70 bpm, who are taking maximally tolerated doses of beta-blockers or have contraindications to beta-blocker use.
  • Patients with severe hepatic dysfunction (Child Pugh Class C).
  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03137537


Contacts
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Contact: Anju Nohria, MD 617-525-7052 anohria@bwh.harvard.edu

Locations
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United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Tomas Neilan, MD    617-724-5351      
Principal Investigator: Tomas Neilan, MD         
Boston Children Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Ming Hui Chen, MD    617-355-8539      
Principal Investigator: Ming Hui Chen, MD         
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Anju Nohria, MD    617-525-7052    anohria@bwh.harvard.edu   
Principal Investigator: Anju Nohria, MD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Amgen
Investigators
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Principal Investigator: Anju Nohria, MD Brigham and Women's Hospital
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Responsible Party: Anju Nohria, Assistant Professor in Internal Medicine, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT03137537    
Other Study ID Numbers: 17-022
First Posted: May 2, 2017    Key Record Dates
Last Update Posted: December 18, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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.: Yes
Keywords provided by Anju Nohria, Dana-Farber Cancer Institute:
Lymphoma
Abnormal resting heart rate
Autonomic imbalance
Cancer survivorship
Additional relevant MeSH terms:
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Autonomic Nervous System Diseases
Primary Dysautonomias
Nervous System Diseases