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

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

Conducting Institutions:

Brigham and Women's Hospital, Massachusetts General Hospital, Children's Hospital Boston, Dana-Farber Cancer Institute

Overall PI:

Tomas Neilan, MD, Massachusetts General Hospital

Site-responsible Investigators:

Anju Nohria, MD, Brigham and Women's Hospital

Ming Hui Chen, MD, Brigham and Women's Hospital

Contacts:

Dana-Farber Cancer Institute: Childrens Hospital Pediatric Clinical Translation Investigation Program CTIP, ctip@partners.org
Massachusetts General Hospital: Cancer Trials Call Center, 877-789-6100
Brigham and Women's Hospital: Anju Nohria, ANOHRIA@PARTNERS.ORG

Eligibility 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.

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