Ivabradine in the Management of Cardiac Autonomic Dysfunction Associated With Thoracic Radiation Therapy.
Condition: Lymphoma; Autonomic Imbalance; Cancer Survivorship
MeSH terms: Autonomic Nervous System Diseases; Primary Dysautonomias
Intervention: Ivabradine; Placebo Oral Tablet
Intervention description: lower heart rate in heart failure patients.; Procedure prescribed to compare the active effect of a medicine.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Lymphoma; Abnormal resting heart rate; Autonomic imbalance; Cancer survivorship

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
    

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.