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

NCT03137537 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 17-022
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 3

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

Conditions

Lymphoma; Autonomic Imbalance; Cancer Survivorship

Keywords

Lymphoma; Abnormal resting heart rate; Autonomic imbalance; Cancer survivorship

Outcome Measures

Primary Outcomes (1)

• To Investigate Whether Ivabradine Lowers Resting HR, Compared To Placebo, In Survivors Of Lymphoma

  Calculate the change in resting HR (from Holter monitor data) from baseline to 6 weeks for each patient in the study. Then compare the median change with ivabradine to the median change with placebo.

  6 weeks

Secondary Outcomes (1)

• To Evaluate Whether Ivabradine Improves Exercise Duration, Compared To Placebo, In Survivors Of Lymphoma

  6 weeks

Other Outcomes (2)

• To Evaluate Whether Ivabradine Improves Additional Markers of Cardiac Sympatho-vagal Balance, Compared To Placebo, In Survivors Of Lymphoma

  6 weeks

• To Evaluate Whether Ivabradine Improves Health Related Quality Of Life Compared To Placebo, In Survivors Of Lymphoma

  6 weeks

Study Arms (2)

Ivabradine

EXPERIMENTAL

* 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

Placebo Oral Tablet

PLACEBO COMPARATOR

* 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

Interventions

Ivabradine DRUG

lower heart rate in heart failure patients.

Also known as: Corlanor

Ivabradine

Placebo Oral Tablet DRUG

Procedure prescribed to compare the active effect of a medicine.

Placebo Oral Tablet

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Amgen: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston Children Hospital

Boston, Massachusetts, 02115, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Lymphoma

Interventions

Ivabradine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Anju Nohria
• Organization: Dana Farber Cancer Institute

anohria@partners.org

6175257052

Study Officials

• Anju Nohria, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor in Internal Medicine

Study Record Dates

• First Submitted: April 19, 2017
• First Posted: May 2, 2017
• Study Start: February 27, 2018
• Primary Completion: November 18, 2020
• Study Completion: November 18, 2020
• Last Updated: February 10, 2022
• Results First Posted: February 10, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)