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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03137537
• Other study ID #: 17-022
• Status: Terminated
• Phase: Phase 2
• Start date: February 27, 2018
• Est. completion date: November 18, 2020

Study information

• Verified date: January 2022
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 23
• Est. completion date: November 18, 2020
• Est. primary completion date: November 18, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Autonomic Imbalance
• Autonomic Nervous System Diseases
• Cancer Survivorship
• Lymphoma
• Primary Dysautonomias

Intervention

Drug:
• Ivabradine
lower heart rate in heart failure patients.
• Placebo Oral Tablet
Procedure prescribed to compare the active effect of a medicine.

Locations

Country	Name	City	State
United States	Boston Children Hospital	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	Amgen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To Evaluate Whether Ivabradine Improves Additional Markers of Cardiac Sympatho-vagal Balance, Compared To Placebo, In Survivors Of Lymphoma	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)	6 weeks
Other	To Evaluate Whether Ivabradine Improves Health Related Quality Of Life Compared To Placebo, In Survivors Of Lymphoma	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)	6 weeks
Primary	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	To Evaluate Whether Ivabradine Improves Exercise Duration, Compared To Placebo, In Survivors Of Lymphoma	Calculate the change in exercise duration (from exercise treadmill stress tests) from baseline to 6 weeks for each patient in the study. Then compare the median change in exercise duration with ivabradine to the median change in exercise duration with placebo.	6 weeks