BTK阻害剤で治療された被験者における心不整脈の観察研究
Background:
Bruton s tyrosine kinase inhibitors (BTKi) are used to treat a form of leukemia. But taking BTKi can also increase a person s risk of developing an abnormal heart rhythm. This can cause sudden death. In this natural history study, researchers want to learn how BTKi affects the heart.
Objective:
To identify and monitor the effects of BTKi on the heart.
Eligibility:
People aged 18 and older currently receiving or planning to receive BTKi or venetoclax.
Design:
Participants who have not yet started BTKi will have 2 required clinic visits: 1 before they start taking BTKi, and 1 about 6 months later. Participants who are already taking BTKi will have 1 required visit.
Participants will undergo multiple tests:
A physical exam, including collection of blood and saliva.
A test that measures heart activity via stickers placed on the chest.
A test that uses sound waves to capture images of the heart.
An exercise stress test that monitors heart activity and blood pressure while the participant works on a treadmill or stationary bike. Sound wave images of the heart may also be taken while the participant exercises.
Stress magnetic resonance imaging (MRI) may be done in place of an exercise test. Participants will lie on a table that slides into a tube. They will be given drugs to stress the heart while images are taken.
Participants may wear a device to monitor their heart at home.
Participants may have repeat visits if they develop heart symptoms or if they need to stop taking BTKi. They will have follow-up phone calls each year for up to 3 years.
調査の概要
詳細な説明
Study Description:
Pharmacologic therapy with BTK inhibitors (BTKi) is associated with an increased risk of cardiac arrhythmias which can lead to sudden death. There is currently no standard for cardiac screening or monitoring patients on BTKi. We hypothesize that thorough and routine comprehensive cardiac evaluations prior to starting therapy with BTKi and repeated during therapy with BTKi will result in earlier identification of cardiac arrhythmias with the goal of minimizing associated morbidity and mortality. In addition, venetoclax, a different standard therapy for chronic lymphocytic leukemia, has not been associated with increased cardiac adverse events and could serve as a control group.
Objectives:
Primary objective: Identify, monitor, and analyze the arrhythmogenic effects of BTKi as well as sudden death
Secondary objective: Assess the utility of different cardiac tests for identifying and monitoring cardiac arrhythmias in patients receiving BTKi or venetoclax
Exploratory objective: To examine the relationship between the development of cardiac arrhythmias in patients on BTKi as it relates to other variables
Endpoints:
Primary endpoint:
-A composite endpoint of clinically significant cardiac arrhythmias and sudden death in patients starting a BTKi (Cohort A) and in patients already receiving BTKi (Cohort B).
Secondary endpoints:
- Detection of arrhythmias on devices (rest/stress EKG, ambulatory EKG monitor, KardiaMobile)
- Arrhythmia (treatment emergent or worsening) in patients on BTKi
- Sudden death in patients on BTKi
- A composite endpoint of clinically significant cardiac arrhythmias and sudden death in patients starting venetoclax
- Difference in cardiac arrhythmias and sudden death between different BTKi groups (e.g., ibrutinib vs. non-ibrutinib group)
- Difference in cardiac arrhythmias and sudden death between BTKi and venetoclax groups
Exploratory endpoints:
- Pharmacokinetic levels of BTKi
- Duration of BTKi exposure
- Cumulative BTKi dose
- Genetic variants
- Cardiac structural remodeling
- Medical comorbidities
- Concomitant medications
- Substance use
- Identify risk factors or biomarkers for arrhythmia
研究の種類
入学 (推定)
連絡先と場所
研究連絡先
- 名前：Christine E Gruessner, M.D.
- 電話番号：(240) 550-6022
- メール：christine.gruessner@nih.gov
研究連絡先のバックアップ
- 名前：Ingrid C Frey
- 電話番号：(301) 402-0797
- メール：ingrid.frey@nih.gov
研究場所
-
-
Maryland
-
Bethesda、Maryland、アメリカ、20892
- 募集
- National Institutes of Health Clinical Center
-
コンタクト：
- NIH Clinical Center Office of Patient Recruitment (OPR)
- 電話番号：TTY dial 711 800-411-1222
- メール：ccopr@nih.gov
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
Sample size of 135 subjects including men and women over 18 years old followed at the NIH Clinical Center who are either about to start a BTKi (Cohort A) or venetoclax (Cohort C) as well as those already taking BTKi (Cohort B)
説明
- INCLUSION CRITERIA:
To be eligible to participate in this study, an individual must meet all of the following criteria:
- Currently receiving or planning to receive a BTKi or venetoclax.
- Male or female, aged 18 or older
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Ability of subject to understand and the willingness to sign a written informed consent document
EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from participation in this study:
- Any acute cardiac condition including myocardial infarction or decompensated heart failure within the past 3 months
- Pregnancy or lactation- use of BTK inhibitors is contraindicated in pregnant or nursing individuals.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 観測モデル：CASE_CONTROL
- 時間の展望：PROSPECTIVE
コホートと介入
グループ/コホート |
|---|
|
Cohort A
includes all patients prior to starting therapy with a BTKi |
|
Cohort B
includes all patients already on therapy with a BTKi |
|
Cohort C
includes all patients prior to starting therapy with venetoclax |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
arrhythmogenic cardiac effects of BTKi and sudden death within the first 12 months of BTKi therapy
時間枠：12 months
|
1. Clinically significant cardiac arrhythmias while on a BTKi (treatment emergent in those without a history of arrhythmias and worsening of arrhythmia for those with an arrhythmia at the time of enrollment testing) within 12 months. For Cohort A, if a patient has an arrhythmia at the time of baseline testing, only worsening or new arrhythmias will be called an event. For Cohort B, all arrhythmias will be called an event. 2. Sudden death |
12 months
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
tests for identifying and monitoring cardiac arrhythmias in patients receiving BTKi
時間枠：36 months
|
-Detection of arrhythmias on devices (rest EKG, stress EKG, ambulatory EKG monitor, KardiaMobile) -Clinically significant and other arrhythmias (treatment emergent or worsening) in patients on BTKi and on venetoclax -Sudden death -Composite endpoint of clinically significant cardiac arrhythmias and sudden death in patients starting venetoclax -Differences in cardiac arrhythmias and sudden death within BTKi (e.g., ibrutinib vs. non-ibrutinib group) -Differences in cardiac arrhythmias and sudden death between patients on BTKi and venetoclax |
36 months
|
協力者と研究者
捜査官
- 主任研究者：Christine E Gruessner, M.D.、National Heart, Lung, and Blood Institute (NHLBI)
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 10000923
- 000923-H
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。