Use of the Cardioprotectant Dexrazoxane During Congenital Heart Surgery
2021年8月2日 更新者：Daniel Stromberg、University of Texas at Austin
Cardiopulmonary bypass and arrest of the heart during cardiac surgery are necessary to allow the surgeon to perform heart operations. However, these processes can cause injury to the heart which may worsen post-operative outcomes. In fact, the effects of these injuries may continue after surgery, and lead to a long-term decrease in heart function. Neonates and young infants are at particular risk for this occurrence.
While much research has been done in adults looking for medicines that might protect the heart during surgery, few studies have been conducted in neonates and young infants. The investigators are testing Dexrazoxane, which has proven to be cardio-protective in pediatric cancer patients, in the hope that it may lessen cardiac injury during and after congenital heart surgery, and thereby improve outcomes in the neonatal and young infant population.
In order to accomplish this, the investigators must first determine how Dexrazoxane can be safely administered to young children with congenital heart disease.
調査の概要
詳細な説明
Neonates and infants undergoing heart surgery with cardiopulmonary bypass and cardioplegic arrest experience both inflammation and myocardial ischemia-reperfusion [IR] injury. These processes provoke myocardial apoptosis and oxygen free radical formation which result in cardiac injury and dysfunction. Dexrazoxane [DRZ] is a derivative of EDTA that is approved for prevention of anthracycline-related cardiotoxicity. It provides cardioprotection through reduction of toxic reactive oxygen species [ROS], and suppression of apoptosis.
The investigators propose a 12-patient pilot to determine DRZ pharmacokinetics, and to collect additional safety data in the neonatal and infant population. Efficacy of cardioprotection will not be evaluated in this preliminary investigation, though the investigators will determine postoperative time to resolution of organ failure, development of low cardiac output syndrome, length of cardiac ICU and hospital stays, laboratory indices of myocardial injury and systemic inflammation, and echocardiographic cardiac dysfunction for safety purposes, and as a run-in to the larger, randomized, placebo controlled trial. Conducting this pilot could optimize team execution of the study protocol. In addition, results could further establish the safety of DRZ in the neonatal and infant populations.
研究の種類
介入
入学 (予想される)
12
段階
- フェーズ 1
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：Daniel Stromberg, MD
- 電話番号：512-324-3357
- メール：dstromberg@austin.utexas.edu
研究連絡先のバックアップ
- 名前：Jacob Strelow, MPH
- 電話番号：757-268-2691
- メール：strelow.jacob@austin.utexas.edu
研究場所
-
-
Texas
-
Austin、Texas、アメリカ、78723
- 募集
- Dell Children's Medical Center of Central Texas
-
-
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
1秒～1年 (子)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria:
- age ≤ 1 year
- open heart surgery requiring CPB and use of cardioplegia
- parent/guardian consent for study obtained
- surgery planned Monday-Friday
Exclusion Criteria:
- gestational age <36 weeks at time of enrollment
- known syndrome or genetic abnormality, except Trisomy 21
- single ventricle physiology
- concurrent enrollment in another research protocol
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Dexrazoxane
|
Twelve enrollees will be consecutively assigned to a dosing regimen of 400 mg/m2/dose.
The medication will be administered in the operating room 30 minutes prior to starting cardiopulmonary bypass (dose #1), prior to aortic cross clamp removal (dose #2), and on the morning after surgery in the cardiac intensive care unit (dose #3).
他の名前：
|
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 |
|---|---|---|
|
ピーク血漿濃度 (Cmax)
時間枠：24時間
|
24時間
|
|
|
Area under the plasma concentration vs time curve (AUC)
時間枠：24 hours
|
24 hours
|
|
|
Minimum plasma concentration (Cmin)
時間枠：24 hours
|
24 hours
|
|
|
Time to resolution of organ failure
時間枠：14 days
|
defined as hours to the point of being off invasive mechanical ventilation, without significant renal dysfunction [cystatin C within normal range for age, and UOP > 1 cc/kg/hr], and off significant inotropic support [defined as milrinone >0.3 mcg/kg/min, dopamine >3 mcg/kg/min, dobutamine >3 mcg/kg/min, any combination of these inotropes, or any epinephrine, norepinephrine, phenylephrine or vasopressin)] with a serum lactate <2 mmol/L.
One point will be awarded for each postoperative hour of continued organ dysfunction up to postoperative hour 336 (day 14).
A score of 360 will be assigned if organ failure is not resolved by postoperative day 14, or if the patient requires mechanical circulatory support or experiences mortality.
This variable has been chosen to allow for recognition of early drug effects, and those which might be delayed beyond the immediate postoperative period.
|
14 days
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Myocardial Injury
時間枠：7 days
|
determined by elevated serum cardiac troponin
|
7 days
|
|
Oxidative Stress
時間枠：3 days
|
measured by lipoperoxidation (serum F2 isoprostane)
|
3 days
|
|
Inflammatory activation (IL-6 and IL-10)
時間枠：3 days
|
3 days
|
|
|
Neurologic IR injury
時間枠：3 days
|
measured by serum activin A concentration
|
3 days
|
|
ICU Length of Stay
時間枠：60 days
|
60 days
|
|
|
Hospital Length of Stay
時間枠：60 days
|
60 days
|
|
|
Tei Index (via echocardiogram)
時間枠：60 days
|
the sum of the isovolumic contraction and relaxation times divided by the ejection time
|
60 days
|
|
Ventricular ejection fraction (via echocardiogram)
時間枠：60 days
|
the volumetric fraction of fluid ejected from a chamber with each contraction
|
60 days
|
|
Tissue doppler E/E' ratio (via echocardiogram)
時間枠：60 days
|
calculated as E wave divided by e' velocities
|
60 days
|
|
Composite outcome for neonatal cardiac surgery
時間枠：60 days
|
(per Graham, EM, et al) - binary variable defined as death, use of mechanical circulatory support, cardiac arrest requiring chest compressions, hepatic injury [2 times the upper limit of normal for AST or ALT], renal injury [Cr >1.5 mg/dL], or lactic acidosis [an increasing lactate >5 mmol/L in the postoperative period]
|
60 days
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
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研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2021年4月9日
一次修了 (予想される)
2021年10月1日
研究の完了 (予想される)
2022年1月1日
試験登録日
最初に提出
2021年7月21日
QC基準を満たした最初の提出物
2021年8月2日
最初の投稿 (実際)
2021年8月9日
学習記録の更新
投稿された最後の更新 (実際)
2021年8月9日
QC基準を満たした最後の更新が送信されました
2021年8月2日
最終確認日
2021年8月1日
詳しくは
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。