FAST RCT: Prospective Randomized Clinical Trial of Fetal Atrial Flutter & Supraventricular Tachycardia Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 105
- 试验地点
- 22
- 主要终点
- Proportion of live-born children with a delivery at term and a normal cardiac rhythm
研究概览
简要总结
The Fetal Atrial Flutter and Supraventricular Tachycardia (FAST) Therapy Trial is a prospective multi-center trial that examines the efficacy and safety of standard prenatal antiarrhythmic treatment. Study components of FAST include three prospective sub-studies to determine the efficacy and safety of commonly used transplacental drug regimens in suppressing fetal AF without hydrops (Randomized Clinical Trial (RCT) A), SVT without hydrops (RCT B), and SVT with hydrops (RCT C). All RCTs are open label phase III trials of standard 1st line therapy, which either is started as monotherapy (no hydrops) or as dual therapy (hydrops).
详细描述
Few studies are specifically designed to address health concerns relevant during pregnancy. The consequence is a lack of evidence on best clinical practice. This includes mothers and their babies when pregnancy is complicated by an abnormally fast heart rate up to 300 beats per minute due to supraventricular tachyarrhythmia (SVA) in the unborn baby (fetus). Although fetal SVA, including atrial flutter (AF) and other forms of supraventricular tachycardia (SVT), is the most common cause of intended in-utero fetal therapy, none of the medication used to date has been evaluated for their effects on the mother and her baby in a randomized controlled trial (RCT). As a consequence, physicians need to make decisions about the management of such pregnancies without any evidence from controlled trials on drug efficacy and safety and no consensus among specialists for the optimal management. The Fetal Atrial Flutter and Supraventricular Tachycardia (FAST) Therapy Trial is a prospective multi-center trial that addresses this knowledge gap to guide future fetal SVA therapy to the best of care. Study components of FAST include three prospective sub-studies to determine the efficacy and safety of commonly used transplacental drug regimens in suppressing fetal AF without hydrops (RCT A), SVT without hydrops (RCT B), and SVT with hydrops (RCT C). All RCTs are open label phase III trials of standard 1st line therapy, which either is started as monotherapy (no hydrops) or as dual therapy (hydrops). The primary study aim is the probability of a normal pregnancy outcome after treatment start with Digoxin or Sotalol (AF without hydrops); Digoxin or Flecainide (SVT without hydrops); and Digoxin plus Sotalol or Digoxin plus Flecainide (SVT with hydrops).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 50 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Mother has provided written informed consent to participate
- •Either fetal AF without hydrops, SVT without hydrops or SVT with hydrops
- •Tachyarrhythmia that is significant enough to justify immediate transplacental pharmacological treatment:
- •Tachycardia ≥ 180 bpm during at least 10% of observation time of 30 minutes or longer
- •Tachycardia ≥ 170 bpm during +100% of time (≤ 30 0/7 weeks of gestation)
- •Tachycardia ≥ 280 bpm (irrespective of SVA duration)
- •SVT with fetal hydrops (irrespective of duration)
- •Gestational age > 12 0/7 weeks and <36 0/7 weeks at time of enrollment
- •Untreated tachycardia at time of enrollment
- •Singleton Pregnancy
- •Healthy mother with ± normal pre-treatment cardiovascular findings:
- •ECG without significant abnormalities (sinus rhythm; QTc ≤ 0.47; PR ≤ 0.2 sec; QRS: ≤ 0.12 sec; isolated PACs or PVCs or isolated complete right bundle branch block allowed)
- •Resting heart rate ≥ 50 bpm
- •Systolic BP ≥ 85 bpm
排除标准
- •AF with hydrops (eligible for FAST Registry only)
- •Any maternal-fetal conditions associated with high odds of premature delivery or death other than tachycardia (e.g. severe IUGR; premature rupture of membrane; life-threatening maternal disease (incl. pre-eclampsia; HELLP syndrome); severe congenital fetal abnormalities (T 13 or 18; surgery or death expected < 1 month)
- •History of significant maternal heart condition (open heart surgery; sick sinus syndrome; channelopathy (long QT, Brugada syndrome); ventricular tachycardia; WPW syndrome; high-degree heart block; cardiomyopathy)
- •Relevant preexisting maternal obstructive airway disease including asthma
- •Current therapy with the following medications:
- •Antiarrhythmic drugs
- •Pentamidine
- •Maternal serum potassium level <3.3 mmol/L / <3.3 mEq/L (at start of treatment)
- •Maternal ionized serum calcium level of <1 mmol/L / <4 mg/dL) or total serum calcium level <2 mmol/L / <8mg/dL (at start of treatment)
- •Maternal serum creatinine level > 97.2 µmol/L (>1.1 mg/dl)
研究组 & 干预措施
RCT A (1st arm): AF without hydrops
Atrial Flutter (AF) without hydrops: Treatment with Digoxin as monotherapy.
干预措施: Digoxin (monotherapy) (Drug)
RCT A (2nd arm): AF without hydrops
Atrial Flutter (AF) without hydrops: Treatment with Sotalol as monotherapy.
干预措施: Sotalol (monotherapy) (Drug)
RCT B (1st arm): SVT without hydrops
Supraventricular Tachycardia (SVT) without hydrops: Treatment with Digoxin as monotherapy.
干预措施: Digoxin (monotherapy) (Drug)
RCT B (2nd arm): SVT without hydrops
Supraventricular Tachycardia (SVT) without hydrops: Treatment with Flecainide as monotherapy.
干预措施: Flecainide (monotherapy) (Drug)
RCT C (1st arm): SVT with hydrops
Supraventricular Tachycardia (SVT) with hydrops: Treatment with Digoxin and Sotalol.
干预措施: Digoxin (dual therapy) (Drug)
RCT C (1st arm): SVT with hydrops
Supraventricular Tachycardia (SVT) with hydrops: Treatment with Digoxin and Sotalol.
干预措施: Sotalol (dual therapy) (Drug)
RCT C (2nd arm): SVT with hydrops
Supraventricular Tachycardia (SVT) with hydrops: Treatment with Digoxin and Flecainide.
干预措施: Digoxin (dual therapy) (Drug)
RCT C (2nd arm): SVT with hydrops
Supraventricular Tachycardia (SVT) with hydrops: Treatment with Digoxin and Flecainide.
干预措施: Flecainide (dual therapy) (Drug)
结局指标
主要结局
Proportion of live-born children with a delivery at term and a normal cardiac rhythm
时间窗: Term: 37 0/7 to 41 6/7 weeks
Term delivery (≥37 0/7 weeks gestation) with a normal cardiac rhythm (ECG).
次要结局
- Proportion of patients with cardioversion over time(From date of randomization until the date of first documented cardioversion or until the date of delivery/fetal death without cardioversion, whichever comes first, assessed up to 30 gestational weeks)
- Proportion of participants with treatment failure(From date of randomization until the date of first documented fetal cardioversion or until the date of treatment failure, whichever comes first, assessed up to 30 gestational weeks)
- Proportion of participants with arrhythmia-related death(From date of randomization to 30 days of life)
- Average gestational age at birth(At birth)
- Birth weight z-scores(At birth)
- Total days of treatment related maternal and neonatal hospitalizations(From date of randomization to 30 days of life)
- Maternal prevalence of adverse events and outcome(From date of randomization to 30 days of life)
研究者
Edgar Jaeggi
Edgar Jaeggi, MD FRCP (C)
The Hospital for Sick Children