Clinical trial NCT02624765: Prospective Randomized Clinical Trial of Fetal Atrial Flutter & Supraventricular Tachycardia Therapy (FAST RCT)
Official title: FAST RCT: Prospective Randomized Clinical Trial of Fetal Atrial Flutter & Supraventricular Tachycardia Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Fetal Atrial Flutter Without Hydrops
Fetal Supraventricular Tachycardia Without Hydrops
Fetal Supraventricular Tachycardia With Hydrops
Keywords: RCT A: Fetal Atrial Flutter without Hydrops
RCT B: Fetal Supraventricular Tachycardia without Hydrops
RCT C: Fetal Supraventricular Tachycardia with Hydrops
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2015-12-08
Enrollment: 105
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

1. Mother has provided written informed consent to participate
2. Either fetal AF without hydrops, SVT without hydrops or SVT with hydrops
3. 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)
4. Gestational age \> 12 0/7 weeks and \<36 0/7 weeks at time of enrollment
5. Untreated tachycardia at time of enrollment
6. Singleton Pregnancy
7. 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

Exclusion Criteria:

1. AF with hydrops (eligible for FAST Registry only)
2. 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)
3. 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)
4. Relevant preexisting maternal obstructive airway disease including asthma
5. Current therapy with the following medications:

   * Antiarrhythmic drugs
   * Pentamidine
6. Maternal serum potassium level \<3.3 mmol/L / \<3.3 mEq/L (at start of treatment)
7. 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)
8. Maternal serum creatinine level \> 97.2 µmol/L (\>1.1 mg/dl)

Primary outcomes:
measure: Proportion of live-born children with a delivery at term and a normal cardiac rhythm
timeFrame: Term: 37 0/7 to 41 6/7 weeks
Secondary outcomes:
measure: Proportion of patients with cardioversion over time
timeFrame: 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
measure: Proportion of participants with treatment failure
timeFrame: 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
measure: Proportion of participants with arrhythmia-related death
timeFrame: From date of randomization to 30 days of life
measure: Average gestational age at birth
timeFrame: At birth
measure: Birth weight z-scores
timeFrame: At birth
measure: Total days of treatment related maternal and neonatal hospitalizations
timeFrame: From date of randomization to 30 days of life
measure: Maternal prevalence of adverse events and outcome
timeFrame: From date of randomization to 30 days of life
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Benioff Children's Hospital
state: California
city: Aurora
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: Washington
country: United States
facility: Children's National Health System
state: District of Columbia
city: New York
country: United States
facility: Morgan Stanley Children's Hospital of New York-Presbyterian
state: New York
city: New York
country: United States
facility: Cohen Children's Medical Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Pediatrix Medical Services, Inc,
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Morgantown
country: United States
facility: West Virginia University Research Corporation
state: West Virginia
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: Melbourne
country: Australia
facility: The Royal Women's Hospital
state: Victoria
city: Edmonton
country: Canada
facility: University of Alberta/WCCHN
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: CHU Sainte-Justine Hospital
state: Quebec
city: Bonn
country: Germany
facility: UKB Universitätsklinikum BONN
city: Amsterdam
country: Netherlands
facility: Academic Medical Center - AMC
city: Leiden
country: Netherlands
facility: Leiden University Medical Center - LUMC
city: London
country: United Kingdom
facility: St George's University Hospital Foundation Trust
Study officials:
affiliation: The Hospital for Sick Children, Toronto
name: Edgar Jaeggi, MD
role: PRINCIPAL_INVESTIGATOR
References: