Prospective Randomized Clinical Trial of Fetal Atrial Flutter & Supraventricular Tachycardia Therapy (FAST RCT)

Edgar Jaeggi

Status and phase: Completed; Phase 3

Conditions: Fetal Supraventricular Tachycardia With Hydrops; Fetal Atrial Flutter Without Hydrops; Fetal Supraventricular Tachycardia Without Hydrops

Treatments: Drug: Flecainide (monotherapy); Drug: Digoxin (monotherapy); Drug: Digoxin (dual therapy); Drug: Flecainide (dual therapy); Drug: Sotalol (monotherapy); Drug: Sotalol (dual therapy)

Study type: Interventional

Funder types: Other

Identifiers

NCT02624765

1000039945

Details and patient eligibility

About

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).

Full 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).

Enrollment: 105 patients

Sex: Female

Ages: 16 to 50 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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105 participants in 6 patient groups

RCT A (1st arm): AF without hydrops

Active Comparator group

Description:

Atrial Flutter (AF) without hydrops: Treatment with Digoxin as monotherapy.

Treatment:

Drug: Digoxin (monotherapy)

RCT A (2nd arm): AF without hydrops

Active Comparator group

Description:

Atrial Flutter (AF) without hydrops: Treatment with Sotalol as monotherapy.

Treatment:

Drug: Sotalol (monotherapy)

RCT B (1st arm): SVT without hydrops

Active Comparator group

Description:

Supraventricular Tachycardia (SVT) without hydrops: Treatment with Digoxin as monotherapy.

Treatment:

Drug: Digoxin (monotherapy)

RCT B (2nd arm): SVT without hydrops

Active Comparator group

Description:

Supraventricular Tachycardia (SVT) without hydrops: Treatment with Flecainide as monotherapy.

Treatment:

Drug: Flecainide (monotherapy)

RCT C (1st arm): SVT with hydrops

Active Comparator group

Description:

Supraventricular Tachycardia (SVT) with hydrops: Treatment with Digoxin and Sotalol.

Treatment:

Drug: Digoxin (dual therapy)

Drug: Sotalol (dual therapy)

RCT C (2nd arm): SVT with hydrops

Active Comparator group

Description:

Supraventricular Tachycardia (SVT) with hydrops: Treatment with Digoxin and Flecainide.

Treatment:

Drug: Digoxin (dual therapy)

Drug: Flecainide (dual therapy)