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

NCT ID: NCT02624765

Last Updated: 2024-05-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2024-03-31

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).

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RCT A (1st arm): AF without hydrops

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

Group Type: ACTIVE_COMPARATOR

Digoxin (monotherapy)

Intervention Type: DRUG

Oral or IV loading dose: 0.5 mg q 12 h (total 4 doses over 48 hours) followed by Oral maintenance dose: 0.25 mg-1mg/day

RCT A (2nd arm): AF without hydrops

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

Group Type: ACTIVE_COMPARATOR

Sotalol (monotherapy)

Intervention Type: DRUG

Oral dose: 80 mg TID or 120 mg BID (240 mg/day)

RCT B (1st arm): SVT without hydrops

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

Group Type: ACTIVE_COMPARATOR

Digoxin (monotherapy)

Intervention Type: DRUG

Oral or IV loading dose: 0.5 mg q 12 h (total 4 doses over 48 hours) followed by Oral maintenance dose: 0.25 mg-1mg/day

RCT B (2nd arm): SVT without hydrops

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

Group Type: ACTIVE_COMPARATOR

Flecainide (monotherapy)

Intervention Type: DRUG

Oral dose: 100 mg TID (300 mg/day)

RCT C (1st arm): SVT with hydrops

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

Group Type: ACTIVE_COMPARATOR

Digoxin (dual therapy)

Intervention Type: DRUG

Oral or IV loading dose: 0.5 mg q 8 h (total 4 doses over 32 hours) followed by oral maintenance dose: 0.25 mg-1mg/day

Sotalol (dual therapy)

Intervention Type: DRUG

Oral dose: 160 mg BID (320 mg/day)

RCT C (2nd arm): SVT with hydrops

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

Group Type: ACTIVE_COMPARATOR

Digoxin (dual therapy)

Intervention Type: DRUG

Oral or IV loading dose: 0.5 mg q 8 h (total 4 doses over 32 hours) followed by oral maintenance dose: 0.25 mg-1mg/day

Flecainide (dual therapy)

Intervention Type: DRUG

Oral dose:100 mg TID (300 mg/day)

Interventions

Digoxin (monotherapy)

Oral or IV loading dose: 0.5 mg q 12 h (total 4 doses over 48 hours) followed by Oral maintenance dose: 0.25 mg-1mg/day

Intervention Type: DRUG

Sotalol (monotherapy)

Oral dose: 80 mg TID or 120 mg BID (240 mg/day)

Intervention Type: DRUG

Flecainide (monotherapy)

Oral dose: 100 mg TID (300 mg/day)

Intervention Type: DRUG

Digoxin (dual therapy)

Oral or IV loading dose: 0.5 mg q 8 h (total 4 doses over 32 hours) followed by oral maintenance dose: 0.25 mg-1mg/day

Intervention Type: DRUG

Sotalol (dual therapy)

Oral dose: 160 mg BID (320 mg/day)

Intervention Type: DRUG

Flecainide (dual therapy)

Oral dose:100 mg TID (300 mg/day)

Intervention Type: DRUG

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)

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Edgar Jaeggi

OTHER

Sponsor Role: lead

Responsible Party

Edgar Jaeggi

Edgar Jaeggi, MD FRCP (C)

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Edgar Jaeggi, MD

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children, Toronto

Locations

UCSF Benioff Children's Hospital

San Francisco, California, United States

Children's Hospital of Colorado

Aurora, Colorado, United States

Children's National Health System

Washington D.C., District of Columbia, United States

Morgan Stanley Children's Hospital of New York-Presbyterian

New York, New York, United States

Cohen Children's Medical Center

New York, New York, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Pediatrix Medical Services, Inc,

Austin, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

West Virginia University Research Corporation

Morgantown, West Virginia, United States

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

The Royal Women's Hospital

Melbourne, Victoria, Australia

University of Alberta/WCCHN

Edmonton, Alberta, Canada

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

Mount Sinai Hospital

Toronto, Ontario, Canada

The Hospital for Sick Children

Toronto, Ontario, Canada

CHU Sainte-Justine Hospital

Montreal, Quebec, Canada

UKB Universitätsklinikum BONN

Bonn, , Germany

Academic Medical Center - AMC

Amsterdam, , Netherlands

Leiden University Medical Center - LUMC

Leiden, , Netherlands

St George's University Hospital Foundation Trust

London, , United Kingdom

Countries

United States; Australia; Canada; Germany; Netherlands; United Kingdom

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1000039945

Identifier Type: -

Identifier Source: org_study_id