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

NCT02624765 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: 1000039945
• Study Type: interventional
• Target: 105
• Locations: 6 countries
• Sites: 22

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).

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

Outcome Measures

Primary Outcomes (1)

• Proportion of live-born children with a delivery at term and a normal cardiac rhythm

  Term delivery (≥37 0/7 weeks gestation) with a normal cardiac rhythm (ECG).

  Term: 37 0/7 to 41 6/7 weeks

Secondary Outcomes (7)

• 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

Study Arms (6)

RCT A (1st arm): AF without hydrops

ACTIVE COMPARATOR

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

Drug: Digoxin (monotherapy)

RCT A (2nd arm): AF without hydrops

ACTIVE COMPARATOR

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

Drug: Sotalol (monotherapy)

RCT B (1st arm): SVT without hydrops

ACTIVE COMPARATOR

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

Drug: Digoxin (monotherapy)

RCT B (2nd arm): SVT without hydrops

ACTIVE COMPARATOR

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

Drug: Flecainide (monotherapy)

RCT C (1st arm): SVT with hydrops

ACTIVE COMPARATOR

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

Drug: Digoxin (dual therapy); Drug: Sotalol (dual therapy)

RCT C (2nd arm): SVT with hydrops

ACTIVE COMPARATOR

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

Drug: Digoxin (dual therapy); Drug: Flecainide (dual therapy)

Interventions

Digoxin (monotherapy) 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 (1st arm): AF without hydrops; RCT B (1st arm): SVT without hydrops

Sotalol (monotherapy) DRUG

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

RCT A (2nd arm): AF without hydrops

Flecainide (monotherapy) DRUG

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

RCT B (2nd arm): SVT without hydrops

Digoxin (dual therapy) 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

RCT C (1st arm): SVT with hydrops; RCT C (2nd arm): SVT with hydrops

Sotalol (dual therapy) DRUG

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

RCT C (1st arm): SVT with hydrops

Flecainide (dual therapy) DRUG

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

RCT C (2nd arm): SVT with hydrops

Eligibility Criteria

• Age: 16 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Edgar Jaeggi: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (22)

UCSF Benioff Children's Hospital

San Francisco, California, 94158, United States

Location

Children's Hospital of Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Health System

Washington D.C., District of Columbia, 20010, United States

Location

Morgan Stanley Children's Hospital of New York-Presbyterian

New York, New York, 10032, United States

Location

Cohen Children's Medical Center

New York, New York, 269-01, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Pediatrix Medical Services, Inc,

Austin, Texas, 78722, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

West Virginia University Research Corporation

Morgantown, West Virginia, 26506, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

The Royal Women's Hospital

Melbourne, Victoria, Australia

Location

University of Alberta/WCCHN

Edmonton, Alberta, Canada

Location

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3N1, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, Canada

Location

CHU Sainte-Justine Hospital

Montreal, Quebec, Canada

Location

UKB Universitätsklinikum BONN

Bonn, Germany

Location

Academic Medical Center - AMC

Amsterdam, Netherlands

Location

Leiden University Medical Center - LUMC

Leiden, Netherlands

Location

St George's University Hospital Foundation Trust

London, United Kingdom

Location

MeSH Terms

Interventions

Digoxin; Sotalol; Flecainide

Intervention Hierarchy (Ancestors)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Edgar Jaeggi, MD

  The Hospital for Sick Children, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Edgar Jaeggi, MD FRCP (C)

Study Record Dates

• First Submitted: November 30, 2015
• First Posted: December 8, 2015
• Study Start: February 1, 2016
• Primary Completion: March 31, 2024
• Study Completion: March 31, 2024
• Last Updated: May 22, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); NL (2); GB (1); AU (1); US (12); CA (5)