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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02624765




Registration number
NCT02624765
Ethics application status
Date submitted
30/11/2015
Date registered
8/12/2015
Date last updated
14/08/2019

Titles & IDs
Public title
FAST Therapy Trial of Fetal Tachyarrhythmia
Scientific title
Prospective Randomized Clinical Trial of Fetal Atrial Flutter & Supraventricular Tachycardia (FAST) Therapy
Secondary ID [1] 0 0
1000039945
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fetal Atrial Flutter Without Hydrops 0 0
Fetal Supraventricular Tachycardia Without Hydrops 0 0
Fetal Supraventricular Tachycardia With Hydrops 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Digoxin (monotherapy)
Treatment: Drugs - Sotalol (monotherapy)
Treatment: Drugs - Flecainide (monotherapy)
Treatment: Drugs - Digoxin (dual therapy)
Treatment: Drugs - Sotalol (dual therapy)
Treatment: Drugs - Flecainide (dual therapy)

Active Comparator: RCT A (1st arm): AF without hydrops - Atrial Flutter (AF) without hydrops: Treatment with Digoxin as monotherapy.

Active Comparator: RCT A (2nd arm): AF without hydrops - Atrial Flutter (AF) without hydrops: Treatment with Sotalol as monotherapy.

Active Comparator: RCT B (1st arm): SVT without hydrops - Supraventricular Tachycardia (SVT) without hydrops: Treatment with Digoxin as monotherapy.

Active Comparator: RCT B (2nd arm): SVT without hydrops - Supraventricular Tachycardia (SVT) without hydrops: Treatment with Flecainide as monotherapy.

Active Comparator: RCT C (1st arm): SVT with hydrops - Supraventricular Tachycardia (SVT) with hydrops: Treatment with Digoxin and Sotalol.

Active Comparator: RCT C (2nd arm): SVT with hydrops - Supraventricular Tachycardia (SVT) with hydrops: Treatment with Digoxin and Flecainide.


Treatment: Drugs: 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

Treatment: Drugs: Sotalol (monotherapy)
Oral dose: 80 mg TID or 120 mg BID (240 mg/day)

Treatment: Drugs: Flecainide (monotherapy)
Oral dose: 100 mg TID (300 mg/day)

Treatment: Drugs: 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

Treatment: Drugs: Sotalol (dual therapy)
Oral dose: 160 mg BID (320 mg/day)

Treatment: Drugs: Flecainide (dual therapy)
Oral dose:100 mg TID (300 mg/day)

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of live-born children with a delivery at term and a normal cardiac rhythm
Timepoint [1] 0 0
Term: 37 0/7 to 41 6/7 weeks
Secondary outcome [1] 0 0
Proportion of patients with cardioversion over time - Number of participants with persistent tachycardia compared to number of participants with cardioversion to a normal rhythm over time
Timepoint [1] 0 0
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
Secondary outcome [2] 0 0
Proportion of participants with treatment failure - Number of participants with treatment failure compared to number of participants with successful treatment. Treatment failure is defined as one of the following: 1) cross-over to another drug; 2) SVT/AF that persists to birth; 3) preterm birth; 4) death.
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
Proportion of participants with arrhythmia-related death - Number of participants with arrhythmia-related death compared to other outcomes
Timepoint [3] 0 0
From date of randomization to 30 days of life
Secondary outcome [4] 0 0
Average gestational age at birth
Timepoint [4] 0 0
At birth
Secondary outcome [5] 0 0
Birth weight z-scores
Timepoint [5] 0 0
At birth
Secondary outcome [6] 0 0
Total days of treatment related maternal and neonatal hospitalizations
Timepoint [6] 0 0
From date of randomization to 30 days of life
Secondary outcome [7] 0 0
Maternal prevalence of adverse events and outcome
Timepoint [7] 0 0
From date of randomization to 30 days of life

Eligibility
Key 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
Minimum age
16 Years
Maximum age
50 Years
Gender
Females
Can healthy volunteers participate?
No
Key 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
The Royal Women's Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Utah
Country [10] 0 0
United States of America
State/province [10] 0 0
West Virginia
Country [11] 0 0
United States of America
State/province [11] 0 0
Wisconsin
Country [12] 0 0
Canada
State/province [12] 0 0
Edmonton
Country [13] 0 0
Canada
State/province [13] 0 0
Montreal
Country [14] 0 0
Canada
State/province [14] 0 0
Toronto
Country [15] 0 0
Canada
State/province [15] 0 0
Vancouver
Country [16] 0 0
Germany
State/province [16] 0 0
Bonn
Country [17] 0 0
Netherlands
State/province [17] 0 0
Amsterdam
Country [18] 0 0
Netherlands
State/province [18] 0 0
Leiden
Country [19] 0 0
Netherlands
State/province [19] 0 0
Rotterdam
Country [20] 0 0
Netherlands
State/province [20] 0 0
Utrecht
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Belfast
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Birmingham
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Glasgow
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Liverpool
Country [25] 0 0
United Kingdom
State/province [25] 0 0
London

Funding & Sponsors
Primary sponsor type
Other
Name
Edgar Jaeggi
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Canadian Institutes of Health Research (CIHR)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
St George's, University of London
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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).
Trial website
https://clinicaltrials.gov/show/NCT02624765
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Edgar Jaeggi, MD
Address 0 0
The Hospital for Sick Children, Toronto
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Prachi Sharma, MSc, CCRA
Address 0 0
Country 0 0
Phone 0 0
1-416-813-7654
Fax 0 0
Email 0 0
fast.trial@sickkids.ca
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02624765