Fetal Atrial Flutter Without HydropsPhase 3NCT02624765
Prospective Randomized Clinical Trial of Fetal Atrial Flutter & Supraventricular Tachycardia Therapy (FAST RCT)
A Phase 3 study testing Digoxin (monotherapy), Sotalol (monotherapy) and Flecainide (monotherapy) in people with Fetal Atrial Flutter Without Hydrops and Fetal Supraventricular Tachycardia Without Hydrops, run by Edgar Jaeggi at 22 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 50 years, women only
- Conditions the study is for
- Fetal Atrial Flutter Without Hydrops, Fetal Supraventricular Tachycardia Without Hydrops, Fetal Supraventricular Tachycardia With Hydrops
- What is being tested?
- Digoxin (monotherapy), Sotalol (monotherapy) and Flecainide (monotherapy)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- 22 sitesin 6 countries
- Study dates
- Feb 2016to 31 Mar 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 50 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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)
Trial locations and contacts
22 sites in 6 countries.
22 sites in 6 countries
United States12 sites
Children's Hospital of Colorado
Aurora, Colorado, 80045
Pediatrix Medical Services, Inc,
Austin, Texas, 78722
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Baylor College of Medicine
Houston, Texas, 77030
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
West Virginia University Research Corporation
Morgantown, West Virginia, 26506
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Morgan Stanley Children's Hospital of New York-Presbyterian
New York, New York, 10032
Cohen Children's Medical Center
New York, New York, 269-01
University of Utah
Salt Lake City, Utah, 84112
UCSF Benioff Children's Hospital
San Francisco, California, 94158
Children's National Health System
Washington D.C., District of Columbia, 20010
Canada5 sites
University of Alberta/WCCHN
Edmonton, Alberta
CHU Sainte-Justine Hospital
Montreal, Quebec
Mount Sinai Hospital
Toronto, Ontario
The Hospital for Sick Children
Toronto, Ontario
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3N1
Netherlands2 sites
Academic Medical Center - AMC
Amsterdam
Leiden University Medical Center - LUMC
Leiden
United Kingdom1 site
St George's University Hospital Foundation Trust
London
About this study
Official title: FAST RCT: Prospective Randomized Clinical Trial of Fetal Atrial Flutter & Supraventricular Tachycardia Therapy
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).
Read the 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
- Being tested
- Digoxin (monotherapy), Sotalol (monotherapy), Flecainide (monotherapy), Digoxin (dual therapy), Sotalol (dual therapy)
- Keywords
- RCT A: Fetal Atrial Flutter without Hydrops, RCT B: Fetal Supraventricular Tachycardia without Hydrops, RCT C: Fetal Supraventricular Tachycardia with Hydrops
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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
Sotalol (monotherapy)Drug
Oral dose: 80 mg TID or 120 mg BID (240 mg/day)
Flecainide (monotherapy)Drug
Oral dose: 100 mg TID (300 mg/day)
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
Sotalol (dual therapy)Drug
Oral dose: 160 mg BID (320 mg/day)
Flecainide (dual therapy)Drug
Oral dose:100 mg TID (300 mg/day)
| Study group | Role | What they receive |
|---|---|---|
| RCT A (1st arm): AF without hydrops | Active comparator | Atrial Flutter (AF) without hydrops: Treatment with Digoxin as monotherapy. Receives: Drug: Digoxin (monotherapy) |
| RCT A (2nd arm): AF without hydrops | Active comparator | Atrial Flutter (AF) without hydrops: Treatment with Sotalol as monotherapy. Receives: Drug: Sotalol (monotherapy) |
| RCT B (1st arm): SVT without hydrops | Active comparator | Supraventricular Tachycardia (SVT) without hydrops: Treatment with Digoxin as monotherapy. Receives: Drug: Digoxin (monotherapy) |
| RCT B (2nd arm): SVT without hydrops | Active comparator | Supraventricular Tachycardia (SVT) without hydrops: Treatment with Flecainide as monotherapy. Receives: Drug: Flecainide (monotherapy) |
| RCT C (1st arm): SVT with hydrops | Active comparator | Supraventricular Tachycardia (SVT) with hydrops: Treatment with Digoxin and Sotalol. Receives: 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. Receives: Drug: Digoxin (dual therapy); Drug: Flecainide (dual therapy) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Term: 37 0/7 to 41 6/7 weeks
Secondary outcomes (7)
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
Measured: 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
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.
Measured: 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
Number of participants with arrhythmia-related death compared to other outcomes
Measured: From date of randomization to 30 days of life
Average gestational age at birth
Mean of the gestational age at birth
Measured: At birth
Birth weight z-scores
A birth weight z-score compares a child's birth weight to the weight of a child of the same length/height and gender to classify nutritional status
Measured: At birth
Total days of treatment related maternal and neonatal hospitalizations
Average days of maternal and neonatal hospitalization related to SVA therapy
Measured: From date of randomization to 30 days of life
Maternal prevalence of adverse events and outcome
Maternal prevalence of pregnancy/treatment-related AEs and outcomes
Measured: From date of randomization to 30 days of life
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2015 (estimated)
- Study startFeb 2016
- Primary completion31 Mar 2024
- Study completion31 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fetal Atrial Flutter Without HydropsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- Edgar Jaeggi
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor-investigator, Edgar Jaeggi, The Hospital for Sick Children
- Investigators
- Edgar Jaeggi, MD, Principal investigator, The Hospital for Sick Children, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02624765
- Sponsor's protocol ID
- 1000039945
- Status last verified
- May 2024
- First submitted
- 30 Nov 2015
- Last updated
- 22 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Not planned
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- FAST RCT: Prospective Randomized Clinical Trial of Fetal Atrial Flutter & Supraventricular Tachycardia Therapy
- ClinicalTrials.gov ID
- NCT02624765
- Acronym / sponsor ID
- 1000039945
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- Edgar JaeggiUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- Feb 2016 (actual)
- Primary completion
- 31 Mar 2024 (actual)
- Study completion
- 31 Mar 2024 (actual)
- First posted
- 8 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| RCT A (1st arm): AF without hydrops | Active comparator | Drug: Digoxin (monotherapy)Atrial Flutter (AF) without hydrops: Treatment with Digoxin as monotherapy. |
| RCT A (2nd arm): AF without hydrops | Active comparator | Drug: Sotalol (monotherapy)Atrial Flutter (AF) without hydrops: Treatment with Sotalol as monotherapy. |
| RCT B (1st arm): SVT without hydrops | Active comparator | Drug: Digoxin (monotherapy)Supraventricular Tachycardia (SVT) without hydrops: Treatment with Digoxin as monotherapy. |
| RCT B (2nd arm): SVT without hydrops | Active comparator | Drug: Flecainide (monotherapy)Supraventricular Tachycardia (SVT) without hydrops: Treatment with Flecainide as monotherapy. |
| RCT C (1st arm): SVT with hydrops | Active comparator | Drug: Digoxin (dual therapy), Drug: Sotalol (dual therapy)Supraventricular Tachycardia (SVT) with hydrops: Treatment with Digoxin and Sotalol. |
| RCT C (2nd arm): SVT with hydrops | Active comparator | Drug: Digoxin (dual therapy), Drug: Flecainide (dual therapy)Supraventricular Tachycardia (SVT) with hydrops: Treatment with Digoxin and Flecainide. |
Who may qualify
- Ages
- 16 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (14 listed)
- 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:
- Gestational age > 12 0/7 weeks and <36 0/7 weeks at time of enrollment
- Untreated tachycardia at time of enrollment
Key exclusion criteria (10 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Drug | RCT A (1st arm): AF without hydrops, RCT B (1st arm): SVT without hydrops |
| Sotalol (monotherapy)Oral dose: 80 mg TID or 120 mg BID (240 mg/day) | Drug | RCT A (2nd arm): AF without hydrops |
| Flecainide (monotherapy)Oral dose: 100 mg TID (300 mg/day) | Drug | RCT B (2nd arm): SVT without hydrops |
| 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 | Drug | RCT C (1st arm): SVT with hydrops, RCT C (2nd arm): SVT with hydrops |
| Sotalol (dual therapy)Oral dose: 160 mg BID (320 mg/day) | Drug | RCT C (1st arm): SVT with hydrops |
| Flecainide (dual therapy)Oral dose:100 mg TID (300 mg/day) | Drug | RCT C (2nd arm): SVT with hydrops |
Primary outcome
Proportion of live-born children with a delivery at term and a normal cardiac rhythm
Time frame: Term: 37 0/7 to 41 6/7 weeks
Term delivery (≥37 0/7 weeks gestation) with a normal cardiac rhythm (ECG).
7 secondary outcomes
Proportion of patients with cardioversion over time
Time frame: 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
Time frame: 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
Time frame: From date of randomization to 30 days of life
Average gestational age at birth
Time frame: At birth
Birth weight z-scores
Time frame: At birth
Total days of treatment related maternal and neonatal hospitalizations
Time frame: From date of randomization to 30 days of life
Maternal prevalence of adverse events and outcome
Time frame: From date of randomization to 30 days of life
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2024.
- Individual participant dataSharing planned: No. Not planned
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edgar Jaeggi, MD principal investigator
The Hospital for Sick Children, Toronto
22 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Digoxin (monotherapy), Sotalol (monotherapy) and Flecainide (monotherapy) in people with Fetal Atrial Flutter Without Hydrops and Fetal Supraventricular Tachycardia Without Hydrops, run by Edgar Jaeggi at 22 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States, Canada, Netherlands, Australia, Germany and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of live-born children with a delivery at term and a normal cardiac rhythm (time frame: Term: 37 0/7 to 41 6/7 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2024.