Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Canadian Institutes of Health Research (CIHR) | OTHER_GOV |
Not provided
Not provided
Not provided
Not provided
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).
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).
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| RCT A (1st arm): AF without hydrops | Active Comparator | Atrial Flutter (AF) without hydrops: Treatment with Digoxin as monotherapy. |
|
| RCT A (2nd arm): AF without hydrops | Active Comparator | Atrial Flutter (AF) without hydrops: Treatment with Sotalol as monotherapy. |
|
| RCT B (1st arm): SVT without hydrops | Active Comparator | Supraventricular Tachycardia (SVT) without hydrops: Treatment with Digoxin as monotherapy. |
|
| RCT B (2nd arm): SVT without hydrops | Active Comparator | Supraventricular Tachycardia (SVT) without hydrops: Treatment with Flecainide as monotherapy. |
|
| RCT C (1st arm): SVT with hydrops | Active Comparator | Supraventricular Tachycardia (SVT) with hydrops: Treatment with Digoxin and Sotalol. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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 |
Not provided
Inclusion Criteria:
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
Singleton Pregnancy
Healthy mother with ± normal pre-treatment cardiovascular findings:
Exclusion Criteria:
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:
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)
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Edgar Jaeggi, MD | The Hospital for Sick Children, Toronto | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Benioff Children's Hospital | San Francisco | California | 94158 | United States | ||
| Children's Hospital of Colorado |
Not planned
Not provided
Not provided
Not provided
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 7, 2017 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| RCT C (2nd arm): SVT with hydrops |
| Active Comparator |
Supraventricular Tachycardia (SVT) with hydrops: Treatment with Digoxin and Flecainide. |
|
| 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) |
|
| 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. | 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 | From date of randomization to 30 days of life |
| Average gestational age at birth | Mean of the gestational age at birth | 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 | At birth |
| Total days of treatment related maternal and neonatal hospitalizations | Average days of maternal and neonatal hospitalization related to SVA therapy | 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 | From date of randomization to 30 days of life |
| Aurora |
| Colorado |
| 80045 |
| United States |
| Children's National Health System | Washington D.C. | District of Columbia | 20010 | United States |
| Morgan Stanley Children's Hospital of New York-Presbyterian | New York | New York | 10032 | United States |
| Cohen Children's Medical Center | New York | New York | 269-01 | United States |
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
| Pediatrix Medical Services, Inc, | Austin | Texas | 78722 | United States |
| Baylor College of Medicine | Houston | Texas | 77030 | United States |
| University of Utah | Salt Lake City | Utah | 84112 | United States |
| West Virginia University Research Corporation | Morgantown | West Virginia | 26506 | United States |
| Children's Hospital of Wisconsin | Milwaukee | Wisconsin | 53226 | 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 | V6H 3N1 | 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 |
| Sep 25, 2017 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D004077 | Digoxin |
| D013015 | Sotalol |
| D005424 | Flecainide |
| ID | Term |
|---|---|
| D004071 | Digitalis Glycosides |
| D002298 | Cardenolides |
| D002301 | Cardiac Glycosides |
| D002297 | Cardanolides |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D000588 | Amines |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided