Fetal Atrial Flutter Without Hydrops, Fetal Supraventricular Tachycardia With Hydrops, Fetal Supraventricular Tachycardia Without Hydrops
Conditions
Keywords
RCT A: Fetal Atrial Flutter without Hydrops, RCT B: Fetal Supraventricular Tachycardia without Hydrops, RCT C: Fetal Supraventricular Tachycardia with Hydrops
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).
Interventions
DRUGDigoxin (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
DRUGSotalol (monotherapy)
Oral dose: 80 mg TID or 120 mg BID (240 mg/day)
Oral dose: 100 mg TID (300 mg/day)
DRUGDigoxin (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
DRUGSotalol (dual therapy)
Oral dose: 160 mg BID (320 mg/day)
DRUGFlecainide (dual therapy)
Oral dose:100 mg TID (300 mg/day)
Sponsors
Canadian Institutes of Health Research (CIHR)
Edgar Jaeggi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
16 Years to 50 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of live-born children with a delivery at term and a normal cardiac rhythm | Term: 37 0/7 to 41 6/7 weeks | Term delivery (≥37 0/7 weeks gestation) with a normal cardiac rhythm (ECG). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| Proportion of participants with arrhythmia-related death | From date of randomization to 30 days of life | Number of participants with arrhythmia-related death compared to other outcomes |
| Average gestational age at birth | At birth | Mean of the gestational age at birth |
| 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 | Number of participants with persistent tachycardia compared to number of participants with cardioversion to a normal rhythm over time |
| Total days of treatment related maternal and neonatal hospitalizations | From date of randomization to 30 days of life | Average days of maternal and neonatal hospitalization related to SVA therapy |
| Maternal prevalence of adverse events and outcome | From date of randomization to 30 days of life | Maternal prevalence of pregnancy/treatment-related AEs and outcomes |
| Birth weight z-scores | At birth | 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 |
Countries
Australia, Canada, Germany, Netherlands, United Kingdom, United States
Outcome results
None listed