Moderate TOTAL Trial
Texas Children’s Fetal Center® in collaboration with Baylor College of Medicine is the first center in the United States to participate in the Moderate TOTAL trial. We are now enrolling pregnant women expecting a baby with moderate congenital diaphragmatic hernia (CDH).
What is CDH?
CDH is the abbreviation for Congenital Diaphragmatic Hernia. 'Congenital' means born with, 'Diaphragm' is the breathing muscle that separates the chest area from the abdomen, and 'Hernia' is a general term to describe the protrusion of an organ into a space where it is not meant to be.
CDH is a rare birth defect of the diaphragm that occurs very early in gestation. As a result of improper joining of the structures that form the diaphragm, a hole, or defect in the diaphragm, occurs. Consequently, intestines and other organs in the abdomen can move through the hole into the chest and press on the developing lungs. This prevents the lungs from growing and developing normally. CDH is classified as mild, moderate or severe based on several criteria including but not limited to the size of the defect (hole), herniation of the liver into the chest (or not), and the size or volume of the lungs. Maternal Fetal Medicine doctors need to run a variety of tests to be able to determine the severity of each case.
About the TOTAL Trial
As part of the clinical research study approved by the U.S. Food and Drug Administration (FDA), Texas Children’s Hospital and Baylor College of Medicine are offering to pregnant women expecting a baby with a diaphragm hernia of moderate severity the opportunity to participate in a clinical trial called the “TOTAL trial.”
The TOTAL Trial is an international, multicenter, non-blinded, randomized controlled trial in fetuses with isolated moderate CDH. A multicenter trial is a clinical trial that is being conducted in more than one institution. The TOTAL trial was initiated in Europe and Texas Children’s Hospital is the first site in the United States to join this study. A non-blinded study means that both the researchers and the participants (patients) know what kind of treatment each patient is assigned to. A randomized controlled trial is when the patient is randomly allocated (by chance only) to a specific group.
This trial will test whether temporary fetal endoscopic tracheal occlusion (FETO) rather than expectant management during pregnancy increases survival at discharge and decreases the need for oxygen at 6 months. There will be two groups of patients. One will receive standardized postnatal care (Expectant Group), and the other will receive the prenatal intervention (FETO Group).
Whether prenatal tracheal occlusion with a balloon truly improves outcomes in babies with moderate pulmonary hypoplasia (CDH) remains uncertain as the FETO procedure has so far only been offered to mothers with a baby that has severe CDH with extremely small lungs (severe pulmonary hypoplasia).
What is Fetoscopic Endoluminal Tracheal Occlusion (FETO)?
FETO is an experimental procedure that involves placing a small latex balloon in the trachea (windpipe) of the unborn baby. The expectation is that by blocking the baby’s airway the fluids that are normally produced by her lungs will remain inside the lungs, increasing the pressure, allowing opportunity for them to grow. The balloon will be removed a few weeks after the placement, before the delivery date.
How can I be enrolled in the trial?
Before determining the best course of treatment for your baby, you will need to undergo a standard prenatal evaluation at Texas Children’s Hospital to find out if you are a candidate for this research study. Your evaluation will include:
- Medical history and physical exam
- Obstetric ultrasound (US)
- Fetal echocardiogram
- Fetal magnetic resonance imaging (MRI)
- Psychosocial evaluation
- Meet inclusion criteria
If participation is an option, you and your baby’s father will be asked to consent for inclusion in the trial. Only after the consent form is signed and when all criteria are met, you will be officially entered into the study. Patients will be randomized by the research team via a website into one of two groups, “FETO” or “Expectant.”
What if I’m enrolled into the study?
Once entered into the study, if you are randomized to the Standard of care group you will not undergo any surgical procedures during your pregnancy but you will agree to be monitored during your pregnancy and to monitoring of your baby after birth. If you are allocated into the FETO group your unborn baby will undergo two procedures, the first will be to place the balloon in the baby’s airway and the second will be to remove the balloon. Independent of the arm to which you are allocated, your baby will still need to undergo surgery to repair the hole in the diaphragm after delivery.
What if I’m not happy with my randomization allocation?
Patients won’t be able to choose to which group they’re assigned. As part of the inclusion criteria, you must agree to accept randomization results. As a research participant, you may change your mind and decide to withdraw from the study at any time. However, if you withdraw from the study you won’t be able to re-enroll at any other participating FETO center. If you decide not to take part in this study, your standard of care will not be affected, normal procedures will be followed.
Cost and Payments
You and your insurance company will be responsible for payment of items and/or services considered to be routine care for the treatment or management of your medical condition. You will not be asked to pay any costs related to this research. You will be responsible for your travel expenses. If you need assistance finding and paying for a place to stay in Houston, a social worker is available during your evaluation to discuss options.
How to refer a patient
To refer a patient, please
- Call our referral line 1-877-338-2579
- Fill out our online form
- Fill out our print referral form and fax to 832-825-9403
To discuss any questions you may have, please call the Texas Children’s Fetal Center at (832) 822-2229 and our team will connect you to the appropriate nurse coordinator. You may also email us at FetalCenter@texaschildrens.org.
Texas Children’s Fetal Center®
Pavilion for Women
6651 Main Street, 4th floor
Houston, TX 77030
Phone: (832) 822-2229
Fax: (832) 825-9403
Both the fetus and the mother will need to meet the below inclusion criteria in order to participate in the trial. Exclusion criteria is listed below as well for consideration.
Inclusion criteria for the fetus:
- Left-sided diaphragmatic hernia.
- Presenting at the latest at 31 weeks plus 5 days (intervention at the latest on 31 weeks plus 6 days).
Predicted moderate pulmonary hypoplasia, determined by the US measurement (O/E LHR), ideally between 26 and 31 weeks, at the latest the day before occlusion.
- O/E LHR 25-34.9% (included) irrespective of the liver position, or
- O/E LHR 35-44.9% (included) with intrathoracic herniation of the liver
Inclusion criteria for the mother:
- Pregnant woman - maternal age 18 years or older and capable of consenting for their own participation in this study.
- Singleton pregnancy.
- Anatomically and chromosomally normal fetus (normal amniocentesis).
- Gestation at randomization prior to 31 weeks plus 5 days or so that occlusion is done at the latest on 31 weeks plus 6 days.
- Estimated to have moderate pulmonary hypoplasia. (defined as in Fetus criteria above)
- Acceptance of randomization and the consequences for the further management during pregnancy and thereafter; includes the required observation following FETO surgery, which lasts approximately 4 weeks after balloon is in place.
- Agree to either remaining close to, or at the Texas Children’s Hospital FETO center, or being able to travel swiftly and within acceptable time interval (within 30 minutes) to the Texas Children’s Hospital FETO center until the balloon is removed.
- Provide written consent to participate.
Exclusion criteria for the fetus and mother:
- Maternal contraindication to fetoscopic surgery or severe medical condition in pregnancy that make fetal intervention risk full.
- Technical limitations precluding fetoscopic surgery, such as severe maternal obesity, uterine fibroids or potentially others, not anticipated at the time of writing this protocol.
- Preterm labor, cervix shortened (<15 mm at randomization) or uterine anomaly strongly predisposing to preterm labor, placenta previa.
- Patient age less than 18 years.
- Psychosocial ineligibility, precluding consent.
- Diaphragmatic hernia: right-sided or bilateral, major anomalies, isolated left-sided outside the O/E LHR limits for the inclusion criteria.
- Patient refusing randomization or to comply with return to FETO center during the time period the airways are occluded or for elective removal of the balloon.
- Patient allergic to latex.