Clinical trial NCT01736956: Fetal Intervention for Aortic Stenosis and Evolving Hypoplastic Left Heart Syndrome
Official title: Fetal Intervention for Aortic Stenosis and Evolving Hypoplastic Left Heart Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Aortic Stenosis
Hypoplastic Left Heart Syndrome
Keywords: aortic stenosis
hypoplastic left heart syndrome
fetal aortic valvuloplasty
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2012-11-29
Enrollment: 9
Sex: FEMALE
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: For fetuses with severe aortic stenosis, in utero balloon aortic valvuloplasty may improve fetal growth of left heart structures and thus improve potential for biventricular repair strategies after birth.

Detailed description: Fetal aortic stenosis is an anatomically simple birth defect in which there is partial blockage of the aortic valve, limiting blood flow out of the left side of the heart. If the blockage becomes severe in fetal life, the left heart structures may stop growing and the baby may be born with hypoplastic left heart syndrome (HLHS), a lethal condition without neonatal heart surgery or heart transplantation. Standard treatment for babies born with HLHS includes three major cardiac operations before the age of 6 years. Postnatal outcomes for HLHS are uncertain and vary with patient; however, the few adult survivors are currently suffering substantial medical problems, including a high incidence of neurologic problems. For fetuses with severe obstruction, fetal intervention may improve outcomes by increasing flow through the left heart, thus improving left heart function and encouraging continued growth of the left heart structures. If fetal intervention can preserve left heart function and growth, this should provide a better prognosis for the baby and allow for biventricular repair strategies after birth.

This research study is a prospective, non-randomized clinical trial of 30 patients that will assess the safety and efficacy of in utero percutaneous balloon dilation of fetal aortic valve with severe stenosis. This technique has been successfully used to perform postnatal aortic valve dilations for several decades, but has had limited application and study in utero.

Pregnant women carrying a fetus diagnosed with severe aortic stenosis will be referred to the University of California, San Francisco Fetal Treatment Center for evaluation, initial screening and counseling. If all fetal and maternal inclusion criteria are met, the balloon aortic valvuloplasty operation will be offered to the pregnant woman. Patients who do not meet study eligibility or decline prenatal intervention will be offered the option to enroll as a study control.

Eligibility criteria: Inclusion Criteria:

* Pregnant woman carrying a fetus with normal cardiac segmental anatomy and severe aortic stenosis as defined by:

  * Dysplastic/stenotic aortic valve with forward flow, with or without gradient, and no significant insufficiency
  * If mitral insufficiency (incomplete closure of the mitral valve)is present, left ventricle systolic pressure calculation must be ≥ a normal systemic blood pressure (BP) for gestational age
  * Retrograde aortic arch flow
  * Left to right atrial shunting
  * Left ventricle length no less than 90% the length of the right ventricle
* Maternal age ≥ 16 years of age;
* Gestational age: 17 0/7-30 6/7 weeks' gestation as determined by clinical information and evaluation of first ultrasound. (Aortic valve dilation procedure cannot be performed until 18 0/7 weeks);
* Normal karyotype with written confirmation of results. Results by fluorescence in situ hybridization (FISH) for aneuploidy will be acceptable if the patient is at 24 weeks or more; non-invasive testing is acceptable (maternal serum testing for cell-free fetal DNA, currently commercially available).
* Singleton pregnancy;
* Able to travel to study site for study evaluation, procedures, and visits;
* Support person to travel and stay with patient (support person will be required to sign the support person consent form);
* Has received pre-authorization for insurance for fetal intervention or has the ability to self-pay for study treatment

Exclusion Criteria:

* Failure to meet all inclusion criteria;
* Multi-fetal pregnancy;
* Insulin dependent pregestational diabetes;
* Fetal anomaly not related to aortic stenosis. A detailed fetal anatomic ultrasound will be conducted before consideration for the study and if the finding is abnormal, the patient will be excluded;
* Current or planned cerclage or documented history of incompetent cervix;
* Placenta previa or placental abruption;
* Short cervix (\< 20mm) measured by cervical ultrasound;
* Previous spontaneous delivery prior to 37 weeks of a singleton pregnancy. If the study candidate had intact membranes and was induced, this is not considered spontaneous. Stillbirths prior to 37 weeks are not exclusionary.
* Obesity as defined by body mass index of 35 or greater;
* Maternal-fetal Rh isoimmunization, Kell sensitization or a history of neonatal alloimmune thrombocytopenia;
* Positive maternal HIV status. This is due to the increased risk of transmission to the fetus during the maternal-fetal procedure. If the patient's HIV status is unknown, the patient must be tested and found to have negative results before she can be entered into the fetal treatment group;
* Known Hepatitis C positivity. If the patient's Hepatitis C status is unknown, she does not need to be screened;
* Other maternal medical condition which is a contraindication to surgery or general anesthesia, such as asthma, cardiac disease, the refusal of a blood transfusion, or a previous hysterotomy in the active segment of the uterus;
* Patient does not have a support person (e.g., husband, partner, mother), or that support person is unwilling to sign the support person consent form;
* Inability to comply with the travel and follow-up requirements of the study;
* Patient does not meet other psychosocial criteria to handle the implications of the study;
* Participation in another intervention study that influences maternal and fetal morbidity and mortality;
* Maternal hypertension which would increase the risk of preeclampsia or preterm delivery (including, but not limited to: uncontrolled hypertension, chronic hypertension with end organ damage and new onset hypertension in current pregnancy).

Primary outcomes:
measure: Improved fetal mitral valve and left ventricular growth
timeFrame: Monthly until birth, and after birth until three years of age
Secondary outcomes:
measure: Neonatal survival at 365 days of life
timeFrame: 365 days after birth
Other outcomes:
measure: Neurodevelopmental and functional status
timeFrame: Birth to 30 months
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco Fetal Treatment Center
state: California
Study officials:
affiliation: University of California, San Francisco
name: Anita Moon-Grady, MD
role: PRINCIPAL_INVESTIGATOR
References: