Clinical trial NCT00670956: Prenatal Steroids for Treatment of Congenital Cystic Adenomatoid Malformations (CCAM)
Official title: Investigation of Prenatal Steroids for Treatment of Prenatally Diagnosed CCAMs
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Congenital Cystic Adenomatoid Malformation
Keywords: prenatal steroids
hydrops
congenital cystic adenomatoid malformation of the lung
prenatal intervention
betamethasone
prenatal diagnosis
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Children's Hospital Medical Center, Cincinnati
name: Children's Hospital of Philadelphia
First posted: 2008-05-02
Enrollment: 1
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Congenital cystic adenomatoid malformations (CCAMs) are theorized to be growing immature lung tissue. Administration of maternal steroids in the mid-trimester may stop the growth or decrease the size of the CCAM, thus increasing normal lung tissue and improving survival in fetuses with large CCAMs. This is a prospective, blinded, randomized trial comparing administration of a single course of antenatal steroids (Betamethasone) to control (i.e., placebo). The primary outcome variable will be incidence of hydrops. One month postnatal survival and relative size of the CCAM as determined by CCAM volume:head circumference ratio (CVR) between treatment/no treatment groups will be secondary outcome variables. Change in size of CCAM will be serially followed for both groups with individual growth curves being plotted prenatally and these will be compared with pathology weigh and volume to evaluate treatment effect. Other prenatal data collected will include: incidence of polyhydramnios, incidence of premature rupture of membranes, incidence of material complications. We will also compare mode of delivery, postnatal respiratory compromise, need for resection in the first week of life, and occurrence of complications during newborn administration


Eligibility criteria: Inclusion Criteria:

* GA \< 26 weeks
* Maternal age \> 18 years of age
* Singleton pregnancy
* Normal chromosomes
* CCAM volume to head circumference ratio (CVR) \> 1.4
* No maternal medical/surgical contraindications
* No evidence of hydrops
* Not previously randomization

Exclusion Criteria:

* Maternal diabetes or use of insulin
* Preterm labor
* Multiple congenital anomalies with CCAM
* Chromosomal anomaly with CCAM
* Multiple gestation pregnancy with CCAM
* Not willing to be randomized
* Unable or unwilling to return to UCSF for second dose of drug or placebo
* CVR \< 1.4

Primary outcomes:
measure: Incidence of Hydrops Fetalis
timeFrame: Delivery, up to approximately 20 weeks post-enrollment
Secondary outcomes:
measure: Comparison of CCAM Size in Mid-trimester Fetuses (Study/Administration vs Control/Placebo)
timeFrame: Baseline, Delivery (up to approximately 20 weeks post-enrollment)
measure: Survival at One-month Between Study and Control Groups.
timeFrame: 30 days after delivery (up to approximately 24 weeks post-enrollment)
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco Fetal Treatment Center
state: California
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Cincinnati
name: Timothy M Crombleholme, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital of Philadelphia
name: Douglas Wilson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Hanmin Lee, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vu L, Tsao K, Lee H, Nobuhara K, Farmer D, Harrison M, Goldstein RB. Characteristics of congenital cystic adenomatoid malformations associated with nonimmune hydrops and outcome. J Pediatr Surg. 2007 Aug;42(8):1351-6. doi: 10.1016/j.jpedsurg.2007.03.039.
citation: Schumacher A, Sidor J, Buhling KJ. [Continuous glucose monitoring using the glucose sensor CGMS in metabolically normal pregnant women during betamethasone therapy for fetal respiratory distress syndrome]. Z Geburtshilfe Neonatol. 2006 Oct;210(5):184-90. doi: 10.1055/s-2006-951743. German.
citation: Peltoniemi OM, Kari MA, Tammela O, Lehtonen L, Marttila R, Halmesmaki E, Jouppila P, Hallman M; Repeat Antenatal Betamethasone Study Group. Randomized trial of a single repeat dose of prenatal betamethasone treatment in imminent preterm birth. Pediatrics. 2007 Feb;119(2):290-8. doi: 10.1542/peds.2006-1549.
citation: Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2006 Jul 19;(3):CD004454. doi: 10.1002/14651858.CD004454.pub2.
citation: Neilson JP. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Obstet Gynecol. 2007 Jan;109(1):189-90. doi: 10.1097/01.aog.0000251610.51286.b1. No abstract available.
citation: Tsao K, Hawgood S, Vu L, Hirose S, Sydorak R, Albanese CT, Farmer DL, Harrison MR, Lee H. Resolution of hydrops fetalis in congenital cystic adenomatoid malformation after prenatal steroid therapy. J Pediatr Surg. 2003 Mar;38(3):508-10. doi: 10.1053/jpsu.2003.50089.
citation: Arca MJ, Teich S. Current controversies in perinatal care: fetal versus neonatal surgery. Clin Perinatol. 2004 Sep;31(3):629-48. doi: 10.1016/j.clp.2004.03.016.
citation: Wilson RD, Baxter JK, Johnson MP, King M, Kasperski S, Crombleholme TM, Flake AW, Hedrick HL, Howell LJ, Adzick NS. Thoracoamniotic shunts: fetal treatment of pleural effusions and congenital cystic adenomatoid malformations. Fetal Diagn Ther. 2004 Sep-Oct;19(5):413-20. doi: 10.1159/000078994.
citation: Knox EM, Kilby MD, Martin WL, Khan KS. In-utero pulmonary drainage in the management of primary hydrothorax and congenital cystic lung lesion: a systematic review. Ultrasound Obstet Gynecol. 2006 Oct;28(5):726-34. doi: 10.1002/uog.3812.
citation: Davenport M, Warne SA, Cacciaguerra S, Patel S, Greenough A, Nicolaides K. Current outcome of antenally diagnosed cystic lung disease. J Pediatr Surg. 2004 Apr;39(4):549-56. doi: 10.1016/j.jpedsurg.2003.12.021.
citation: Miller JA, Corteville JE, Langer JC. Congenital cystic adenomatoid malformation in the fetus: natural history and predictors of outcome. J Pediatr Surg. 1996 Jun;31(6):805-8. doi: 10.1016/s0022-3468(96)90138-4.