Prenatal Steroids for Treatment of Congenital Cystic Adenomatoid Malformations (CCAM) (CCAM Steroids)

Investigation of Prenatal Steroids for Treatment of Prenatally Diagnosed CCAMs

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

Study Overview

• Status: Terminated
• Conditions: Congenital Cystic Adenomatoid Malformation
• Intervention / Treatment: Drug: Betamethasone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco Fetal Treatment Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229-3039
      • Cincinnati Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Study Group; STEROID: Betamethasone; 12 mg intramuscularly x 2 doses 24 hours apart	Drug: Betamethasone; 12 mg intramuscularly x 2 doses 24 hours apart
Placebo Comparator: Placebo Group; PLACEBO: IM x 2 doses 24 hours apart	Drug: Placebo; PLACEBO: IM x 2 doses 24 hours apart

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Hydrops Fetalis	Delivery, up to approximately 20 weeks post-enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of CCAM Size in Mid-trimester Fetuses (Study/Administration vs Control/Placebo)		Baseline, Delivery (up to approximately 20 weeks post-enrollment)
Survival at One-month Between Study and Control Groups.	Status of neonate survival 30 days after delivery	30 days after delivery (up to approximately 24 weeks post-enrollment)

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Children's Hospital of Philadelphia; Children's Hospital Medical Center, Cincinnati
• Investigators: Principal Investigator: Timothy M Crombleholme, MD, Children's Hospital of Cincinnati; Principal Investigator: Douglas Wilson, MD, Children's Hospital of Philadelphia

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Helpful Links

• Fetal Care Center of Cincinnati Children's Hospital
• Fetal Treatment Center at the University of California, San Francisco

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: April 30, 2008
• First Submitted That Met QC Criteria: May 1, 2008
• First Posted (Estimate): May 2, 2008

Study Record Updates

• Last Update Posted (Estimate): March 30, 2015
• Last Update Submitted That Met QC Criteria: March 18, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: prenatal diagnosis; betamethasone; hydrops; prenatal steroids; congenital cystic adenomatoid malformation of the lung; prenatal intervention
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Respiratory System Abnormalities; Congenital Abnormalities; Cystic Adenomatoid Malformation of Lung, Congenital; Physiological Effects of Drugs; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Asthmatic Agents; Respiratory System Agents; Betamethasone
• Other Study ID Numbers: 10-03705