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

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00670956
• Collaborator: Children's Hospital Medical Center, Cincinnati (Other), Children's Hospital of Philadelphia (Other)
• Enrollment: 1
• Locations: 3
• Arms: 2
• Duration (Months): 41
• Patients Per Site: 0.3
• Patients Per Site Per Month: 0

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Congenital Cystic Adenomatoid Malformation	Drug: Betamethasone; Drug: Placebo	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Investigation of Prenatal Steroids for Treatment of Prenatally Diagnosed CCAMs
• Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Incidence of Hydrops Fetalis [Delivery, up to approximately 20 weeks post-enrollment]

Secondary Outcome Measures

1. Comparison of CCAM Size in Mid-trimester Fetuses (Study/Administration vs Control/Placebo) [Baseline, Delivery (up to approximately 20 weeks post-enrollment)]

2. Survival at One-month Between Study and Control Groups. [30 days after delivery (up to approximately 24 weeks post-enrollment)]

   Status of neonate survival 30 days after delivery

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Francisco Fetal Treatment Center	San Francisco	California	United States	94143
2	Cincinnati Children's Hospital	Cincinnati	Ohio	United States	45229-3039
3	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of California, San Francisco
• Children's Hospital Medical Center, Cincinnati
• Children's Hospital of Philadelphia

Investigators

• Principal Investigator: Timothy M Crombleholme, MD, Children's Hospital of Cincinnati
• Principal Investigator: Douglas Wilson, MD, Children's Hospital of Philadelphia
• Principal Investigator: Hanmin Lee, MD, University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

• Arca MJ, Teich S. Current controversies in perinatal care: fetal versus neonatal surgery. Clin Perinatol. 2004 Sep;31(3):629-48. Review.
• 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. Review.
• 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. Review.
• 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.
• Neilson JP. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Obstet Gynecol. 2007 Jan;109(1):189-90.
• Peltoniemi OM, Kari MA, Tammela O, Lehtonen L, Marttila R, Halmesmäki 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.
• 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. Review. Update in: Cochrane Database Syst Rev. 2017 Mar 21;3:CD004454.
• Schumacher A, Sidor J, Bühling 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. German.
• 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. Review.
• 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.
• 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.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT00670956
• Other Study ID Numbers: 10-03705
• First Posted: May 2, 2008
• Last Update Posted: Mar 30, 2015
• Last Verified: Mar 1, 2015

• Keywords provided by University of California, San Francisco: prenatal steroids; hydrops; congenital cystic adenomatoid malformation of the lung; prenatal intervention; betamethasone; prenatal diagnosis
• Additional relevant MeSH terms: Cystic Adenomatoid Malformation of Lung, Congenital; Congenital Abnormalities; Betamethasone

Study Results

Participant Flow

Recruitment Details	Only one participant was enrolled to the study before it was terminated; no participants were enrolled to the control arm

Arm/Group Title	Active Study Group
Arm/Group Description	STEROID: Betamethasone; 12 mg intramuscularly x 2 doses 24 hours apart Betamethasone: 12 mg intramuscularly x 2 doses 24 hours apart
Period Title: Overall Study
STARTED	1
COMPLETED	1
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Active Study Group
Arm/Group Description	STEROID: Betamethasone; 12 mg intramuscularly x 2 doses 24 hours apart Betamethasone: 12 mg intramuscularly x 2 doses 24 hours apart
Overall Participants	1
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	1 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 100%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	1 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Only one participant was enrolled to the study before it was terminated; no participants were enrolled to the control arm

Arm/Group Title	Active Study Group
Arm/Group Description	STEROID: Betamethasone; 12 mg intramuscularly x 2 doses 24 hours apart Betamethasone: 12 mg intramuscularly x 2 doses 24 hours apart
Measure Participants	1
Number [participants]	0 0%

2. Secondary Outcome

Title	Comparison of CCAM Size in Mid-trimester Fetuses (Study/Administration vs Control/Placebo)
Time Frame	Baseline, Delivery (up to approximately 20 weeks post-enrollment)

Outcome Measure Data

Analysis Population Description

Study was terminated without enrollment to control arm; therefore, no comparison was made

Arm/Group Title	Active Study Group
Arm/Group Description	STEROID: Betamethasone; 12 mg intramuscularly x 2 doses 24 hours apart Betamethasone: 12 mg intramuscularly x 2 doses 24 hours apart
Measure Participants	0

3. Secondary Outcome

Title	Survival at One-month Between Study and Control Groups.
Description	Status of neonate survival 30 days after delivery
Time Frame	30 days after delivery (up to approximately 24 weeks post-enrollment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Study Group
Arm/Group Description	STEROID: Betamethasone; 12 mg intramuscularly x 2 doses 24 hours apart Betamethasone: 12 mg intramuscularly x 2 doses 24 hours apart
Measure Participants	1
Number [participants]	1 100%

Adverse Events

Time Frame	30 days post-delivery (up to approximately 24 weeks)
Arm/Group Title	Active Study Group
Arm/Group Description	STEROID: Betamethasone; 12 mg intramuscularly x 2 doses 24 hours apart Betamethasone: 12 mg intramuscularly x 2 doses 24 hours apart
All Cause Mortality
	Active Study Group
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Active Study Group
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	Active Study Group
	Affected / at Risk (%)	# Events
Total	0/1 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.