Clinical trial NCT00007358: Dexamethasone Treatment for Congenital Heart Block (CHB) in Newborns With Lupus
Official title: Study of Dexamethasone in Neonatal Lupus Congenital Heart Block; PRIDE (PR Interval and Dexamethasone Evaluation) in Congenital Heart Block
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Congenital Heart Block
Neonatal Lupus
Atrioventricular Nodal Dysfunction
Myocardial Injury
Keywords: Dexamethasone
Anti-SSA/Ro antibodies
Anti-SSB/La antibodies
Ultrasound
Atrioventricular (AV) nodal dysfunction
Echocardiograms
Mothers
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
Collaborators: name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
First posted: 2000-12-18
Enrollment: 150
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: Some newborns are born with congenital heart block (CHB), a condition occurring in babies with neonatal lupus. The first part of the study will test the effectiveness of fluorinated steroids, including dexamethasone, in improving the heart function and general health of newborns who have auto-antibody-associated CHB. The second part of this study will use ultrasound and heart monitoring to observe high-risk pregnant women and their fetuses during the third trimester of pregnancy.

Detailed description: CHB is an abnormal condition in which the heart beats slowly. This is a disease that is strongly associated with maternal antibodies to SSA/Ro and SSB/La ribonucleoproteins. This study hopes to clarify the causes of CHB and develop appropriate treatments. The study has two parts.

The first part of the study will be prospective; it will determine if fluorinated steroids given to women prior to birth improves the heart function and well-being of their newborns. This part of the study will evaluate fetuses diagnosed in utero with CHB during the third trimester of pregnancy. Diagnosis of CHB must occur at least 6 weeks before the baby is born to allow for sufficient data collection. It will be the decision of the physician and the mother as to whether a steroid will be administered. Fetuses will be evaluated before delivery by electrocardiogram (ECG) to detect abnormal fluid collection and by ultrasound to monitor heartbeat. After birth, newborns will be assessed for overall pumping strength of the heart and for abnormal heartbeat. Blood will be drawn from the mother at the time of enrollment and during delivery. Visits will occur over a span of approximately 5 months.

The second part of this study will be observational; the purpose is to identify classic indicators of heartbeat dysfunction and heart injury in newborns with CHB. The goal of this part of the study is to better understand the stages of heart injury, the role of anti-Ro/La antibodies in CHB, and procedures that may reverse heart block. Mothers considered to be at high risk for having a child with CHB will undergo weekly ECGs from 16 weeks into their pregnancy until Week 24, then will have an ECG every other week from Week 24 through Week 34. There will be a total of 15 visits to conduct these ECGs. Blood will be drawn at the first ECG visit and during delivery. Visits will occur over a span of 4 months.

For both parts of the study, babies will undergo ECGs after delivery and at one year of age. Additional tests not related to the study may be ordered by the physician.

Eligibility criteria: Inclusion Criteria for Prospective Part of Trial:

* Mother must have anti-Ro and/or anti-La antibody
* Fetal bradyarrhythmia (slow, abnormal heart rhythm)

Exclusion Criteria for Prospective Part of Trial:

* Fetal heart abnormalities that may cause newborn CHB and could account for atrioventricular (AV) block

Inclusion Criteria for Observational Part of Trial:

* Mother must have anti-Ro and/or anti-La antibody
* Fetus must have documented normal heartbeat prior to the 16th week of pregnancy
* Fetus must have a structurally normal heart
* Mother must be enrolled during the 16th, 17th, or 18th week of pregnancy

Exclusion Criteria for Observational Part of Trial:

* Mother is taking more than 10 mg of prednisone per day

Primary outcomes:
measure: Neonatal ventricular heart rate
timeFrame: Measured over 5 months
measure: Fractional shortening
timeFrame: Measured over 5 months
measure: Abnormal fluid collection
timeFrame: Measured over 5 months
Secondary outcomes:
measure: Change in degree of heart block
timeFrame: Measured over 5 months
measure: Gestational age (weeks) at birth
timeFrame: Measured over 5 months
measure: Birth weight
timeFrame: Measured over 5 months
measure: Cardiothoracic ratio
timeFrame: Measured over 5 months
measure: EKG and echocardiogram
timeFrame: Measured over 5 months
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University Medical Center
state: Connecticut
city: Livingston
country: United States
facility: St. Barnabas Medical Center
state: New Jersey
city: New York
country: United States
facility: Hospital for Joint Diseases
state: New York
city: New York
country: United States
facility: New York University Medical Center
state: New York
Study officials:
affiliation: Hospital for Joint Diseases
name: Jill P. Buyon
role: PRINCIPAL_INVESTIGATOR
References:
citation: Saleeb S, Copel J, Friedman D, Buyon JP. Comparison of treatment with fluorinated glucocorticoids to the natural history of autoantibody-associated congenital heart block: retrospective review of the research registry for neonatal lupus. Arthritis Rheum. 1999 Nov;42(11):2335-45. doi: 10.1002/1529-0131(199911)42:113.0.CO;2-3.
citation: Glickstein JS, Buyon J, Friedman D. Pulsed Doppler echocardiographic assessment of the fetal PR interval. Am J Cardiol. 2000 Jul 15;86(2):236-9. doi: 10.1016/s0002-9149(00)00867-5. No abstract available.
citation: Buyon JP, Waltuck J, Kleinman C, Copel J. In utero identification and therapy of congenital heart block. Lupus. 1995 Apr;4(2):116-21. doi: 10.1177/096120339500400207.
citation: Copel JA, Buyon JP, Kleinman CS. Successful in utero therapy of fetal heart block. Am J Obstet Gynecol. 1995 Nov;173(5):1384-90. doi: 10.1016/0002-9378(95)90621-5.
citation: Askanase AD, Friedman DM, Copel J, Dische MR, Dubin A, Starc TJ, Katholi MC, Buyon JP. Spectrum and progression of conduction abnormalities in infants born to mothers with anti-SSA/Ro-SSB/La antibodies. Lupus. 2002;11(3):145-51. doi: 10.1191/0961203302lu173oa.
citation: Friedman DM, Rupel A, Glickstein J, Buyon JP. Congenital heart block in neonatal lupus: the pediatric cardiologist's perspective. Indian J Pediatr. 2002 Jun;69(6):517-22. doi: 10.1007/BF02722656.
citation: Friedman D, Buyon J, Kim M, Glickstein JS. Fetal cardiac function assessed by Doppler myocardial performance index (Tei Index). Ultrasound Obstet Gynecol. 2003 Jan;21(1):33-6. doi: 10.1002/uog.11.
citation: Askanase A, Friedman D, Glickstein J, Kim M, Buyon J. Potential Therapeutic window from normal heart rate (NHR) to advanced heart blcok and early detection of firts degree block by echocardiographic measurement of the mechanical PR interval. Arthritis Rheum. 2002; 46(suppl);5321.
citation: Buyon JP, Clancy RM. Neonatal lupus: review of proposed pathogenesis and clinical data from the US-based Research Registry for Neonatal Lupus. Autoimmunity. 2003 Feb;36(1):41-50. doi: 10.1080/0891693031000067340.
citation: Buyon JP, Clancy RM. Neonatal lupus syndromes. Curr Opin Rheumatol. 2003 Sep;15(5):535-41. doi: 10.1097/00002281-200309000-00003.
citation: Buyon JP, Hiebert R, Copel J, Craft J, Friedman D, Katholi M, Lee LA, Provost TT, Reichlin M, Rider L, Rupel A, Saleeb S, Weston WL, Skovron ML. Autoimmune-associated congenital heart block: demographics, mortality, morbidity and recurrence rates obtained from a national neonatal lupus registry. J Am Coll Cardiol. 1998 Jun;31(7):1658-66. doi: 10.1016/s0735-1097(98)00161-2.
citation: Friedman D, Duncanson Lj, Glickstein J, Buyon J. A review of congenital heart block. Images Paediatr Cardiol. 2003 Jul;5(3):36-48.
citation: Friedman DM, Kim MY, Copel JA, Davis C, Phoon CK, Glickstein JS, Buyon JP; PRIDE Investigators. Utility of cardiac monitoring in fetuses at risk for congenital heart block: the PR Interval and Dexamethasone Evaluation (PRIDE) prospective study. Circulation. 2008 Jan 29;117(4):485-93. doi: 10.1161/CIRCULATIONAHA.107.707661. Epub 2008 Jan 14.