Dexamethasone Treatment for Congenital Heart Block (CHB) in Newborns With Lupus

Myocardial Injury Clinical Trial

Official title:

Study of Dexamethasone in Neonatal Lupus Congenital Heart Block; PRIDE (PR Interval and Dexamethasone Evaluation) in Congenital Heart Block

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00007358
• Other study ID #: R01AR046265
• Secondary ID: R01AR046265NIAMS
• Status: Completed
• Phase: N/A
• First received: December 19, 2000
• Last updated: March 10, 2016
• Start date: October 2000
• Est. completion date: October 2008

Study information

• Verified date: March 2016
• Source: New York University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: October 2008
• Est. primary completion date: April 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 16 Years to 50 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrioventricular Nodal Dysfunction
• Congenital Heart Block
• Heart Block
• Myocardial Injury
• Neonatal Lupus

Intervention

Drug:
• Dexamethasone or other corticosteroid
Administered during the third trimester of pregnancy

Locations

Country	Name	City	State
United States	St. Barnabas Medical Center	Livingston	New Jersey
United States	Yale University Medical Center	New Haven	Connecticut
United States	Hospital for Joint Diseases	New York	New York
United States	New York University Medical Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
New York University School of Medicine	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Country where clinical trial is conducted

United States, 

References & Publications (13)

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.

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. — View Citation

Buyon JP, Clancy RM. Neonatal lupus syndromes. Curr Opin Rheumatol. 2003 Sep;15(5):535-41. Review. — View 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. Review. — View 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. — View 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. — View 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. — View 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. — View Citation

Friedman D, Duncanson Lj, Glickstein J, Buyon J. A review of congenital heart block. Images Paediatr Cardiol. 2003 Jul;5(3):36-48. — View 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. Circulatio — View 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. Review. — View 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. — View 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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neonatal ventricular heart rate		Measured over 5 months	Yes
Primary	Fractional shortening		Measured over 5 months	No
Primary	Abnormal fluid collection		Measured over 5 months	Yes
Secondary	Change in degree of heart block		Measured over 5 months	No
Secondary	Gestational age (weeks) at birth		Measured over 5 months	No
Secondary	Birth weight		Measured over 5 months	No
Secondary	Cardiothoracic ratio		Measured over 5 months	No
Secondary	EKG and echocardiogram		Measured over 5 months	No