Clinical Trial: Preventive IVIG Therapy for Congenital Heart Block

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Preventive IVIG Therapy for Congenital Heart Block (The PITCH Study)

Brief Summary: Neonatal lupus (NL) is the name given to a group of conditions that can affect the babies of mothers who have certain autoantibodies against components of the body's cells that are called SSA/Ro and SSB/La. NL can appear as a temporary rash that usually goes away by the time the baby is 6 months old, or very rarely an abnormal blood or liver condition that also improves with time - or it can cause permanent and often life-threatening damage to the fetal heart, known as congenital heart block (CHB). In women with anti-Ro/La antibodies who are pregnant for the first time, only about 2% of the babies will develop CHB. But for a woman who has already had a child with CHB or NL rash, the risk of CHB in her next pregnancy is nearly 20%. Unfortunately, once complete (third degree) heart block has been unequivocally identified in a fetus, it has never been reversed with any of the therapies that have been tried to date. Our previous studies strongly indicate that scarring of the conduction system (the heart's own natural "pacemaker"), a consequence of inflammation triggered by the mother's antibodies, damages or even destroys the cells that allow the heart to beat at a normal rhythm. Instead, the damaged heart beats extremely slowly, to an extent that is fatal to nearly 20% of affected babies (with most deaths occurring as fetal demises). Nearly all surviving children with CHB require permanent implantation of a pacemaker device. Because it is so difficult to treat or repair the damaged heart, a high-priority strategy is to try to prevent the inflammatory process before irreversible scarring can occur. The aim of this clinical-based proposal is to determine whether treating the pregnant mother with intravenous immune globulin (IVIG) will prevent the development of CHB.

Detailed Summary:

Perhaps the strongest clinical association with autoantibodies against SSA/Ro-SSB/La is the development of congenital heart block (CHB) in an offspring, an alarming prospect facing 2% of primigravid mothers with these antibodies. Recurrence rates approach 20%. Disease can progress rapidly, with advanced block and life-threatening cardiomyopathy observed less than 2 weeks from normal sinus rhythm. Once 3rd degree (complete) block is identified, reversal has never been achieved, despite dexamethasone. This makes biologic sense since the signature lesion is fibrosis of the atrioventricular node. Thus, strategies aimed at preventing disease assume high priority. Although disease expression in the fetus requires additional factors to amplify the cascade to fibrosis, maternal anti-Ro/La antibodies are necessary. Accordingly, eliminating fetal exposure to these antibodies is a sound and important approach. Intravenous immune globulin (IVIG) is particularly exciting in its potential not only to lower maternal antibody levels (which is not accomplished with glucocorticoids or immunosuppression), but actually to influence effector mechanisms in the fetus itself. Aim 1 is a clinical trial to assess the efficacy of IVIG in preventing CHB. Proof of efficacy is challenging since CHB occurs in only 2% of first pregnancies of anti-Ro/La+ women. However, given the 10-fold higher risk of CHB in a pregnancy after the birth of child with neonatal lupus (NL), mothers with previous NL-affected children are the target population for study. Sample size calculations employ Simon's 2-stage optimal design. Based on a 2-sided significance level of 0.05, a power of 90% to show reduction of risk to 5% given the prediction that 18% of untreated subjects will get some degree of CHB, Stage 1 will enroll 19 women who have had a previous child with CHB or NL rash, to receive IVIG (400 mg/kg IVIG every 3 weeks for a total of 5 treatments) from weeks 12 thr
Sponsor: New York University School of Medicine

Current Primary Outcome: 2nd or 3rd degree heart block [ Time Frame: 1 Day ]

Original Primary Outcome: 2nd or 3rd degree heart block

Current Secondary Outcome:

  • Prolonged PR interval (>0.150 sec) [ Time Frame: 1 Day ]
  • Sign of myocardial injury, w/o change in heart rate/rhythm [ Time Frame: 1 Day ]
  • Echocardiographic density consistent with EFE [ Time Frame: 1 Day ]
  • Fetal death [ Time Frame: 1 Day ]
  • Rash consistent w neonatal lupus [ Time Frame: 1 Day ]
  • Gestational age at birth [ Time Frame: 1 Day ]
  • Birth weight [ Time Frame: 1 Day ]
  • Abnormal fluid collection [ Time Frame: 1 Day ]


Original Secondary Outcome:

  • Prolonged PR interval (>0.150 sec)
  • Sign of myocardial injury, w/o change in heart rate/rhythm
  • Echocardiographic density consistent with EFE
  • Fetal death
  • Rash consistent w neonatal lupus
  • Gestational age at birth
  • Birth weight
  • Abnormal fluid collection


Information By: New York University School of Medicine

Dates:
Date Received: April 13, 2007
Date Started: April 2007
Date Completion:
Last Updated: March 15, 2017
Last Verified: March 2017