Ignite Creation Date:
2024-05-05 @ 5:29 PM
Last Modification Date:
2024-10-26 @ 9:32 AM
Study NCT ID:
NCT00460928
Status:
COMPLETED
Last Update Posted:
2019-09-30
First Post:
2007-04-13
Brief Title:
Preventive IVIG Therapy for Congenital Heart Block
Sponsor:
NYU Langone Health
Organization:
NYU Langone Health
Study Overview
Official Title:
Preventive IVIG Therapy for Congenital Heart Block The PITCH Study
Status:
COMPLETED
Status Verified Date:
2019-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PITCH
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 bodys cells that are called SSARo and SSBLa 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-RoLa 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 hearts own natural pacemaker a consequence of inflammation triggered by the mothers 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 Description:
Perhaps the strongest clinical association with autoantibodies against SSARo-SSBLa 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-RoLa 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-RoLa 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 Simons 2-stage optimal design Based on a 2-sided significance level of 005 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 mgkg IVIG every 3 weeks for a total of 5 treatments from weeks 12 through 24 of gestation If fewer than 3 mothers have children with 2nd or 3rd degree block then an additional 35 mothers will be enrolled in Stage 2 total 54 subjects IVIG will be considered efficacious and worthy of further study if fewer than 6 of 54 subjects have a child with advanced CHB Secondary outcomes include 1st degree block myocardial injury absent conduction defects and isolated endocardial fibroelastosis as assessed by serial fetal echocardiograms and EKG at birth
Aim 2 will address a the effect of IVIG on antibody titer and subclass b genetic polymorphisms in Fc gamma receptor FcgR and platelet-activating factor acetylhydrolase and their potential association with response to IVIG c whether a decrease in anti-La antibodies positively correlates with the level of anti-La antiidiotypic antibodies d whether IVIG blocks expression of activation markers on human macrophages after challenge with opsonized apoptotic cardiocytes and whether this positively correlates with increased expression of the inhibitory Fc receptor FcgRIIb
In sum IVIG is a promising agent that may have effects at several levels of the pathologic cascade to antibody-mediated CHB
Aim 2 will address a the effect of IVIG on antibody titer and subclass b genetic polymorphisms in Fc gamma receptor FcgR and platelet-activating factor acetylhydrolase and their potential association with response to IVIG c whether a decrease in anti-La antibodies positively correlates with the level of anti-La antiidiotypic antibodies d whether IVIG blocks expression of activation markers on human macrophages after challenge with opsonized apoptotic cardiocytes and whether this positively correlates with increased expression of the inhibitory Fc receptor FcgRIIb
In sum IVIG is a promising agent that may have effects at several levels of the pathologic cascade to antibody-mediated CHB
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None