Dexamethasone + IVIG for Fetal AV Block

Recruiting at 40 trial locations

Overseen By Mala Masson

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: NYU Langone Health

Must be taking: Dexamethasone, IVIG

Must not be taking: Fluorinated steroids

Disqualifiers: Multi-fetal pregnancy, Allergic reactions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: Immediate upon detection

1300 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial involves pregnant women using a home device to monitor their baby's heart. If they detect any heart issues, they get a quick follow-up test at the hospital. The goal is to catch and treat heart issues early before they become serious.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking more than 20 mg of prednisone daily or any dose of fluorinated steroids.

What data supports the effectiveness of the drug Dexamethasone + IVIG for Fetal AV Block?

Research shows that dexamethasone, a drug with anti-inflammatory properties, can enhance the effectiveness of other treatments, such as prolonging the duration of pain relief when combined with local anesthetics. Additionally, intravenous gamma-globulin (IVIG) has been used to prevent complications in other fetal conditions, suggesting potential benefits when combined with dexamethasone. ^{1 2 3 4 5}

Is the combination of Dexamethasone and IVIG generally safe for humans?

In a study on Kawasaki disease, the combination of Dexamethasone and IVIG was used without any serious side effects reported. Additionally, IVIG is known to have dose-related side effects, but these are generally manageable. ^{2 3 6 7 8}

How is the drug Dexamethasone + IVIG unique for treating fetal AV block?

The combination of Dexamethasone and IVIG for treating fetal AV block is unique because it combines a steroid (Dexamethasone) known for reducing inflammation and immune responses with IVIG, which provides antibodies to help modulate the immune system. This dual approach may offer a novel way to manage the condition, as there are no standard treatments specifically for fetal AV block. ^{1 2 3 4 9}

Research Team

Jill Buyon, MD

Principal Investigator

NYU Langone Health

Bettina Cuneo, MD

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

This trial is for pregnant women over 18 with high levels of anti-Ro antibodies, which are linked to fetal heart block. They must be able to monitor the baby's heart rate at home, send audio texts, live within a 6-hour drive of the cardiology site, and take oral medication. It excludes those with multi-fetal pregnancies or known allergies to the study drugs.

Inclusion Criteria

I live within a 6-hour drive of the pediatric cardiology site.

I can have my baby's heart rate and rhythm checked with a Doppler outside of the hospital.

You have a high level of anti-Ro 52 or 60 antibodies in your blood.

Exclusion Criteria

I am not taking more than 20 mg of prednisone or any dose of fluorinated steroids currently.

I am a woman currently incarcerated.

The fetus already has a heart condition in the current pregnancy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Surveillance

Mothers perform fetal heart rate and rhythm monitoring (FHRM) 3 times daily and undergo weekly echocardiograms to detect 2° AVB.

up to 25 weeks

3 daily self-monitoring sessions, weekly in-person visits

Treatment

Rapid treatment of 2° AVB identified by FHRM and confirmed by echocardiogram, aiming to reverse 2° AVB before it becomes permanent.

Immediate upon detection

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of AV interval and extra-nodal cardiac disease.

up to 1 year post-birth

Regular follow-up visits

Treatment Details

Interventions

• Dexamethasone
• IVIG

Trial Overview The STOP BLOQ trial tests if early detection and treatment can prevent severe fetal atrioventricular block in babies whose mothers have specific autoantibodies. It involves risk assessment, home monitoring by mothers, and rapid treatment with Dexamethasone or IVIG upon detecting abnormalities.

Participant Groups

Group I: Mothers with Fetuses Who Have 2° AVB or AV interval > 170ms Experimental Treatment 2 Interventions

Dexamethasone is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases
• Immune system disorders

Approved in United States as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders
• Neoplastic diseases
• Nervous system disorders

Approved in Canada as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases

Approved in Japan as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

Findings from Research

In a study involving 150 patients undergoing upper limb surgery, perineural (PN) dexamethasone provided significantly longer durations of motor block (15.7 hours) and sensory block (16.8 hours) compared to intravenous (IV) dexamethasone (12.9 hours and 13.9 hours, respectively).

Both methods showed similar technical execution and success rates, but PN dexamethasone also extended postoperative analgesia duration (22.1 hours vs. 18.6 hours for IV), indicating it may be a more effective option for pain management in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multicenter Randomized Comparison Between Intravenous and Perineural Dexamethasone for Ultrasound-Guided Infraclavicular Block. Leurcharusmee, P., Aliste, J., Van Zundert, TC., et al.[2019]

Intravenous gamma-globulin treatment effectively increased platelet counts in thrombocytopenic fetuses, with a mean increase of 69,000/microliters from the first fetal blood sampling to birth, and no cases of intracranial hemorrhage were reported.

Dexamethasone did not enhance the effectiveness of intravenous gamma-globulin, but a 'salvage' treatment with prednisone improved platelet counts in 50% of nonresponders, indicating that gamma-globulin is a suitable first-line treatment for severe alloimmune thrombocytopenia in fetuses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antenatal management of alloimmune thrombocytopenia with intravenous gamma-globulin: a randomized trial of the addition of low-dose steroid to intravenous gamma-globulin. Bussel, JB., Berkowitz, RL., Lynch, L., et al.[2019]

In a study of 3600 very low birth weight infants, betamethasone was found to significantly reduce the risk of neonatal death and showed trends towards lower risks for other serious conditions compared to dexamethasone.

Dexamethasone was associated with a higher risk of neonatal death compared to betamethasone, suggesting that betamethasone may be the safer option for preventing adverse neonatal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse neonatal outcomes associated with antenatal dexamethasone versus antenatal betamethasone. Lee, BH., Stoll, BJ., McDonald, SA., et al.[2022]

Fetal intravenous treatment with low doses of dexamethasone significantly increased mean arterial blood pressure and altered vascular resistance in sheep fetuses, indicating a notable impact on cardiovascular function.

The effects of dexamethasone on fetal cardiovascular and endocrine responses varied over time, with some changes persisting or enhancing after treatment cessation, suggesting complex regulatory mechanisms at play.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of low dose dexamethasone treatment on basal cardiovascular and endocrine function in fetal sheep during late gestation. Fletcher, AJ., McGarrigle, HH., Edwards, CM., et al.[2019]

In a study of 42 patients undergoing caesarean sections, adding dexamethasone to levobupivacaine significantly prolonged the time before the first analgesic dose was needed, indicating enhanced pain relief.

Patients receiving dexamethasone reported lower pain scores and required significantly less additional tramadol for pain management compared to those receiving levobupivacaine alone, suggesting that dexamethasone improves the efficacy of local anaesthetic blocks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone added to levobupivacaine in ultrasound-guided tranversus abdominis plain block increased the duration of postoperative analgesia after caesarean section: a randomized, double blind, controlled trial. Akkaya, A., Yildiz, I., Tekelioglu, UY., et al.[2022]

The combination of intravenous immune globulin (IVIG) and dexamethasone (DEX) for treating Kawasaki disease was found to be safe and may help reduce systemic inflammation, as indicated by lower C-reactive protein levels compared to the control group.

Patients receiving the DEX regimen experienced a shorter duration of fever after treatment, averaging 2.2 days compared to 2.8 days in the control group, suggesting a potential benefit in clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of intravenous immune globulin therapy combined with dexamethasone for the initial treatment of acute Kawasaki disease. Jibiki, T., Terai, M., Kurosaki, T., et al.[2018]

In a study of 58 children receiving intravenous immunoglobulin (IVIG) for immunodeficiency or immunomodulation, immediate adverse events occurred in 10.3% of infusions, while delayed adverse events were reported in 41.4% of children, highlighting the prevalence of delayed reactions.

The most common delayed adverse event was headache, affecting 24.1% of patients and occurring in 12.8% of infusions, indicating that healthcare providers should be aware of and monitor for these frequent delayed effects in children undergoing IVIG therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective study of the immediate and delayed adverse events following intravenous immunoglobulin infusions. Singh-Grewal, D., Kemp, A., Wong, M.[2022]

In a study of 109 pregnant women with fetal and neonatal alloimmune thrombocytopenia (FNAIT), both 0.5 g/kg and 1.0 g/kg weekly doses of intravenous immunoglobulins (IVIG) resulted in similar neonatal platelet counts at birth, indicating that lower dosing may be just as effective.

There was no significant difference in the incidence of severe thrombocytopenia between the two dosing groups, and importantly, no cases of intracranial hemorrhage occurred, suggesting that both dosing regimens are safe for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lower-dose intravenous immunoglobulins for the treatment of fetal and neonatal alloimmune thrombocytopenia: a cohort study. Kamphuis, M., Paridaans, N., Winkelhorst, D., et al.[2018]

In a randomized control trial involving 48 preterm mothers, two regimens of dexamethasone were compared, showing that both regimens were equally effective in reducing the incidence of respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC), and intra-ventricular hemorrhage (IVH) in their newborns.

While group A (6mg in 4 doses) had fewer cases of RDS compared to group B (2 doses), the differences were not statistically significant, indicating that both dosing strategies are similarly effective in preventing neonatal complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of two regimens of dexamethasone for Management of preterm labour: pilot study. Rasool, A., Farooq, U., Nazir, QU., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

A Multicenter Randomized Comparison Between Intravenous and Perineural Dexamethasone for Ultrasound-Guided Infraclavicular Block. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Antenatal management of alloimmune thrombocytopenia with intravenous gamma-globulin: a randomized trial of the addition of low-dose steroid to intravenous gamma-globulin. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Adverse neonatal outcomes associated with antenatal dexamethasone versus antenatal betamethasone. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Effects of low dose dexamethasone treatment on basal cardiovascular and endocrine function in fetal sheep during late gestation. [2019]

5. Italy pubmed.ncbi.nlm.nih.gov

Dexamethasone added to levobupivacaine in ultrasound-guided tranversus abdominis plain block increased the duration of postoperative analgesia after caesarean section: a randomized, double blind, controlled trial. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Efficacy of intravenous immune globulin therapy combined with dexamethasone for the initial treatment of acute Kawasaki disease. [2018]

7. England pubmed.ncbi.nlm.nih.gov

A prospective study of the immediate and delayed adverse events following intravenous immunoglobulin infusions. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Lower-dose intravenous immunoglobulins for the treatment of fetal and neonatal alloimmune thrombocytopenia: a cohort study. [2018]

9. Pakistan pubmed.ncbi.nlm.nih.gov

Efficacy of two regimens of dexamethasone for Management of preterm labour: pilot study. [2019]