NCT01379573: PATCH

Preventive Approach to Congenital Heart Block With Hydroxychloroquine

Completed Phase 2 Results posted Last updated 25 February 2021

What this trial tests

Phase 2 trial testing Hydroxychloroquine in Congenital Heart Block in 74 participants. Completed in 16 July 2020.

Timeline

1 January 2011

Primary endpoint
16 July 2020

16 July 2020

Quick facts

Lead sponsor	NYU Langone Health
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	prevention
Enrollment	74
Start date	1 January 2011
Primary completion	16 July 2020
Estimated completion	16 July 2020
Sites	1 location across United States

Drugs / interventions tested

• Hydroxychloroquine (HYDROXYCHLOROQUINE) — full drug profile →

Conditions studied

• Congenital Heart Block — all drugs for Congenital Heart Block →
• Neonatal Lupus — all drugs for Neonatal Lupus →
• Autoantibody-Associated Heart Block — all drugs for Autoantibody-Associated Heart Block →

Sponsor

NYU Langone Health — full company profile →

Who can join

Adults 18 to 45, female only, with Congenital Heart Block or Neonatal Lupus. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Recurrence of Advanced Heart Block Primary · After enrollment at 16-18 weeks gestation, then weekly until 26 weeks, biweekly to 34 weeks, at birth (approximately 9 months), and at one year follow up (approximately 21 months from enrollment)

Echocardiogram reveals 2nd or 3rd degree AV block

Group	Value	95% CI
Pregnant Women With Previous Child With Cardiac Neonatal Lupus	5

Prolonged PR Interval (>150msec) Secondary · After enrollment at 16-18 weeks gestation, then weekly until 26 weeks, biweekly to 34 weeks, at birth (approximately 9 months), and at one year follow up (approximately 21 months from enrollment)

EKG at birth must confirm 1st degree AV block. It is also possible that a fetus developing 1st degree block on study medication might have developed more advanced block in the absence of study medication.

Group	Value	95% CI
Pregnant Women With Previous Child With Cardiac Neonatal Lupus	0

Any Sign of Myocardial Injury, Without Change in Cardiac Rate or Rhythm Secondary · After enrollment at 16-18 weeks gestation, then weekly until 26 weeks, biweekly to 34 weeks, at birth (approximately 9 months), and at one year follow up (approximately 21 months from enrollment)

a) shortening fraction \<28% = 2 SD below normal mean or qualitatively reduced systolic function; b) cardio-thoracic ratio \>0.33; c) hydropic changes; d) moderate/severe tricuspid regurgitation.

Group	Value	95% CI
Pregnant Women With Previous Child With Cardiac Neonatal Lupus	0

Echocardiographic Densities Consistent With EFE Confirmed Postnatally Secondary · After enrollment at 16-18 weeks gestation, then weekly until 26 weeks, biweekly to 34 weeks, at birth (approximately 9 months), and at one year follow up (approximately 21 months from enrollment)

(see title)

Group	Value	95% CI
Pregnant Women With Previous Child With Cardiac Neonatal Lupus	0

Fetal Death Not Related to Cardiac Dysfunction Secondary · Up to 9 months

An autopsy with full evaluation of the heart will be encouraged but cannot be mandated. If AV block or evidence of a cardiomyopathy can be "proven," then these will provide the basis for final categorization. If not possible, the death will not be considered a recurrence rate but will be reported.

Group	Value	95% CI
Pregnant Women With Previous Child With Cardiac Neonatal Lupus	0

Cutaneous Neonatal Lupus Secondary · Up to 15 months (at birth - 9 months, and 6 months thereafter)

Group	Value	95% CI
Pregnant Women With Previous Child With Cardiac Neonatal Lupus	4

Prematurity Secondary · At birth (approximately 9 months)

(gestational age \<37 weeks at birth)

Group	Value	95% CI
Pregnant Women With Previous Child With Cardiac Neonatal Lupus	9

Birth Weight <10% in the Context of Gestational Age Secondary · At birth (approximately 9 months)

Group	Value	95% CI
Pregnant Women With Previous Child With Cardiac Neonatal Lupus	1

Abnormal Fluid Collection Secondary · At birth (approximately 9 months)

Group	Value	95% CI
Pregnant Women With Previous Child With Cardiac Neonatal Lupus	0

Adverse events — posted to ClinicalTrials.gov

Time frame: From time of enrollment to six months after delivery.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pregnant Women With Previous Child With Cardiac Neonatal Lupus

Serious: 0/63 (0%)

Deaths: 0/63

Other adverse events (9 terms — click to expand)

Reaction	System	Pregnant Women With Previo…
Maternal rash	Pregnancy, puerperium and perinatal conditions	—
Pre-eclampsia	Pregnancy, puerperium and perinatal conditions	—
Spontaneous miscarriage	Pregnancy, puerperium and perinatal conditions	—
Severe itching	Pregnancy, puerperium and perinatal conditions	—
Fall	Pregnancy, puerperium and perinatal conditions	—
Placental abruption	Pregnancy, puerperium and perinatal conditions	—
Placenta previa	Pregnancy, puerperium and perinatal conditions	—
Abnormal neonatal liver function test lab values	Pregnancy, puerperium and perinatal conditions	—
Right bundle branch block	Pregnancy, puerperium and perinatal conditions	—

Data from ClinicalTrials.gov NCT01379573 adverse events section.

Sponsor's own description

Women with antibodies to proteins called SSA/Ro and or SSB/La face a 2% chance of having a child with a life threatening heart condition regardless of whether they have very active lupus, are in remission, or have only vague symptoms. This heart problem is referred to as congenital heart block (the most serious being third degree complete block) and represents damage thought to be caused by these autoantibodies. The heart beats abnormally slowly and almost all children require permanent pacemakers before the age of 20. Importantly, women who have had one child with heart block have a ten-fold higher risk of having another child with the same heart condition. Unfortunately, even close monitoring by special techniques during pregnancy does not reverse complete heart block once it is observed. Thus, treatments aimed at prevention are critical. This study will evaluate for the first time whether hydroxychloroquine, a drug used by many patients with SLE, prevents the development of this heart condition. Data from laboratory experiments suggests that this drug, which crosses the placenta, may decrease the inflammation initiated by the passage of anti-Ro antibodies to the fetus. The study uses a Simon's 2-Stage design, and plans to enroll 19 patients in Stage 1 and 35 patients in Stage 2 if Stage 1 is successful. Patients can already be on hydroxychloroquine or will be started as soon as pregnancy is confirmed. The hope is that fewer than 3 cases of heart block will occur in Stage 1, and fewer than 6 cases will occur out of all 54 patients if Stage 2 is reached. The results of this study are expected to become an integral part of the counseling of women with anti-Ro/La antibodies who are considering pregnancy.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. Chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases.
   Al-Bari MA. · · 2015 · cited 293× · PMID 25693996 · DOI 10.1093/jac/dkv018
2. Hydroxychloroquine to Prevent Recurrent Congenital Heart Block in Fetuses of Anti-SSA/Ro-Positive Mothers.
   Izmirly P, Kim M, Friedman DM, Costedoat-Chalumeau N, et al · · 2020 · cited 126× · PMID 32674792 · DOI 10.1016/j.jacc.2020.05.045
3. Prevention and treatment in utero of autoimmune-associated congenital heart block.
   Saxena A, Izmirly PM, Mendez B, Buyon JP, et al · · 2014 · cited 70× · PMID 25050975 · DOI 10.1097/crd.0000000000000026
4. Pregnancy and autoimmune connective tissue diseases.
   Marder W, Littlejohn EA, Somers EC. · · 2016 · cited 50× · PMID 27421217 · DOI 10.1016/j.berh.2016.05.002
5. Electrocardiographic QT Intervals in Infants Exposed to Hydroxychloroquine Throughout Gestation.
   Friedman DM, Kim M, Costedoat-Chalumeau N, Clancy R, et al · · 2020 · cited 17× · PMID 32907357 · DOI 10.1161/circep.120.008686
6. No histologic evidence of foetal cardiotoxicity following exposure to maternal hydroxychloroquine.
   Friedman D, Lovig L, Halushka M, Clancy RM, et al · · 2017 · cited 8× · PMID 28598777