UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Preventive Approach to Congenital Heart Block with Hydroxychloroquine: an investigator-initiated clinical trial using telemedicine in Japan
Title of the study (Brief title)	J-PATCH
Region	Japan

Condition
Condition	Pregnant women with previous child with cardiac neonatal lupus
Classification by specialty	Clinical immunology Pediatrics
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To evaluate whether hydroxychloroquine use during pregnancy prevents congenital heart block in pregnant women with previous child with cardiac neonatal lupus
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Explanatory
Developmental phase	Phase III

Assessment
Primary outcomes	Advanced heart block (type II or III) [screening fetal echocardiography: biweekly from 18 weeks to 26 weeks]
Key secondary outcomes	1)Prolonged PR interval (>150msec) [screening fetal echocardiography: biweekly from 18 weeks to 26 weeks, EKG at birth, and at 6 months and one year follow up] 2) Any sign of myocardial injury, without change in cardiac rate or rhythm [fetal echocardiography: biweekly from 18 weeks to 26 weeks] 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. 3) Echocardiographic densities consistent with EFE confirmed postnatally [screening fetal echocardiography: biweekly from 18 weeks to 26 weeks] 4) Fetal death not related to cardiac dysfunction 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. 5) NL rash [at birth, at 6 months and 1 year follow up] 6) Prematurity [At birth] (gestational age <37 weeks at birth) 7) Birth weight <10% in the context of gestational age [At birth] 8) Abnormal fluid collection [At birth]

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Prevention
Type of intervention	Medicine
Interventions/Control_1	Drug: Hydroxychloroquine Those who meet eligibility criteria will receive 400mg/d of HCQ (two 200mg pills) Mothers already on HCQ will remain on 400mg/d, or escalate to 400mg/d if taking less than 400mg/d.
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	18 years-old <=
Age-upper limit	45 years-old >=
Gender	Female
Key inclusion criteria	1. Mothers must have anti-SSA/Ro and/or anti-SSB/La Ab documented. 2. Mothers must have a previous child with cardiac NL, defined herein as: the presence of heart block (1st, 2nd, or 3rd degree) documented by electrocardiogram (EKG), echocardiogram, pacemaker, or statement in the medical record, and/or; presence of cardiac injury, which specifically includes autopsy evidence of a mononuclear infiltrate in the endocardium, myocardium, and pericardium and/or endocardial fibroelastosis (EFE) on echocardiogram always associated with cardiac dysfunction. 3. Pregnancy <=10 weeks. 4. Mother may be taking <=20 mg prednisone 5. Mother may be asymptomatic, or have a rheumatic disease such as SLE or SS. 6. Mother may or may not already be taking HCQ.
Key exclusion criteria	1. Mother does not have Ab to SSA/Ro or SSB/La. 2. Identification of any of the following structural lesions considered causal for CHB, i.e., L-transposition of the great arteries, polysplenia, atrioventricular septal defects, etc) 3. Mother is taking fluorinated steroids (dexamethasone, betamethasone) 4. Contraindication of HCQ: history of hypersensitivity to HCQ, retinopathy (except SLE retinopathy)or maculopathy 5. lack of cooperation of local rheumatologists, obstetricians, and pediatric cardiologists 6. difficulty in visiting hospital or home-visit
Target sample size	20

Research contact person
Name of lead principal investigator	Naoto Yokogawa, MD
Organization	Tokyo Metropolitan Tama Medical Center
Division name	Department of Rheumatic Diseases
Address	2-8-29, Musashidai, Fuchu-shi, Tokyo, JAPAN 183-8524
TEL	042-323-5111
Email	yokogawan@aol.com

Public contact
Name of contact person	Naoto Yokogawa, MD
Organization	Tokyo Metropolitan Tama Medical Center
Division name	Department of Rheumatic Diseases
Address	2-8-29, Musashidai, Fuchu-shi, Tokyo, JAPAN 183-8524
TEL	042-323-5111
Homepage URL
Email	yokogawan@aol.com

Sponsor
Institute	Tokyo Metropolitan Tama Medical Center
Institute
Department

Funding Source
Organization	The Ministry of Education,Culture,Sports,Science and Technology (MEXT)
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	東京都立多摩総合医療センター

Other administrative information
Date of disclosure of the study information	2017 Year 09 Month 18 Day

Progress
Recruitment status	Open public recruiting
Date of protocol fixation	2017 Year 09 Month 18 Day
Anticipated trial start date	2017 Year 09 Month 18 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2017 Year 09 Month 03 Day
Last modified on	2019 Year 03 Month 10 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000033124