An Observational Pregnancy Safety Study in Women Who Were Exposed to the Drug Nifurtimox During Pregnancy to Learn About the Risk of Pregnancy Complications and About the Mother's and Baby's Health

Study Overview
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Brief Summary
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This is an observational study in which data from women with Chagas disease who will take or have already taken nifurtimox during pregnancy and the impact on their babies are studied. Chagas disease is an inflammatory, infectious disease caused by the parasite Trypanosoma cruzi. This parasite is mainly spread by insects called triatomine bug. If Chagas disease is left untreated, it can later cause e.g. serious heart and digestive problems. Nifurtimox has been used for more than 50 years to treat Chagas disease in children and adults. It is not recommended to be used during pregnancy as data from animal studies indicate that it may harm the baby. Currently, there are not enough data to know if this is also the case in humans. In this study, researchers want to collect data on the safety of nifurtimox use in pregnant women. To do this, researchers will collect the following information: Birth defects (abnormal and problematic structures or functions, a child is born with) Pregnancy outcomes (like live birth, preterm birth, still birth/death of the unborn baby, miscarriage, or abortion) Certain health problems of the child up to 12 months of age Certain health problems of the women experienced during pregnancy The data will be collected from different sources including telephone calls with the women or their doctor, CRFs (case reprt forms) or from medical records The researchers will compare the proportion of children with birth defects, pregnancy outcomes or certain health problems of the child or the women during pregnancy with available data on these outcomes in the general population. The study will run for approximately 10 years.

Official Title
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Observational Pregnancy Safety Study of Women Exposed to Nifurtimox During Pregnancy to Describe the Risk of Pregnancy and Maternal Complications and Other Events of Interest on the Developing Fetus, Neonate, and Infant

Conditions
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Chagas Disease

Intervention / Treatment
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* Drug: Nifurtimox (BAYA2502)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females exposed to at least 1 dose of nifurtimox at any time during pregnancy (i.e., from the first day of the last menstrual period / time of conception to pregnancy outcome). Written informed consent (for adolescents under the age of majority, written informed assent by the pregnant minor (where applicable) and written informed consent by the parent/legal guardian). Exclusion Criteria: None
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pregnant women exposed to nifurtimox<br>The study will examine the effects of nifurtimox on fetuses, neonates and infants through 12 months of age who were exposed to nifurtimox in utero and maternal complications of pregnancy in women who were exposed to at least one dose of nifurtimox during pregnancy. | Drug: Nifurtimox (BAYA2502)<br>* At least 1 dose of nifurtimox<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Congenital Malformations (birth defects) | any major structural defect diagnosed with signs/symptoms, using the selected major congenital anomalies list extracted from the Birth defects surveillance: a manual, CDC. on a case-by-case basis, through evaluator review and agreement from external advisors (if required), any structural defect (that satisfy criterion 1 or 2) detected in the prenatal evaluation of a pregnancy or in the gross or pathologic examination of an abortus, fetus, or deceased infant will be included, if available, to increase the sensitivity of pregnancy study monitoring. | Up to pregnancy week 40 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Events of Interest in Neonates and Infants through 12 Months of Age: Hospitalizations for serious illness |  | Up to 12 months of age | 
| Events of Interest in Neonates and Infants through 12 Months of Age: Medications |  | Up to 12 months of age | 
| Events of Interest in Neonates and Infants through 12 Months of Age: Growth and development milestones | Apgar Scale, CDC Growth Calculators, Cognitive Checklists, ASD (autism spectrum disorder) Tool | Up to 12 months of age | 
| Events of Interest in Neonates and Infants through 12 Months of Age: Neonatal or infant mortality |  | Up to 12 months of age | 
| Maternal Complications: Premature rupture of membranes (PROM) |  | Up to pregnancy week 40 | 
| Maternal Complications: Preeclampsia |  | Up to pregnancy week 40 | 
| Maternal Complications: Severe pregnancy-induced hypertension (PIH) |  | Up to pregnancy week 40 | 
| Maternal Complications: Proteinuria |  | Up to pregnancy week 40 | 
| Maternal Complications: Gestational diabetes |  | Up to pregnancy week 40 | 
| Maternal Complications: Measures of fetal growth deficiency (small for gestational age) |  | Up to pregnancy week 40 | 
| Spontaneous abortion | Any loss of a fetus due to natural causes less than 20 weeks gestation as a spontaneous abortion (WHO/CDC/ICBDSR, 2014). If available, data from gross or pathological examination of the abortus or fetus will be evaluated for structural defects. | Up to 20 weeks | 
| Elective/Induced abortion | Elective or induced abortion is the termination of pregnancy through medical or surgical procedures (ACOG, 2014) (WHO, 2014) If available, data from gross or pathological examination of the abortus or fetus will be evaluated for structural defects. | Up to pregnancy week 40 | 
| Fetal death/Still birth | Fetal death or stillbirth refers to fetuses born dead at > 20 weeks gestation or weighing > 500 grams. Fetal death occurring > 20 weeks but less than 28 weeks gestation is considered an early fetal loss. Fetal death occurring > 28 weeks is considered a late fetal loss (ACOG, 2014). If available, data from gross or pathological examination of the abortus or fetus will be evaluated for structural defects. • The study will make the final classification between fetal death/still birth and spontaneous abortion based on gestational age and weight. If these parameters are not available, the study will accept the classification indicated by the HCP. | More than 20 weeks gestation or weighing less than 500 grams | 
| Preterm delivery | Births delivered prior to 37 completed weeks of gestation per 100 births. Gestational age is based on the obstetric estimate of gestation (CDC). | Prior to 37 completed weeks of gestation | 
| Live Birth | A live birth refers to a complete expulsion from its mother of a surviving neonate breathing or showing any evidence of life such as a heartbeat, umbilical cord pulsation, or definite movement of voluntary muscles, whether the umbilical cord has been cut or the placenta is attached (WHO, 2014). | Up to pregnancy week 40 | 
| Ectopic or Molar Pregnancy | Any reported ectopic or molar pregnancy will be sub-classified in the respective pregnancy outcome including induced abortion, live birth, or spontaneous pregnancy loss. CDC National Center for Health Statistics surveillance system (NCHS, 2004 ). | Up to pregnancy week 40 |