S. Japonicum and Pregnancy Outcomes: A Randomized, Double Blind, Placebo Controlled Trial (RCT)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 370
- 试验地点
- 1
- 主要终点
- Mean Newborn Birth Weight
研究概览
简要总结
The purpose of the study is to understand whether the drug praziquantel (PZQ) is safe for the mother and developing baby when the mother has schistosomiasis (a type of worm) infection, and whether the drug may improve the mother's and baby's health. The usual practice is to wait until after a mother has finished breast feeding before giving the medicine. Approximately 375 infected pregnant women, ages 18 and over, in endemic villages in Leyte, The Philippines will participate. Study volunteers 12-16 weeks pregnant will be given PZQ or an inactive pill (placebo) and stay in the hospital overnight. Small blood samples will be collected before and after the medication is taken. Three stool and urine samples will be taken during a total of 7 study visits. An ultrasound image (picture or outline of the unborn baby) will be performed. When the baby is born, a small blood sample will be taken. Mother and baby will be followed for up to 8 months before the baby is born and 1 month after.
详细描述
This double-blind, placebo-controlled study will investigate praziquantel (PZQ) for the treatment of Schistosomiasis japonicum in pregnant women living in endemic villages of Leyte, The Philippines. The study will enroll 375 pregnant women, ages 18 and over, infected with S. japonicum. The primary study objective is to quantify the efficacy of PZQ treatment for S. japonicum at 12-16 weeks gestation on newborn birth weight among live births. This will be assessed by measuring birth weight within 96 hours of delivery to 10 grams. The secondary objectives are to: 1) assess treatment efficacy with respect to maternal and newborn nutritional status and maternal parasitologic response to treatment; 2) collect preliminary safety and toxicity data on use of PZQ among pregnant women and their newborns; 3) identify extra-placental mechanisms mediating the hypothesized beneficial effect of PZQ on birth outcomes; and 4) identify extra-placental mechanisms mediating the hypothesized beneficial effect of PZQ on birth outcomes. Participants will be involved in study related procedures for 9 months (8 months pre-natally and 1 month post-natally) for mother and infant. This study is linked to DMID protocol 08-0049.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •For screening:
- •Female, age 18 or over.
- •Present to a study midwife with suspected pregnancy.
- •Live in a study village.
- •For the main study:
- •Infected with S. japonicum.
- •Pregnancy as determined by urine pregnancy test.
- •Age 18 or older.
- •Participant is otherwise healthy as determined by history, physical exam, ultrasound and laboratory assessment.
- •Pregnancy between 12-16 weeks gestation.
- •Ability to provide informed consent to participate.
排除标准
- •Presence of significant disease/illness that is either acute or chronic. This will be defined by history, physical examination, ultrasound and laboratory assessment. In particular:
- •History of seizures or other neurologic disorder, chronic medical problem determined by history or physical examination, e.g. active hepatitis, tuberculosis, heart disease.
- •Grade 3 or higher laboratory abnormality of blood urea nitrogen (BUN), Creatinine, bilirubin, white blood cell count, or platelet count will warrant exclusion. Grade 2 or higher abnormality of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) will warrant exclusion. For hemoglobin, women with severe anemia defined as hemoglobin less than 7.0 g/dl will be excluded.
- •Women with myoma on ultrasound that are sub-mucosal or women with myoma that is in any location and greater than 5 cm in size.
- •Women with congenital anomalies of the reproductive tract that would be expected to cause decreased fetal weight or greatly increase the risk of prematurity such as duplicate uterus, uterine septum.
- •For less clear cases, the researchers will define significant illness as one that significantly alters a woman's ability to perform activities of daily living, causes symptoms at least two days per week, or necessitates regular use of medication. In the case of acute medical conditions such as urinary tract infection, pneumonia, febrile illness, enrollment may be postponed until the illness is successfully treated (not currently on any medication for the illness) or the illness self resolves if this occurs before 16 weeks gestation.
- •Presence of cysts in the eye suggestive of neurocysticercosis.
- •Regular use of a medication for a chronic medical condition.
- •History of severe allergic reaction (anaphylaxis, facial swelling, or difficulty breathing) or seizure with praziquantel administration.
- •Fetus has congenital anomaly determined by 12-16 week ultrasound or is determined to be nonviable (e.g. blighted ovum).
- •Twin or higher order pregnancy.
- •Woman has been enrolled into this study for a previous pregnancy.
- •Inability to comprehend study procedures and provide informed consent due to limited cognitive abilities or other, or refuses to provide informed consent.
研究组 & 干预措施
Control
Placebo at 12-16 weeks gestation.
干预措施: Placebo (Other)
Praziquantel
Praziquantel at 12-16 weeks gestation.
干预措施: Praziquantel (Drug)
结局指标
主要结局
Mean Newborn Birth Weight
时间窗: Within 24 hours of delivery.
Birth weight was collected for live infants at the time of delivery by a trained midwife, or within 24 hours of delivery for participants who chose to deliver at home with a helot, a birth attendant without formal training.
次要结局
- Median Change in Maternal Transferrin Receptor:Ferritin Ratio From 14 to 32 Weeks Gestation(14 weeks and 32 weeks gestation)
- Newborn Median Serum Transferrin Receptor:Ferritin Ratio(0-6 days after delivery.)
- Median Maternal Hepcidin at 32 Weeks Gestation(32 weeks gestation)
- Number of Participants Whose Pregnancy Resulted in a Live Birth(At delivery)
- Mean Change in Maternal Hemoglobin From 14 to 32 Weeks Gestation(14 weeks and 32 weeks gestation)
- Mean Change in Maternal Weight From 14 to 32 Weeks Gestation(14 and 32 weeks gestation)
- Mean Change in Maternal Thigh Skinfold Thickness From 14 to 32 Weeks Gestation(14 and 32 weeks gestation)
- Number of Subjects With Reduction in S. Japonicum Egg Counts From Screening to 22 Weeks Gestation of Greater Than 90 Percent(Screening and 22 weeks gestation)
- Number of Participants Reporting Serious Adverse Events Within 24 Hours of Dosing(Within 24 hours of dosing)
- Number of Participants Experiencing Fetal Loss by Abortion(After dosing and before 20 weeks gestation)
- Number of Participants Reporting Abnormalities in Hematology Assessments Within 24 Hours of Dosing(Just before and 24 hours after dosing)
- Number of Participants Reporting Abnormalities in Clinical Chemistry Assessments Within 24 Hours of Dosing(Just before and 24 hours after dosing)
- Number of Participants Whose Infant Was Born With Congenital Anomalies(At delivery, within 2-6 days of delivery, and at 28 days)
- Number of Participants With Pre-eclampsia(22 weeks and 32 weeks)
- Maternal Serum Cytokine Levels of TNF-alpha, TNF-alpha Receptors I and II, IL-1, and IL-6(At 32 weeks gestation)
- Placental Blood Cytokine Levels(At delivery)
- Cytokeratin 18 Neo-epitope Staining as a Measure of Apoptosis(32 weeks gestation)
- Praziquantel Pharmacokinetic Concentrations(4.5 and 8 hours after the first praziquantel dose (subjects assigned to an even study number) or 6 and 10 hours after the first praziquantel dose (subjects assigned to an odd study number).)
- 4-hydroxy Praziquantel Pharmacokinetic Concentrations(4.5 and 8 hours after the first praziquantel dose (subjects assigned to an even study number) or 6 and 10 hours after the first praziquantel dose (subjects assigned to an odd study number).)