Clinical trial NCT00486863: S. Japonicum and Pregnancy Outcomes
Official title: S. Japonicum and Pregnancy Outcomes: A Randomized, Double Blind, Placebo Controlled Trial (RCT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schistosomiasis
Keywords: Philippines, Schistosoma japonicum, Schistosomiasis, pregnant women, fetuses, 08-0049
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2007-06-15
Enrollment: 370
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

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.

Exclusion Criteria:

* 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:

  1. History of seizures or other neurologic disorder, chronic medical problem determined by history or physical examination, e.g. active hepatitis, tuberculosis, heart disease.
  2. 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.
  3. 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.
  4. 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.
  5. 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.

Primary outcomes:
measure: Mean Newborn Birth Weight
timeFrame: Within 24 hours of delivery.
Secondary outcomes:
measure: Number of Participants Whose Pregnancy Resulted in a Live Birth
timeFrame: At delivery
measure: Mean Change in Maternal Hemoglobin From 14 to 32 Weeks Gestation
timeFrame: 14 weeks and 32 weeks gestation
measure: Median Change in Maternal Transferrin Receptor:Ferritin Ratio From 14 to 32 Weeks Gestation
timeFrame: 14 weeks and 32 weeks gestation
measure: Median Maternal Hepcidin at 32 Weeks Gestation
timeFrame: 32 weeks gestation
measure: Mean Change in Maternal Weight From 14 to 32 Weeks Gestation
timeFrame: 14 and 32 weeks gestation
measure: Mean Change in Maternal Thigh Skinfold Thickness From 14 to 32 Weeks Gestation
timeFrame: 14 and 32 weeks gestation
measure: Newborn Median Serum Transferrin Receptor:Ferritin Ratio
timeFrame: 0-6 days after delivery.
measure: Number of Subjects With Reduction in S. Japonicum Egg Counts From Screening to 22 Weeks Gestation of Greater Than 90 Percent
timeFrame: Screening and 22 weeks gestation
measure: Number of Participants Reporting Serious Adverse Events Within 24 Hours of Dosing
timeFrame: Within 24 hours of dosing
measure: Number of Participants Experiencing Fetal Loss by Abortion
timeFrame: After dosing and before 20 weeks gestation
measure: Number of Participants Reporting Abnormalities in Hematology Assessments Within 24 Hours of Dosing
timeFrame: Just before and 24 hours after dosing
measure: Number of Participants Reporting Abnormalities in Clinical Chemistry Assessments Within 24 Hours of Dosing
timeFrame: Just before and 24 hours after dosing
measure: Number of Participants Whose Infant Was Born With Congenital Anomalies
timeFrame: At delivery, within 2-6 days of delivery, and at 28 days
measure: Number of Participants With Pre-eclampsia
timeFrame: 22 weeks and 32 weeks
measure: Maternal Serum Cytokine Levels of TNF-alpha, TNF-alpha Receptors I and II, IL-1, and IL-6
timeFrame: At 32 weeks gestation
measure: Placental Blood Cytokine Levels
timeFrame: At delivery
measure: Cytokeratin 18 Neo-epitope Staining as a Measure of Apoptosis
timeFrame: 32 weeks gestation
measure: Praziquantel Pharmacokinetic Concentrations
timeFrame: 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).
measure: 4-hydroxy Praziquantel Pharmacokinetic Concentrations
timeFrame: 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).
Other outcomes:
Locations:
city: Muntinlupa City
country: Philippines
facility: Research Institute for Tropical Medicine - Health Compound
state: National Capital Region
Study officials:
References:
citation: Salam RA, Das JK, Bhutta ZA. Effect of mass deworming with antihelminthics for soil-transmitted helminths during pregnancy. Cochrane Database Syst Rev. 2021 May 17;5(5):CD005547. doi: 10.1002/14651858.CD005547.pub4.
citation: Colt S, Jarilla B, Baltazar P, Tallo V, Acosta LP, Wu HW, Barry CV, Kurtis JD, Olveda RM, Friedman JF, Jiz MA. Effect of maternal praziquantel treatment for Schistosoma japonicum infection on the offspring susceptibility and immunologic response to infection at age six, a cohort study. PLoS Negl Trop Dis. 2021 Apr 16;15(4):e0009328. doi: 10.1371/journal.pntd.0009328. eCollection 2021 Apr.
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citation: Blake RA, Park S, Baltazar P, Ayaso EB, Monterde DB, Acosta LP, Olveda RM, Tallo V, Friedman JF. LBW and SGA Impact Longitudinal Growth and Nutritional Status of Filipino Infants. PLoS One. 2016 Jul 21;11(7):e0159461. doi: 10.1371/journal.pone.0159461. eCollection 2016.
citation: Olveda RM, Acosta LP, Tallo V, Baltazar PI, Lesiguez JL, Estanislao GG, Ayaso EB, Monterde DB, Ida A, Watson N, McDonald EA, Wu HW, Kurtis JD, Friedman JF. Efficacy and safety of praziquantel for the treatment of human schistosomiasis during pregnancy: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2016 Feb;16(2):199-208. doi: 10.1016/S1473-3099(15)00345-X. Epub 2015 Nov 2.