Back to resultsS. Japonicum and Pregnancy Outcomes
Primary Purpose
Schistosomiasis
Status
Completed
Phase
Phase 2
Locations
Philippines
Study Type
Interventional
Intervention
Praziquantel
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Schistosomiasis focused on measuring Philippines, Schistosoma japonicum, Schistosomiasis, pregnant women, fetuses, 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:
- 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.
Sites / Locations
- Research Institute for Tropical Medicine - Health Compound
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Control
Praziquantel
Arm Description
Placebo at 12-16 weeks gestation.
Praziquantel at 12-16 weeks gestation.
Outcomes
Primary Outcome Measures
Mean Newborn Birth Weight
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.
Secondary Outcome Measures
Number of Participants Whose Pregnancy Resulted in a Live Birth
Each participant was followed until delivery to record if the outcome of the pregnancy was a live birth. Live births were defined as the complete expulsion or extraction from its mother of a product of conception, irrespective of the duration of the pregnancy, which, after such separation, breathes or shows any other evidence of life such as heartbeat, umbilical cord pulsation, or definite movement of voluntary muscles, whether the umbilical cord had been cut or the placenta was attached.
Mean Change in Maternal Hemoglobin From 14 to 32 Weeks Gestation
Hemoglobin concentration in a venous blood sample collected at 14 and 32 weeks gestation was measured using a multi-analyte analyzer. Each participant's change in hemoglobin concentration between the two timepoints was determined, and the mean and standard deviation for each group calculated.
Median Change in Maternal Transferrin Receptor:Ferritin Ratio From 14 to 32 Weeks Gestation
To assess total body iron, one needs to assess the storage compartment, which will contain sequestered iron, and the functional compartment, which represents bioavailable iron. Body iron status is defined by the two laboratory measurements that reflect these compartments, ferritin and serum transferrin receptor. The serum transferrin receptor:ferritin ratio has been shown in quantitative phlebotomy studies to provide an accurate assessment of total body iron over the entire range of status. At 14 and 32 weeks gestation, a blood sample was collected for assessment of total body iron by determination of the transferrin receptor:ferritin ratio. Each participant's change in ratio was calculated, and the median and interquartile range were determined for each group.
Median Maternal Hepcidin at 32 Weeks Gestation
Anemia of inflammation was assessed via maternal urine hepcidin levels. In response to inflammation, elevated serum levels of hepcidin is synthesized. Hepcidin causes sequestration of iron from bio-available forms to storage forms such as ferritin and decreases intestinal absorption of iron. Hepcidin was measured in participants' urine at 32 weeks gestation.
Mean Change in Maternal Weight From 14 to 32 Weeks Gestation
Maternal weight gain was assessed by measuring participants' weight in kilograms. The weight increase from 14 to 32 weeks was determined for each participant, and the mean and standard deviation calculated.
Mean Change in Maternal Thigh Skinfold Thickness From 14 to 32 Weeks Gestation
Maternal fat stores were measured by thigh skinfold thickness obtained using a Holtain skinfold caliper. The thickness increase from 14 to 32 weeks was determined for each participant, and the mean and standard deviation calculated.
Newborn Median Serum Transferrin Receptor:Ferritin Ratio
To assess total body iron, the serum transferrin receptor:ferritin ratio was assessed in the infant. At delivery, a heel stick blood sample and a cord blood sample were collected for assessment of total body iron by determination of the transferrin receptor:ferritin ratio.
Number of Subjects With Reduction in S. Japonicum Egg Counts From Screening to 22 Weeks Gestation of Greater Than 90 Percent
Parasitologic response to treatment was evaluated by counting S. japonicum eggs per gram of stool at screening and again at 22 weeks gestation. Success of treatment was pre-specified as greater than 90 percent reduction in egg count from screening to 22 weeks gestation.
Number of Participants Reporting Serious Adverse Events Within 24 Hours of Dosing
Participants were observed in hospital for 24 hours after dosing for serious adverse events. Serious adverse events included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required in-patient hospitalization or prolongation thereof (for reasons other than the 24-hour observation period); resulted in a congenital anomaly/birth defect; or may have jeopardized the participant, or required intervention to prevent one of these outcomes.
Number of Participants Experiencing Fetal Loss by Abortion
Abortion was defined by the protocol as bleeding followed by fetal loss as supported by ultrasound before 20 weeks gestation. Abortion was an important safety outcome measure due to the fact that abortion would occur closer to the time of dosing than miscarriage or stillbirth. Participants were observed in hospital for 24 hours after dosing and asked to return for any bleeding at any time.
Number of Participants Reporting Abnormalities in Hematology Assessments Within 24 Hours of Dosing
Toxicity to maternal bone marrow, kidney, and liver was assessed by laboratory parameters collected just before and 24 hours after dosing. Specifically, blood was drawn just before the dose at 12-16 weeks gestation to determine baseline complete blood count, including white blood count (WBC), platelets, and hemoglobin. Blood was then drawn 24 hours after the second part of the split dose and before discharge from the hospital to assess any changes in these parameters. White blood count was abnormal at or above 10,800 or at or below 3500 cells/square millimeter (sq mm), platelets were abnormal at or below 140,000 cells/sq mm, and hemoglobin was abnormal at or below 10.9 grams/deciliter (g/dL).
Number of Participants Reporting Abnormalities in Clinical Chemistry Assessments Within 24 Hours of Dosing
Toxicity to maternal kidney and liver was assessed by laboratory parameters collected just before and 24 hours after dosing. Specifically, blood was drawn just before the dose at 12-16 weeks gestation to determine baseline blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin. Blood was then drawn 24 hours after the second part of the split dose and before discharge from the hospital to assess any changes in these parameters. Any values that were 1.1 times the upper limit of normal or greater for the parameter were considered abnormal.
Number of Participants Whose Infant Was Born With Congenital Anomalies
The newborn was examined by the midwife at delivery and within 2-6 days of delivery to assess the presence of congenital anomalies and well-being. The newborn was also examined by study pediatrician at 28 days of life.
Number of Participants With Pre-eclampsia
Participants were assessed for the presence of pre-eclampsia at both the 22 and 32 week visits. Pre-eclampsia was defined by the presence of proteinurea (2+ protein on urine dipstick) and a single diastolic blood pressure reading of 100 millimiters of mercury (mm Hg) or above OR more than one reading, four hours apart, of 90 mm Hg or above.
Maternal Serum Cytokine Levels of TNF-alpha, TNF-alpha Receptors I and II, IL-1, and IL-6
Extra-placental mechanisms mediating improved outcomes in the PZQ group were planned to be evaluated with maternal serum cytokine levels, particularly TNF-alpha, TNF-alpha receptors I and II, IL-1, and IL-6. These assays were intended to be performed only if the primary objective of the study was met; therefore, there will be no results reported for this outcome measure.
Placental Blood Cytokine Levels
Cytokine assays were planned to be performed with culture supernatant harvested from placental explant cultures. The cytokines were to be measured with a multi-analyte analyzer. These assays were intended to be performed only if the primary objective of the study was met; therefore, there will be no results reported for this outcome measure.
Cytokeratin 18 Neo-epitope Staining as a Measure of Apoptosis
A study hypothesis was that peripheral serum obtained from S. japonicum infected, treated mothers would induce a lower level of apoptosis (programmed cell death) in cultured trophoblasts as measured by cytokeratin 18 neo-epitope staining compared to peripheral serum obtained from S. japonicum infected, PZQ untreated mothers. This assay was planned to be completed only if the primary objective was met; therefore, there will be no data for this outcome measure.
Praziquantel Pharmacokinetic Concentrations
Two plasma samples were collected during the overnight hospitalization from approximately 200 subjects that remained at the time of study modification to incorporate PK studies. Subjects had samples collected based on one of two sample collection strategies: 4.5 and 8 hr after the first praziquantel dose or 6 and 10 hr after the first praziquantel dose. Subjects randomized to an even study number were assigned to the 4.5 and 8 hour schedule. Subjects randomized to an odd study number were assigned to the 6 and 10 hour schedule. Samples only from subjects randomized to receive praziquantel were analyzed for praziquantel. Samples drawn from subjects randomized to the control group were not analyzed. Praziquantel concentrations (ng/ml) were assayed using high performance liquid chromatography-electrospray mass spectrometry in the University of California at San Diego Pediatric Clinical Pharmacology Laboratory.
4-hydroxy Praziquantel Pharmacokinetic Concentrations
Since pregnancy is associated with increased cytochrome P450 activity and physiologic changes in the gastrointestinal tract that tend to reduce drug absorption, praziquantel pharmacokinetics may be affected by pregnancy. Thus, the metabolite-to-parent drug ratio may serve as a differential marker to help determine if variability in drug exposure following oral administration during pregnancy is due to altered metabolism or drug absorption. Samples that were collected from subjects who were randomized to receive praziquantel were analyzed for praziquantel and 4-hydroxy praziquantel concentrations. Assays were performed using high performance liquid chromatography-electrospray mass spectrometry in the University of California at San Diego Pediatric Clinical Pharmacology Laboratory. Descriptive statistics were obtained for concentrations at each of the four sparse sampling timepoints.
Full Information
NCT ID
NCT00486863
First Posted
June 14, 2007
Last Updated
December 17, 2015
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
1. Study Identification
Unique Protocol Identification Number
NCT00486863
Brief Title
S. Japonicum and Pregnancy Outcomes
Official Title
S. Japonicum and Pregnancy Outcomes: A Randomized, Double Blind, Placebo Controlled Trial (RCT)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
August 2007 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
November 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schistosomiasis
Keywords
Philippines, Schistosoma japonicum, Schistosomiasis, pregnant women, fetuses, 08-0049
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
370 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
Placebo at 12-16 weeks gestation.
Arm Title
Praziquantel
Arm Type
Experimental
Arm Description
Praziquantel at 12-16 weeks gestation.
Intervention Type
Drug
Intervention Name(s)
Praziquantel
Intervention Description
60 mg/kg administered orally given in split dose (30/mg/kg each) separated by 3 hours; over-encapsulated in gelatin capsules. Two capsule sizes will be made which will be differentiated by color; these will contain 300 mg or 150 mg to allow for best dosing by weight.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Made with the same color coded gelatin capsules with the inert compound dextrose.
Primary Outcome Measure Information:
Title
Mean Newborn Birth Weight
Description
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.
Time Frame
Within 24 hours of delivery.
Secondary Outcome Measure Information:
Title
Number of Participants Whose Pregnancy Resulted in a Live Birth
Description
Each participant was followed until delivery to record if the outcome of the pregnancy was a live birth. Live births were defined as the complete expulsion or extraction from its mother of a product of conception, irrespective of the duration of the pregnancy, which, after such separation, breathes or shows any other evidence of life such as heartbeat, umbilical cord pulsation, or definite movement of voluntary muscles, whether the umbilical cord had been cut or the placenta was attached.
Time Frame
At delivery
Title
Mean Change in Maternal Hemoglobin From 14 to 32 Weeks Gestation
Description
Hemoglobin concentration in a venous blood sample collected at 14 and 32 weeks gestation was measured using a multi-analyte analyzer. Each participant's change in hemoglobin concentration between the two timepoints was determined, and the mean and standard deviation for each group calculated.
Time Frame
14 weeks and 32 weeks gestation
Title
Median Change in Maternal Transferrin Receptor:Ferritin Ratio From 14 to 32 Weeks Gestation
Description
To assess total body iron, one needs to assess the storage compartment, which will contain sequestered iron, and the functional compartment, which represents bioavailable iron. Body iron status is defined by the two laboratory measurements that reflect these compartments, ferritin and serum transferrin receptor. The serum transferrin receptor:ferritin ratio has been shown in quantitative phlebotomy studies to provide an accurate assessment of total body iron over the entire range of status. At 14 and 32 weeks gestation, a blood sample was collected for assessment of total body iron by determination of the transferrin receptor:ferritin ratio. Each participant's change in ratio was calculated, and the median and interquartile range were determined for each group.
Time Frame
14 weeks and 32 weeks gestation
Title
Median Maternal Hepcidin at 32 Weeks Gestation
Description
Anemia of inflammation was assessed via maternal urine hepcidin levels. In response to inflammation, elevated serum levels of hepcidin is synthesized. Hepcidin causes sequestration of iron from bio-available forms to storage forms such as ferritin and decreases intestinal absorption of iron. Hepcidin was measured in participants' urine at 32 weeks gestation.
Time Frame
32 weeks gestation
Title
Mean Change in Maternal Weight From 14 to 32 Weeks Gestation
Description
Maternal weight gain was assessed by measuring participants' weight in kilograms. The weight increase from 14 to 32 weeks was determined for each participant, and the mean and standard deviation calculated.
Time Frame
14 and 32 weeks gestation
Title
Mean Change in Maternal Thigh Skinfold Thickness From 14 to 32 Weeks Gestation
Description
Maternal fat stores were measured by thigh skinfold thickness obtained using a Holtain skinfold caliper. The thickness increase from 14 to 32 weeks was determined for each participant, and the mean and standard deviation calculated.
Time Frame
14 and 32 weeks gestation
Title
Newborn Median Serum Transferrin Receptor:Ferritin Ratio
Description
To assess total body iron, the serum transferrin receptor:ferritin ratio was assessed in the infant. At delivery, a heel stick blood sample and a cord blood sample were collected for assessment of total body iron by determination of the transferrin receptor:ferritin ratio.
Time Frame
0-6 days after delivery.
Title
Number of Subjects With Reduction in S. Japonicum Egg Counts From Screening to 22 Weeks Gestation of Greater Than 90 Percent
Description
Parasitologic response to treatment was evaluated by counting S. japonicum eggs per gram of stool at screening and again at 22 weeks gestation. Success of treatment was pre-specified as greater than 90 percent reduction in egg count from screening to 22 weeks gestation.
Time Frame
Screening and 22 weeks gestation
Title
Number of Participants Reporting Serious Adverse Events Within 24 Hours of Dosing
Description
Participants were observed in hospital for 24 hours after dosing for serious adverse events. Serious adverse events included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required in-patient hospitalization or prolongation thereof (for reasons other than the 24-hour observation period); resulted in a congenital anomaly/birth defect; or may have jeopardized the participant, or required intervention to prevent one of these outcomes.
Time Frame
Within 24 hours of dosing
Title
Number of Participants Experiencing Fetal Loss by Abortion
Description
Abortion was defined by the protocol as bleeding followed by fetal loss as supported by ultrasound before 20 weeks gestation. Abortion was an important safety outcome measure due to the fact that abortion would occur closer to the time of dosing than miscarriage or stillbirth. Participants were observed in hospital for 24 hours after dosing and asked to return for any bleeding at any time.
Time Frame
After dosing and before 20 weeks gestation
Title
Number of Participants Reporting Abnormalities in Hematology Assessments Within 24 Hours of Dosing
Description
Toxicity to maternal bone marrow, kidney, and liver was assessed by laboratory parameters collected just before and 24 hours after dosing. Specifically, blood was drawn just before the dose at 12-16 weeks gestation to determine baseline complete blood count, including white blood count (WBC), platelets, and hemoglobin. Blood was then drawn 24 hours after the second part of the split dose and before discharge from the hospital to assess any changes in these parameters. White blood count was abnormal at or above 10,800 or at or below 3500 cells/square millimeter (sq mm), platelets were abnormal at or below 140,000 cells/sq mm, and hemoglobin was abnormal at or below 10.9 grams/deciliter (g/dL).
Time Frame
Just before and 24 hours after dosing
Title
Number of Participants Reporting Abnormalities in Clinical Chemistry Assessments Within 24 Hours of Dosing
Description
Toxicity to maternal kidney and liver was assessed by laboratory parameters collected just before and 24 hours after dosing. Specifically, blood was drawn just before the dose at 12-16 weeks gestation to determine baseline blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin. Blood was then drawn 24 hours after the second part of the split dose and before discharge from the hospital to assess any changes in these parameters. Any values that were 1.1 times the upper limit of normal or greater for the parameter were considered abnormal.
Time Frame
Just before and 24 hours after dosing
Title
Number of Participants Whose Infant Was Born With Congenital Anomalies
Description
The newborn was examined by the midwife at delivery and within 2-6 days of delivery to assess the presence of congenital anomalies and well-being. The newborn was also examined by study pediatrician at 28 days of life.
Time Frame
At delivery, within 2-6 days of delivery, and at 28 days
Title
Number of Participants With Pre-eclampsia
Description
Participants were assessed for the presence of pre-eclampsia at both the 22 and 32 week visits. Pre-eclampsia was defined by the presence of proteinurea (2+ protein on urine dipstick) and a single diastolic blood pressure reading of 100 millimiters of mercury (mm Hg) or above OR more than one reading, four hours apart, of 90 mm Hg or above.
Time Frame
22 weeks and 32 weeks
Title
Maternal Serum Cytokine Levels of TNF-alpha, TNF-alpha Receptors I and II, IL-1, and IL-6
Description
Extra-placental mechanisms mediating improved outcomes in the PZQ group were planned to be evaluated with maternal serum cytokine levels, particularly TNF-alpha, TNF-alpha receptors I and II, IL-1, and IL-6. These assays were intended to be performed only if the primary objective of the study was met; therefore, there will be no results reported for this outcome measure.
Time Frame
At 32 weeks gestation
Title
Placental Blood Cytokine Levels
Description
Cytokine assays were planned to be performed with culture supernatant harvested from placental explant cultures. The cytokines were to be measured with a multi-analyte analyzer. These assays were intended to be performed only if the primary objective of the study was met; therefore, there will be no results reported for this outcome measure.
Time Frame
At delivery
Title
Cytokeratin 18 Neo-epitope Staining as a Measure of Apoptosis
Description
A study hypothesis was that peripheral serum obtained from S. japonicum infected, treated mothers would induce a lower level of apoptosis (programmed cell death) in cultured trophoblasts as measured by cytokeratin 18 neo-epitope staining compared to peripheral serum obtained from S. japonicum infected, PZQ untreated mothers. This assay was planned to be completed only if the primary objective was met; therefore, there will be no data for this outcome measure.
Time Frame
32 weeks gestation
Title
Praziquantel Pharmacokinetic Concentrations
Description
Two plasma samples were collected during the overnight hospitalization from approximately 200 subjects that remained at the time of study modification to incorporate PK studies. Subjects had samples collected based on one of two sample collection strategies: 4.5 and 8 hr after the first praziquantel dose or 6 and 10 hr after the first praziquantel dose. Subjects randomized to an even study number were assigned to the 4.5 and 8 hour schedule. Subjects randomized to an odd study number were assigned to the 6 and 10 hour schedule. Samples only from subjects randomized to receive praziquantel were analyzed for praziquantel. Samples drawn from subjects randomized to the control group were not analyzed. Praziquantel concentrations (ng/ml) were assayed using high performance liquid chromatography-electrospray mass spectrometry in the University of California at San Diego Pediatric Clinical Pharmacology Laboratory.
Time Frame
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).
Title
4-hydroxy Praziquantel Pharmacokinetic Concentrations
Description
Since pregnancy is associated with increased cytochrome P450 activity and physiologic changes in the gastrointestinal tract that tend to reduce drug absorption, praziquantel pharmacokinetics may be affected by pregnancy. Thus, the metabolite-to-parent drug ratio may serve as a differential marker to help determine if variability in drug exposure following oral administration during pregnancy is due to altered metabolism or drug absorption. Samples that were collected from subjects who were randomized to receive praziquantel were analyzed for praziquantel and 4-hydroxy praziquantel concentrations. Assays were performed using high performance liquid chromatography-electrospray mass spectrometry in the University of California at San Diego Pediatric Clinical Pharmacology Laboratory. Descriptive statistics were obtained for concentrations at each of the four sparse sampling timepoints.
Time Frame
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).
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
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:
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.
Facility Information:
Facility Name
Research Institute for Tropical Medicine - Health Compound
City
Muntinlupa City
State/Province
National Capital Region
ZIP/Postal Code
1781
Country
Philippines
12. IPD Sharing Statement
Citations:
PubMed Identifier
33998661
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.
Results Reference
derived
PubMed Identifier
33861768
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.
Results Reference
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PubMed Identifier
31188820
Citation
Abioye AI, McDonald EA, Park S, Joshi A, Kurtis JD, Wu H, Pond-Tor S, Sharma S, Ernerudh J, Baltazar P, Acosta LP, Olveda RM, Tallo V, Friedman JF. Maternal, placental and cord blood cytokines and the risk of adverse birth outcomes among pregnant women infected with Schistosoma japonicum in the Philippines. PLoS Negl Trop Dis. 2019 Jun 12;13(6):e0007371. doi: 10.1371/journal.pntd.0007371. eCollection 2019 Jun.
Results Reference
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PubMed Identifier
29546300
Citation
Abioye AI, Park S, Ripp K, McDonald EA, Kurtis JD, Wu H, Pond-Tor S, Sharma S, Ernerudh J, Baltazar P, Acosta LP, Olveda RM, Tallo V, Friedman JF. Anemia of Inflammation during Human Pregnancy Does Not Affect Newborn Iron Endowment. J Nutr. 2018 Mar 1;148(3):427-436. doi: 10.1093/jn/nxx052.
Results Reference
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PubMed Identifier
27441564
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.
Results Reference
derived
PubMed Identifier
26511959
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.
Results Reference
derived
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S. Japonicum and Pregnancy Outcomes
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