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A Randomized Study Comparing the Efficacy and Safety of Retosiban Versus Atosiban for Women in Spontaneous Preterm Labour

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02292771
Recruitment Status : Terminated (The study was stopped due to the feasibility of recruiting the study in a timely manner)
First Posted : November 17, 2014
Results First Posted : September 10, 2018
Last Update Posted : September 10, 2018
Sponsor:
Collaborator:
PPD
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
The primary objective of this study is to demonstrate the superiority of retosiban to prolong pregnancy in females with spontaneous preterm labor compared with atosiban. This objective is based on the hypothesis that prolonging the time to delivery in the absence of harm may benefit the newborn, particularly in women who experience spontaneous preterm labor at early gestational ages (GA). This study is designed to test this hypothesis through a direct comparison with atosiban, a mixed oxytocin vasopressin antagonist indicated for short-term use to delay imminent preterm birth in women between 24^0/7 and 33^6/7 weeks' gestation in preterm labor. This is a randomized, double-blind, double-dummy study, which consists of 6 phases: Screening, Inpatient Randomized Treatment, Post Infusion Assessment, Delivery, Maternal Post Delivery Assessment, and Neonatal Medical Review. Approximately 330 females will be randomly assigned to retosiban or atosiban treatment in a 1:1 ratio. The duration of any one subject's (maternal or neonatal) participation in the study will be variable and dependent on GA at study entry and the date of delivery.

Condition or disease Intervention/treatment Phase
Obstetric Labour, Premature Drug: Retosiban Drug: Atosiban Drug: Placebo matching retosiban Drug: Placebo matching atosiban Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 97 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Randomized, Double-blind, Multicenter, Phase III Study Comparing the Efficacy and Safety of Retosiban Versus Atosiban Therapy for Women in Spontaneous Preterm Labor
Actual Study Start Date : March 16, 2015
Actual Primary Completion Date : August 25, 2017
Actual Study Completion Date : August 25, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Retosiban + Atosiban Placebo
Participants will receive retosiban 6 milligrams (mg) intravenous (IV) loading dose over 5 minutes, followed by a 6mg/hour continuous infusion over 48 hours. For subjects with an inadequate response after the first hour of treatment, investigators will administer another 6mg IV loading dose and increase the infusion rate to 12 mg/hour for the remainder of the 48-hour treatment period. Participants will also receive placebo infusion matched for the atosiban loading (bolus) dose and continuous infusion to ensure blinding.
Drug: Retosiban
Solution for infusion, consisting of a clear colorless solution of retosiban at a concentration of 15 milligram/milliliter (mg/mL) in 56% volume/volume ethanol/acetate buffer concentrate supplied in 5 mL vial containing 75mg retosiban.

Drug: Placebo matching atosiban
A placebo infusion containing 0.9% NaCl matched for the atosiban loading (bolus) dose and continuous infusion.

Active Comparator: Atosiban + Retosiban Placebo
Participants will receive atosiban in 3 successive stages: an initial bolus dose (6.75 mg) over 1 minute, immediately followed by a continuous infusion at 18 mg/hour for 3 hours, followed by a 6 mg/hour infusion for the remainder of the 48-hour treatment period. Participants will also receive placebo infusion matched for retosiban loading (bolus) dose and continuous infusion to ensure blinding.
Drug: Atosiban
Clear, colorless solution for injection in a 0.9-mL vial containing 6.75 mg of atosiban. Clear, colorless concentrate for solution for infusion in a 5-mL vial containing 37.5 mg atosiban.

Drug: Placebo matching retosiban
A placebo infusion containing 0.9% sodium chloride (NaCl) matched for retosiban loading (bolus) dose and continuous infusion.




Primary Outcome Measures :
  1. Time to Delivery From the Start of Investigational Product (IP) Administration [ Time Frame: Up to 17 weeks ]
    Time to delivery is the number of days from the first dose of study treatment until delivery. The time to delivery was calculated as the days between the delivery and start time of the study treatment infusion using the formula: Time to delivery (days) = (date and time of delivery minus date and time of start of infusion) divided by (24 multiplied by 60). The adjusted mean number of days to delivery along with standard error has been presented. Maternal intent-to-treat (ITT) Population comprised of all mothers randomly assigned to treatment who have been exposed to study treatment irrespective of their compliance to the planned course of treatment.


Secondary Outcome Measures :
  1. Number of Participants With Births Prior to 37 0/7 Weeks Gestation [ Time Frame: Up to 13 weeks ]
    Gestational age (GA) at birth (weeks) is defined as the GA when the baby is born. Participants were considered to have delivered prior to 37 0/7 weeks, that is preterm , if the GA at birth is less than 37 0/7 weeks. The number of participants who delivered prior to 37 0/7 weeks gestation has been presented. Logistic regression model was used to calculate p-values.

  2. Number of Participants With Births at Term [ Time Frame: Up to 17 weeks ]
    Participants were considered to have delivered at term if the gestational age was >=37 0/7. The number of participants who delivered at term, that is, 37 0/7 to 41 6/7 weeks gestation has been presented. Logistic regression model was used to calculate p-values.

  3. Length of Neonatal Hospital Stay [ Time Frame: Up to 28 days post estimated date of delivery (EDD) of 40 0/7 weeks gestation ]
    The length of stay was collected from medical records and was calculated as the days between the delivery date and time and discharge date and time. Log of length of stay was calculated as treatment plus GA at randomization plus established progesterone use based on Analysis of covariance (ANCOVA) model. The p-value was calculated using t-test method. Neonatal ITT Population comprised of all neonates whose mothers were the randomized participants who have been exposed to study treatment, that is, mothers from the ITT Population.

  4. Number of Neonates With Composite Neonatal Morbidity and Mortality [ Time Frame: Up to 28 weeks after EDD (40 weeks gestation) ]
    The neonatal composite endpoint was determined from review of medical records and included the following components: fetal or neonatal death, Respiratory Distress Syndrome (RDS), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC) or isolated perforation, sepsis based on positive blood culture with clinical features of sepsis, meningitis based on positive results for cerebrospinal fluid culture performed as part of infection workup, retinopathy of prematurity (ROP), Intraventricular Hemorrhage (IVH), white matter injury and cerebellar hemorrhage.

  5. Number of Neonates With Any Composite Neonatal Morbidity and Mortality, Excluding RDS [ Time Frame: Up to 28 weeks after EDD (40 weeks gestation) ]
    The neonatal composite endpoint was determined from review of medical records and included the following components: fetal or neonatal death, RDS, BPD, NEC or isolated perforation, sepsis based on positive blood culture with clinical features of sepsis, meningitis based on positive results for cerebrospinal fluid culture performed as part of infection workup, ROP, IVH, white matter injury and cerebellar hemorrhage. Number of neonates with any composite neonatal morbidity and mortality component, excluding RDS has been presented.

  6. Number of Neonates With Each Individual Component of Composite Neonatal Morbidity and Mortality [ Time Frame: Up to 28 weeks after EDD (40 weeks gestation) ]
    The neonatal composite endpoint was determined from review of medical records and included the following components: fetal or neonatal death, RDS, BPD, NEC or isolated perforation, sepsis based on positive blood culture with clinical features of sepsis, meningitis based on positive results for cerebrospinal fluid culture performed as part of infection workup, ROP, IVH, cerebellar hemorrhage and white matter injury included Periventricular Leukomalacia PVL), porencephalic cyst, and persistent ventriculomegaly. Number of neonates with with each individual component of the composite neonatal morbidity and mortality has been presented.

  7. Length of Stay in Specialized Care Unit [ Time Frame: Up to 28 days post EDD (40 0/7 weeks gestation) ]
    Length of neonatal stay in specialized care unit like Intensive Care Unit (ICU) or Neonatal Intensive Care Unit (NICU) are reported.

  8. Number of Newborn Participants With Hospital Readmission [ Time Frame: Up to 28 days of EDD (40 0/7 weeks gestation) ]
    Newborn hospital readmission following hospitalization for birth was obtained from the newborn's medical records. Only those participants with data available at the specified data points were analyzed.

  9. Number of Participants With Births Prior to 28 0/7 Weeks Gestation [ Time Frame: Up to 4 weeks ]
    The number of participants who delivered prior to 28 0/7 weeks gestation has been presented. Only those maternal participants who were randomized prior to 28 0/7 week's gestation and delivered were included.

  10. Number of Participants With Births Prior to 32 0/7 Weeks Gestation [ Time Frame: Up to 8 weeks ]
    Number of participants who delivered prior to 32 0/7 weeks gestation has been presented. Only those maternal participants who were randomized prior to 32 0/7 week's gestation and delivered were included.

  11. Number of Participants With Births Prior to 35 0/7 Weeks Gestation [ Time Frame: Up to 11 weeks ]
    Number of participants who delivered prior to 35 0/7 weeks gestation has been presented. Only those maternal participants who were randomized prior to 35 0/7 week's gestation and delivered were included.

  12. Number of Participants With Births <=7 Days From the First Study Treatment [ Time Frame: Up to 7 days ]
    Number of participants who delivered in less than or equal to 7 days from first dose of study treatment has been presented.

  13. Number of Participants With Births <=48 Hours From the First Study Treatment [ Time Frame: Up to 48 hours ]
    Number of participants who delivered in less than or equal to 48 hours from first dose of study treatment has been presented.

  14. Number of Participants With Births <=24 Hours From the First Study Treatment [ Time Frame: Up to 24 hours ]
    Number of participants who delivered in less than or equal to 24 hours from first dose of study treatment has been presented.

  15. Number of Maternal Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 6 weeks after delivery ]
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; important medical events that may require medical or surgical intervention to prevent one of the other outcomes described before; is associated with liver injury and impaired liver function. Maternal Safety Population comprised of all mothers randomly assigned to treatment who have been exposed to study treatment. The number of maternal participants who experienced at least one non-serious AE and one SAE has been presented.

  16. Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) in Maternal Participants [ Time Frame: Baseline and up to 1 week ]
    SBP and DBP were measured during inpatient randomized treatment phase (15 to 30 minutes, 4 to 8 hours, and 20 to 24 hours after the start of the infusion, at the end of the infusion) and at the post-infusion assessment. Baseline is the last available assessment prior to first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

  17. Change From Baseline in Heart Rate in Maternal Participants [ Time Frame: Baseline and up to 1 week ]
    Heart rate was measured during inpatient randomized treatment phase (15 to 30 minutes, 4 to 8 hours, and 20 to 24 hours after the start of the infusion, at the end of the infusion) and at the post-infusion assessment. Baseline is the last available assessment prior to first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

  18. Change From Baseline in Respiratory Rate in Maternal Participants [ Time Frame: Baseline and up to 1 week ]
    Respiratory rate was measured during inpatient randomized treatment phase (15 to 30 minutes, 4 to 8 hours, and 20 to 24 hours after the start of the infusion, at the end of the infusion) and at the post-infusion assessment. Baseline is the last available assessment prior to first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

  19. Change From Baseline in Temperature in Maternal Participants [ Time Frame: Baseline and up to 1 week ]
    Temperature was measured during inpatient randomized treatment phase (15 to 30 minutes, 4 to 8 hours, and 20 to 24 hours after the start of the infusion, at the end of the infusion) and at the post-infusion assessment. Baseline is the last available assessment prior to first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

  20. Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocytes Count in Maternal Participants [ Time Frame: Baseline and up to 1 week ]
    Blood samples were collected for the evaluation of change in basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelets and leukocytes count. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title). NA indicates standard deviation was not calculable for a single data point.

  21. Change From Baseline in Erythrocytes in Maternal Participants [ Time Frame: Baseline and up to 1 week ]
    Blood samples were collected for the evaluation of change in erythrocytes from Baseline. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title). NA indicates standard deviation was not calculable for a single data point.

  22. Change From Baseline in Hemoglobin and Erythrocyte Mean Corpuscular Hemoglobin Concentration (MCHC) in Maternal Participants [ Time Frame: Baseline and up to 1 week ]
    Blood samples were collected for the evaluation of change in hemoglobin levels and MCHC from Baseline. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus. NA indicates standard deviation was not calculable for a single data point.

  23. Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) and Mean Platelet Volume (MPV) in Maternal Participants [ Time Frame: Baseline and up to 1 week ]
    Blood samples were collected for the evaluation of change in MCV and MPV from Baseline. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title). NA indicates standard deviation was not calculable for a single data point.

  24. Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase (LDH) Levels in Maternal Participants [ Time Frame: Baseline and up to 1 week ]
    Blood samples were collected for the evaluation of change in ALP, ALT, AST, GGT and LDH from Baseline. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title). NA indicates standard deviation was not calculable for a single data point.

  25. Change From Baseline in Albumin and Protein Levels in Maternal Participants [ Time Frame: Baseline and up to 1 week ]
    Blood samples were collected for the evaluation of change in albumin and protein levels from Baseline. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title). NA indicates standard deviation was not calculable for a single data point.

  26. Change From Baseline in Calcium, Chloride, Carbon Dioxide, Glucose, Potassium, Magnesium, Phosphate and Sodium Level in Maternal Participants [ Time Frame: Baseline and up to 1 week ]
    Blood samples were collected for the evaluation of change from Baseline in levels of calcium, chloride, carbon dioxide, glucose, potassium, magnesium, phosphate, and sodium. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title). NA indicates standard deviation was not calculable for a single data point.

  27. Change From Baseline in Direct Bilirubin, Bilirubin, Indirect Bilirubin, Creatinine and Urate Levels in Maternal Participants [ Time Frame: Baseline and up to 1 week ]
    Blood samples were collected for the evaluation of change from Baseline in levels of direct bilirubin, bilirubin, indirect bilirubin, creatinine and urate. Baseline is defined as the last available assessment prior to the first dose of study treatment. Change from Baseline is the post-dose visit value minus Baseline. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title). NA indicates standard deviation was not calculable for a single data point.

  28. Number of Maternal Participants With AEs of Special Interest (AESI) [ Time Frame: Up to 6 weeks post-delivery ]
    Maternal AESI included: maternal death; chorioamnionitis and its complications (clinical chorioamnionitis, preterm premature rupture of membranes, endomyometritis, wound infection, pelvic abscess, bacteremia, septic shock, disseminated intravascular coagulation, and adult RDS); placental abruption; postpartum hemorrhage - postpartum hemorrhage and/or retained placenta and pulmonary edema. The number of participants with at least one AESI has been presented.

  29. Number of Maternal Participants With Disease Related AEs (DRE) [ Time Frame: Up to 6 weeks post-delivery ]
    Maternal DREs included: signs and symptoms of labor discomfort (example, cramping, backache, muscle aches, nausea); subsequent episodes of preterm labor and hospitalization for delivery. The number of participants with at least one DRE has been presented.

  30. Number of Participants With Fetal Non-serious AEs and SAEs [ Time Frame: Up to 17 weeks ]
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; important medical events that may require medical or surgical intervention to prevent one of the other outcomes described before; is associated with liver injury and impaired liver function. The number of participants who experienced at least one non-serious AE and one SAE has been presented.

  31. Number of Participants With Fetal AESI [ Time Frame: Up to 17 weeks ]
    Fetal AESI included: intrauterine fetal demise; category II or III fetal heart rate tracing; and fetal inflammatory response syndrome characterized by cord blood interleukin-6 >11 picogram per milliliter (pg/mL), funisitis, or chorionic vasculitis. The number of participants who experienced at least one AESI has been presented.

  32. Neonatal APGAR Scores [ Time Frame: Up to 5 minutes after birth ]
    APGAR is a quick test to assess the health of new born children. The test is performed at 1 and 5 minutes after birth. APGAR scale is determined by evaluating the new born on five categories (appearance, pulse, grimace, activity and respiration) on a scale from zero to two, then summing up the five values obtained. APGAR score ranges from 0 to 10 where a score of 7 and above is normal. The mean and standard deviation of APGAR scores at one minute and at five minutes of birth has been presented.Only those participants with data available at the specified data points were analyzed.

  33. Weight of Neonates [ Time Frame: Up to 17 weeks ]
    The weight of neonates was obtained from the neonate birth record. The mean weight of neonates and standard deviation has been presented. Only those participants with data available at the specified data points were analyzed.

  34. Head Circumference of Neonates [ Time Frame: Up to 17 weeks ]
    The head circumference was determined from the neonate birth record. Only those participants with data available at the specified data points were analyzed.

  35. Number of Neonatal Participants With Non-serious AEs and SAEs [ Time Frame: Up to 28 days after the EDD of 40 weeks gestation ]
    An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; important medical events that may require medical or surgical intervention to prevent one of the other outcomes described before; is associated with liver injury and impaired liver function. The number of participants who experienced at least one non-serious AE and one SAE has been presented. Neonatal Safety Population consisted of neonates whose mothers received randomized treatment.

  36. Number of Neonatal Participants With AESI [ Time Frame: Up to 28 days after EDD of 40 weeks gestation ]
    Neonatal AESI included: Neonatal death; Asphyxia; Infections (early onset neonatal sepsis, septic shock, pneumonia, meningitis); RDS; Hypotension; IVH/periventricular leukomalacia; Bronchopulmonary dysplasia; Neonatal acidosis; Hyperbilirubinemia; Necrotizing enterocolitis; and Hypoxic ischemic encephalopathy. The number of neonatal participants who experienced at least one AESI has been presented.

  37. Number of Neonatal Participants With DRE [ Time Frame: Up to 28 days after EDD of 40 weeks gestation ]
    The disease related neonatal events occurring in Infants born prior to 37 completed weeks included: apnea (severe), respiratory failure due to fatigue, hypoxia, or air leak from alveolar injury, patent ductus arteriosus, bradycardia, ventriculomegaly, cerebellar hemorrhage, hydrocephalus other than congenital, gastroesophageal reflux, aspiration pneumonia, anemia, retinopathy of prematurity (all stages), hearing disorder, temperature instability and hypoglycemia. The number of participants with at least one DRE has been presented.

  38. Maternal Length of Stay in Hospital [ Time Frame: Up to 28 days post EDD (40 0/7 weeks gestation) ]
    The length of hospital stay associated with hospital admission for preterm labor and term labor/term delivery was collected from review of medical records. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

  39. Number of Participants Admitted to Particular Hospital Unit [ Time Frame: Up to 28 days post EDD (40 0/7 weeks gestation) ]
    Maternal healthcare resource utilization associated with an episode of preterm labor and normal term delivery were collected from the review of medical records. The number of participants who were admitted to a particular hospital unit like general ward, private/semi-private room, recovery, and other has been presented.

  40. Retosiban Clearance [ Time Frame: Day 1 (2 to 4 hours, 10 to 14 hours) and Day 2 (22 to 26 hours, and 48 to 54 hours) post-infusion ]
    Maternal blood samples were collected at the indicated time points for pharmacokinetic analysis. Data is a combined data set. Data is presented for 10 participants from retosiban arm of study 200719 (NCT02377466) and 43 participants from retosiban arm of study 200721 (NCT02292771).

  41. Volume of Distribution of Retosiban [ Time Frame: Day 1 (2 to 4 hours, 10 to 14 hours) and Day 2 (22 to 26 hours, and 48 to 54 hours) post-infusion ]
    Maternal blood samples were collected at the indicated time points for pharmacokinetic analysis. Data is a combined data set. Data is presented for 10 participants from retosiban arm of study 200719 (NCT02377466) and 43 participants from retosiban arm of study 200721 (NCT02292771).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   12 Years to 45 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed and dated written informed consent is required prior to a subject's participation in the study and the performance of any protocol specific procedures. Adolescents aged 12 to 17 years must provide written agreement to participate in the study in accordance with applicable regulatory and country or state requirements. Subjects will also be asked to sign a release for medical records at the time of consenting to allow access to both the maternal and neonatal records including information about delivery and infant care as well as information collected prior to the consent having been signed.
  • Females aged 12 to 45 years, with an uncomplicated, singleton pregnancy and intact membranes in preterm labor (Note: This protocol includes pregnant adolescents, aged 12 to 17 years, as appropriate, based on national or local regulations.).
  • Gestational age between 24^0/7 and 33^6/7 weeks as determined by known fertilization date, either in vitro fertilization or intrauterine insemination, last menstrual period confirmed by the earliest ultrasound prior to 24^0/7 weeks' gestation, or the earliest ultrasound alone prior to 24^0/7 weeks' gestation, whichever is the most accurate method available for each subject. In situations where prenatal ultrasound records are not available at the time the subject presents, the investigator will make every effort to obtain these records (either via computer records, directly from the subject's primary care obstetrician, or via telephone). However, in cases in which these records are not readily available (e.g., off hours, holiday), it is within the investigator's discretion to use GA based on a verbal history from the subject with the intent of getting confirmation from the medical records as soon as possible.
  • Subjects must be diagnosed with preterm labor according to both of the following criteria:

Regular uterine contractions at a rate of >=4 contractions of at least 30 seconds duration during a 30-minute interval confirmed by tocodynamometry

AND at least 1 of the following:

Cervical dilation >=2 centimeter (cm) and <=4 cm by digital cervical examination or If <2 cm dilation by digital cervical examination, a cervical change consisting of an increase of at least 25% effacement or 1 cm dilation

  • Treatment naïve subjects and subjects not adequately responding to tocolytics other than atosiban (e.g., transfers from other care units) during their current episode of preterm labor may be eligible for the study. Historical failure of a tocolytic treatment in a previous episode of preterm labor is not a required inclusion criterion. Tocolytic failure is defined by progressive cervical changes or continuing uterine contractions.

Exclusion Criteria:

  • Fever with a temperature greater than 100.4°fahrenheit (F) (38°Celcius [C]) for more than 1 hour or >=101°F (38.3°C) in the 24 hours prior to the start of study treatment.
  • Women with maternal-fetal conditions that potentially necessitate the need for delivery, such as pre-eclampsia or fetal compromise
  • A fetus with any diagnosis, condition, treatment, or other factor that in the opinion of the investigator has the potential to affect or confound assessments of efficacy or safety (e.g., nonreassuring fetal status, intrauterine growth restriction, major congenital anomaly).
  • Preterm premature rupture of membranes
  • Women with any confirmed or suspected contraindication to prolongation of pregnancy, such as placental abruption, chorioamnionitis, or placenta previa
  • Evidence of polyhydramnios (amniotic fluid index [AFI] >25 cm) or oligohydramnios (AFI <5 cm).
  • Women with co-morbid medical or obstetric conditions that in the opinion of the investigator have the potential to complicate the pregnancy course and outcomes, such as uncontrolled hypertension, uncontrolled diabetes (if known, history of glycosylated hemoglobin >8% at any time during pregnancy), or compromise the safety of the subject, such as underlying cardiovascular disorder (specifically ischemic cardiac disease, congenital heart disease, pulmonary hypertension, valvular heart disease, arrhythmias, and cardiomyopathy).
  • Women with a history of substance abuse or urine drug screen findings suggestive of substance abuse that may either be implicated as the cause of preterm labor (e.g., abuse of cocaine or methamphetamines) or have the potential to complicate the pregnancy outcome (e.g., alcohol abuse or opioid addiction).
  • Women with any diagnosis, condition, treatment, or other factor that in the opinion of the investigator has the potential to affect or confound assessments of efficacy or safety.
  • Women with documented active hepatitis B or hepatitis C viral infection, unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • History of sensitivity to the IPs or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline (GSK)/PPD medical monitor, contraindicates their participation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02292771


  Show 48 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
PPD
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:
Statistical Analysis Plan  [PDF] October 4, 2017
Study Protocol  [PDF] December 21, 2016


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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02292771     History of Changes
Other Study ID Numbers: 200721
First Posted: November 17, 2014    Key Record Dates
Results First Posted: September 10, 2018
Last Update Posted: September 10, 2018
Last Verified: August 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Spontaneous Preterm Labor
retosiban
GSK221149
atosiban
Additional relevant MeSH terms:
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Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications
Vasotocin
Atosiban
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Tocolytic Agents
Reproductive Control Agents
Oxytocics
Vasoconstrictor Agents