E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Nulliparous women with induction of labor at term and a singleton fetus in vertex position |
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E.1.1.1 | Medical condition in easily understood language |
Induction of labor in healthy term pregnancies |
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E.1.1.2 | Therapeutic area | Body processes [G] - Reproductive physiologi cal processes [G08] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To assess the efficacy of oral bicarbonate and intravenous butylscopolamine bromide on facilitating spontaneous (non-operative) delivery in pregnant female participants with induction of labor |
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E.2.2 | Secondary objectives of the trial |
• To assess the efficacy of bicarbonate tablets compared to placebo tablets, intravenous butylscopolamine bromide compared to intravenous placebo and combined bicarbonate tablets and intravenous butylscopolamine bromide compared to placebo tablets and intravenous placebo on - shortening duration of labor - rates of operative vaginal delivery - rates of cesarean section - postpartum hemorrhage - use of oxytocin - urinary retention - anal sphincter injury - Apgar score - pH in umbilical vessels - transfer to NICU - birth experience |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Participants are eligible to be included in the study only if all of the following criteria apply:
1. Participant must be between 18 and 50 years of age at the time of signing the informed consent. 2. Participants who are female, pregnant, nulliparous and at or above 37 weeks of gestation 3. Participants who fulfill hospital criteria for induction of labor, and where a decision to induce labor has been made 4. Participants carrying a fetus in vertex position 5. Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF).
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E.4 | Principal exclusion criteria |
Participants are excluded from the study if any of the following criteria apply: Medical Conditions 1. Multiple gestation 2. Elective cesarean section 3. Spontaneous start of labor 4. Known maternal intestinal stenosis, ileus or megacolon 5. Persisting maternal tachycardia (heart rate > 130 beats per minute) >30 minutes continuously. 6. Known maternal myasthenia gravis 7. Persisting fetal tachycardia (fetal heart rate baseline > 170 beats per minute) >30 minutes continuously. 8. Maternal hypersensitivity to any of the ingredients in IMP (butylscopolamine bromide, bicarbonate or sodium chloride) 9. Women with heart disease who are under surveillance with heart rate monitoring during labor 10. Known fetal heart disease or known fetal malformations in the gastrointestinal system 11. Untreated maternal glaucoma 12. Maternal electrolyte disturbance: severe hyponatremia, severe hypokalemia 13. Maternal moderate/severe kidney failure (stage III-V: glomerulus filtration rate <59 ml/minute/1.73m2 ) 14. Maternal elevated serum creatinine (>90umol/L) 15. Maternal elevated Alanine Aminotransferase (ALAT) >50 U/L
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E.5 End points |
E.5.1 | Primary end point(s) |
• Spontaneous vaginal delivery (no cesarean section, no forceps delivery, no vacuum delivery) vs. operative delivery (dichotomous variable) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Duration from when the participant was given IMP to delivery (time-to-event variable) • Duration from when the participant was given IMP to 10 cm dilatation (time–to-event variable) • Mean cervical dilatation rate, calculated as mean cervical dilatation from IMP is given to 10 cm (continuous variable) • Duration of labor from the onset of active labor (at least 3 cm dilatation) to delivery (time-to-event variable) • Vaginal delivery vs cesarean delivery (dichotomous variable) • Mode of delivery (spontaneous vaginal delivery, vacuum delivery, forceps delivery, or emergency cesarean delivery) (nominal variable) • Amount of oxytocin administered, measured 1. As total time with treatment (continuous variable) 2. As International Units (IU). The midwife measures mL of oxytocin solution given during labor. IU are calculated based on standardized concentration of the infusion solution [10 IU oxytocin in 1000 mL NaCl solution] (continuous variable). • Change in pain score from baseline to 30 minutes after each IMP administration using a Visual Analogue Scale (continuous variable)
• Postpartum hemorrhage (continuous variable) • Postpartum hemorrhage > 500 mL) (dichotomous variable) • Postpartum hemorrhage > 1000 mL) (dichotomous variable) • Postpartum hemorrhage > 1500 mL) (dichotomous variable) • Urinary retention, defined as need for urinary catheter before the participant leaves the delivery ward (dichotomous variable) • Urinary retention, defined as need for urinary catheter before the participant leaves the maternity ward (dichotomous variable) • Urinary retention, defined as need for urinary catheter after the participant leaves the maternity ward (dichotomous variable) • Anal sphincter injury, defined as obstetric anal sphincter injury grade 3 or 4 (dichotomous variable)
• CTG or STAN effects after administration of IMP measured as changes in o Fetal heart rate variability o Basal heart rate o Desceleration o Short term variability • Amnion fluid lactate as measured at baseline and at time of IMP 1,2 and 3 • Apgar score < 7 at 5 minutes and 10 minutes after delivery (dichotomous variables) • pH levels < 7.00 and < 7.10 in umbilical vein and pH levels < 7.00 and < 7.10 in umbilical artery after delivery (dichotomous variables) • Admission to the neonatal intensive care unit (dichotomous variable) • Birth experience measured by the validated questionnaire Child Birth Experience Questionnaire (continuous variables for each sub-category)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
During labor At delivery At maternity ward One month postpartum (birth experience) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the study is defined as the date of the return of the Childbirth Experience Questionnaire, four weeks after delivery for the last participant. A participant is considered to have completed the study if she has completed all phases of the study, including all doses of IMP during labor and delivery.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |