SAINT: Safe Induction of Labor Trial (SAINT)

A Double-blind Randomized Placebo-controlled Four-arm Trial to Assess the Efficacy of Oral Bicarbonate and Intravenous Butylscopolamine Bromide to Facilitate Spontaneous (Non-operative) Delivery in Pregnant Female Participants With Induction of Labor

Over the past years, the rates of labor induction have increased steadily, and at present more than one in four births occurs after induced labor in Norway. There is evidence that several groups of women benefit from labor induction, including those with preeclampsia (1), postdate pregnancy, diabetes, a large-for-gestational-age fetus, gestational diabetes, prelabor rupture of membranes at term, preterm prelabor rupture of membranes, twin pregnancy and intrahepatic cholestasis of pregnancy.

At the same time, induction of labor is an independent risk factor for adverse obstetric outcomes, including cesarean section, operative vaginal delivery, chorioamnionitis, labor dystocia, prolonged labor, uterine rupture, and neonatal pH < 7.10. A recent Norwegian nationwide clinical practice pilot evaluation demonstrated that the rate of intervention was high, and that as many as 44% of women with labor induction experienced operative delivery.

Given that induction of labor is a common procedure (15 000 women per year in Norway) and increases risk of several major obstetric complications, interventions that may reduce operative births and facilitate safe deliveries are highly warranted.

Bicarbonate and butylscopolamine bromide have been used in smaller studies in order to shorten labor. The medications seem to be safe with a low frequency of adverse events.

The rationale of the present study is therefore 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.

Study Overview

• Status: Recruiting
• Conditions: Pregnancy Related; Labor Complication; Induced; Birth
• Intervention / Treatment: Drug: Buscopan 20 MG/ML Injectable Solution; Drug: Sodium bicarbonate; Drug: Placebo; Drug: Nacl 0.9%

• Study Type: Interventional
• Enrollment (Estimated): 3000
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Trond M Michelsen, MD PhD; Phone Number: +4723070000; Email: trmi1@ous-hf.no

Study Locations

• Norway
  • Lørenskog, Norway
    • Recruiting
    • Akershus University Hospital
    • Contact: Camilla Haavaldsen, MD, PhD
  • Oslo, Norway, 0424
    • Recruiting
    • Oslo University Hospital Rikshospitalet
    • Contact: Trond M Michelsen, MD, PhD; Phone Number: +472307000; Email: trmi1@ous-hf.no
    • Contact: Ingvil K Sorbye, MD, PhD; Phone Number: +4723072640; Email: isorbye@ous-hf.no
  • Oslo, Norway
    • Recruiting
    • Oslo University Hospital Ullevål
    • Contact: Anne F Jacobsen, MD, PhD; Email: uxafja@ous-hf.no
  • Stavanger, Norway
    • Recruiting
    • Stavanger University Hospital
    • Contact: Ragnar K Sande, MD, PhD
  • Tromsø, Norway
    • Recruiting
    • The University Hospital of North Norway
    • Contact: Åse T Pettersen, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

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).

Exclusion Criteria:

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) >100 U/L. Participation can still be considered for participants with ALAT >100 U/L if explained by obstetric cholestasis or HELLP syndrome.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Buscopan and bicarbonate	Drug: Buscopan 20 MG/ML Injectable Solution; 1 mL intravenously; Drug: Sodium bicarbonate; 4 g orally
Active Comparator: Buscopan and placebo	Drug: Buscopan 20 MG/ML Injectable Solution; 1 mL intravenously; Drug: Placebo; 4g orally; Other Names: Oral Tab
Active Comparator: Placebo and bicarbonate	Drug: Sodium bicarbonate; 4 g orally; Drug: Nacl 0.9%; 1 mL intravenously; Other Names: Intravenous placebo
Placebo Comparator: Placebo and placebo	Drug: Placebo; 4g orally; Other Names: Oral Tab; Drug: Nacl 0.9%; 1 mL intravenously; Other Names: Intravenous placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spontaneous vs operative birth	Number of participants with operative birth as compared to spontaneous birth	Through study completion, an average of one week

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Investigators: Principal Investigator: Trond M Michelsen, MD PhD, Oslo University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2023
• Primary Completion (Estimated): January 31, 2025
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: December 18, 2022
• First Submitted That Met QC Criteria: February 7, 2023
• First Posted (Actual): February 9, 2023

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Obstetric Labor Complications; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Butylscopolammonium Bromide
• Other Study ID Numbers: 235247

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No