Balloon catheter versus misoprostol for the induction of labor following pre-labor rupture of membranes at term
| ISRCTN | ISRCTN10972090 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN10972090 |
| EudraCT/CTIS number | Nil Known |
| Secondary identifying numbers | TYH2019302 |
- Submission date
- 01/02/2021
- Registration date
- 05/02/2021
- Last edited
- 19/12/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Pregnancy and Childbirth
Plain English summary of protocol
Background and study aims:
The rupture of membranes (also known as 'water breaking' due to loss of amniotic fluid via the vagina) usually occurs when a pregnancy has reached full term, either during, or at the beginning of, labor. Pre-labor rupture of membranes (PROM) is when this rupture occurs before labor has begun.
In Finland, almost a third of all deliveries are induced, which means that the labor process is initiated artificially. One of the most common reasons for induction of labor (IOL) is prolonged pre-labor rupture of membranes (prolonged PROM), which is when the membranes rupture but labor does not start within the following 24 h. PROM increases the risk for infection in mothers as well as newborns.
If the cervix is unfavorable when starting IOL (meaning it has not undergone the changes that make the spontaneous onset of labor likely), then priming of the cervix (i.e. softening) can increase the success of IOL and shorten labor duration. Priming can be done either mechanically with a balloon catheter or pharmaceutically (using medication) with misoprostol. Sometimes these methods are used in succession or in conjunction. Both types of priming are safe and efficient without increasing the risk of cesarean section or birth complications.
One concern about the use of balloon catheter for priming after rupture of membranes is that it could potentially lead to an increase of infections, and it is not recommended if patients test positive for GBS (group B Streptococcus- the most common cause of neonatal sepsis). A few small studies appear to disprove this concern.
The current practice in the participating hospital in this study during balloon catheter placement after PROM is the administration of routine antibiotics in advance to prevent possible infections (prophylactic). This was established based on previous studies, however, there is no scientific evidence for this. This routine prophylactic antibiotic use has been questioned due to rising concern about possible short term and long term effects on the newborn.
This study will compare the efficacy and safety of the two different priming methods in participants with prolonged PROM. Additionally, this study will assess the need for antibiotic prophylaxis and the incidence of infections of mothers and newborns in participants where the cervix is primed using the balloon catheter method. Finally, the study will investigate differences in birth experience and patient satisfaction.
Who can participate:
Women at least 18 years of age, in their first or any subsequent singleton pregnancy, with spontaneous rupture of membranes without the onset of labor within 18-48 hours, at term (≥ 37 gestational weeks), who need to be induced, who present with an unfavorable cervix (Bishop’s score <6), whose fetus is in cephalic presentation and who have no colonization of Group B Streptococcus on vaginal and rectal swab.
What does the study involve:
Participation in this study is completely voluntary. Eligible women presenting to the participating hospital with PROM who need induction of labor will be asked to participate in the study. If, after receiving a preliminary information leaflet about the study, they are interested in participating, they will be given further information and asked for signed consent.
The parturient will then be allocated randomly (like a coin toss) to one of the two methods of cervical priming: either using a balloon catheter (mechanical) or misoprostol taken by mouth (using medication).
If the participant is allocated to the balloon catheter group, they will again be randomized (like a coin toss) into one of two groups: to receive a routine antibiotic to treat a possible bacterial infection or no routine antibiotic.
All participants will be asked to fill out a birth experience questionnaire.
What are the possible benefits and risks of participating?
According to national and international guidelines, women with prolonged PROM should be induced, to reduce the adverse effects of prolonged PROM. The priming method (either mechanical or pharmaceutical) is usually chosen at the discretion of the treating obstetrician, under consideration of patient preference. The participants of this study will also need to be induced for PROM. The difference to standard induction of labor outside the study is, that the priming method used will be determined at random rather than participant preference. Since both methods are well established in clinical practice, this should bring no disadvantage or risk to the participant.
The common clinical practice of routine antibiotics during balloon catheter induction is not based on scientific evidence. This study hopes to clarify the need, benefit, and/or risk of antibiotic use during balloon catheter induction.
Where is the study run from?
Department of Obstetrics and Gynaecology of Helsinki University Hospital (Finland)
When is the study starting and how long is it expected to run for?
From August 2020 until February 2028
Who is funding the study?
Helsinki University Hospital (Finland)
Who is the main contact?
1. Heidi Kruit
heidi.kruit@hus.fi
2. Leena Rahkonen
Leena.rahkonen@hus.fi
Contact information
Scientific
Department of Obstetrics and Gynecology
Helsinkin University hospital
Haartmaninkatu 2
Helsinki
00029
Finland
 ORCID ID |
0000-0003-0350-7088 |
|---|---|
| Phone | +358 40 7317068 |
| heidi.kruit@hus.fi |
Scientific
Haartmaninkatu 2
Helsinki
00029
Finland
| Phone | +358 50 427 1248 |
|---|---|
| Leena.rahkonen@hus.fi |
Study information
| Study design | Two-step randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | ISRCTN10972090_PIS_English_6Nov2020.pdf |
| Scientific title | Induction of labor with a balloon catheter versus oral misoprostol following term pre-labor rupture of membranes – a randomized controlled trial |
| Study acronym | ILBOM-PROM |
| Study objectives | 1. Induction of labor after prolonged spontaneous rupture of membranes in a term pregnancy is equally safe with a balloon catheter as with misoprostol 2. In the induction group with a balloon catheter, routine antibiotic prophylaxis does not have an effect on intrapartum infection rates |
| Ethics approval(s) | Approved 02/12/2020, Helsinki University Central Hospital Ethics Committee (HUS Tutkimuseettiset toimikunnat, PO Box 705, Biomedicum Helsinki 2 C 7th floor, Tukholmankatu 8 C, 00029 Helsinki, Finland; +358 50 427 9493; piia.paavilainen@hus.fi), ref: HUS/2549/2020 |
| Health condition(s) or problem(s) studied | Premature rupture of membranes with the onset of labor more than 24 hours following rupture, prolonged rupture of membranes at term with an unfavorable cervix |
| Intervention | Randomization is performed by computer-sequenced block randomization technique in a two-step process, part A and B. Patients are randomized in part A into the method of cervical priming (balloon catheter or oral misoprostol), and in part B (only if they are allocated to balloon catheter priming) into prophylactic antibiotics or no prophylactic antibiotics. Part A of randomization (method of cervical priming) is performed 18-48 h after spontaneous rupture of membranes, if the parturient does not have vaginal or rectal colonization of Group B Streptococcus (assessed using a swab test), the cervix is deemed unfavorable (Bishop score <6), and regular labor contractions have not yet started. In part A the parturient is allocated to one of two groups: 1. Misoprostol group. A 25 µg oral Misoprostol dose will be self-administered by the parturient every 2 h, until regular labor contractions begin, or for a maximum of 8 doses. When the cervix is deemed favorable, amniotomy of a potential intact lower pole is performed. If spontaneous labor contractions do not start after amniotomy, Oxytocin is started, at the earliest 4 h after the last dose of misoprostol. If, after a course of a maximum of 8 doses of misoprostol, the cervix is still deemed unfavorable, the priming of the cervix is considered failed within the framework of the study, and induction of labor will be continued according to local protocol at the discretion of the treating clinician. 2. Balloon catheter group. A single balloon catheter is placed trans-cervically, either with manual insertion during vaginal examination or during speculum examination. The balloon is then inflated with 50-80 ml of sterile saline solution. The balloon catheter can remain in place until spontaneous expulsion or for a maximum of 12 h, after which it will be emptied and removed. If, after spontaneous expulsion or removal of the balloon catheter, the cervix is deemed favorable, amniotomy of a potential intact lower pole is performed. If spontaneous labor contractions do not start within 1-2 h of amniotomy, Oxytocin is started. If, after spontaneous expulsion or removal of the balloon catheter, the cervix is still deemed unfavorable, the priming of the cervix is considered failed within the framework of the study, and induction of labor will be continued according to local protocol at the discretion of the treating clinician. Part B of randomization is performed only when the parturient is placed in the balloon catheter group and will be allocated to one of two groups: 1. Routine prophylactic antibiotic group. The parturient will be given, according to hospital protocol, a routine prophylactic antibiotic of G-Penicillin 5 million units at balloon catheter placement. After the initial dose, the parturient will receive a dose of G-Penicillin 2 million units every four hours, until expulsion or removal of the balloon catheter. In the case of Penicillin allergy, the antibiotic of choice is Clindamycin 900mg every eight hours. 2. No routine prophylactic antibiotic group. The parturient receives no routine prophylactic antibiotic for the duration of the retention of the balloon catheter. All participants receive, on admission/at induction, the CEQ2 birth experience questionnaire and will be asked to fill it out within one month of delivery and return it as soon as possible. The questionnaire is available in Finnish, Swedish, and English. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | misoprostol, procaine benzylpenicillin, clindamycin |
| Primary outcome measure | 1. Incidence of different modes of delivery (vaginal birth, assisted vaginal birth, or caesarean section), maternal infection, and newborn infection collected from patient records between hospital admission and discharge |
| Secondary outcome measures | 1. Maternal complications of delivery (such as retention of placenta, hemorrhage, birth canal tears, and intrapartum or postpartum infection) collected from patient records between hospital admission and discharge 2. Primary assessment of the newborn measured using Apgar score at 1 and 5 min after birth, and using umbilical vein pH and base excess, need for intubation, and need for NICU admission collected from patient records between hospital admission and discharge 3. Birth experience measured using the Childbirth Experience Questionnaire (CEQ2) completed within 1 month after delivery |
| Overall study start date | 01/08/2020 |
| Completion date | 31/12/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target number of participants | 650 |
| Total final enrolment | 180 |
| Key inclusion criteria | 1. Aged ≥18 years 2. Primiparous or multiparous women with singleton pregnancy 3. Gestational age ≥37 weeks (term) 4. Spontaneous rupture of membranes without the onset of labor within 18-48 h 5. Unfavorable cervix (Bishops score <6) 6. Cephalic presentation of fetus 7. No colonization of Group B Streptococcus on vaginal and rectal swab |
| Key exclusion criteria | 1. Pre-term pre-labor rupture of membranes (<37 gestational weeks) 2. Clinical signs of infection (such as vaginitis, chorionamnionitis) 3. Active infection or carrier of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C 4. Type 1 diabetes 5. Group B Streptococcal colonization of vagina and/or rectum (detected by swab test) 6. Any acute condition, maternal or fetal, requiring the immediate delivery of the fetus 7. Intrauterine growth restriction 8. Macrosomia or weight estimation ≥4.5 kg 9. Fetus in any other presentation than cephalic (such as breech or transverse) 10. Previous caesarean section or any other uterotomy (such as myomectomy) 11. Insufficient understanding or language deficiency to comprehend the patient guide and consent form 12. Refusal of participation or refusal for signed consent |
| Date of first enrolment | 01/02/2021 |
| Date of final enrolment | 31/12/2023 |
Locations
Countries of recruitment
- Finland
Study participating centre
Haartmaninkatu 2
Helsinki
00029
Finland
Sponsor information
Hospital/treatment centre
Department of Obstetrics and Gynecology
Haartmaninkatu 2
PL 140
Helsinki
00029
Finland
| Phone | +358 9 4711 |
|---|---|
| heidi.kruit@hus.fi | |
| Website | http://www.hus.fi/en |
"ROR" |
https://ror.org/02e8hzf44 |
Funders
Funder type
Hospital/treatment centre
Government organisation / Local government
- Alternative name(s)
- Helsinki University Central Hospital, HUS
- Location
- Finland
Results and Publications
| Intention to publish date | 30/06/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal. Additional documents will be available upon request from Dr Leena Rahkonen (Leena.rahkonen@hus.fi). |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | 06/11/2020 | 01/03/2021 | No | Yes | |
| Results article | 19/12/2024 | 19/12/2024 | Yes | No |
Additional files
- ISRCTN10972090_PIS_English_6Nov2020.pdf
- Uploaded 01/03/2021
Editorial Notes
19/12/2024: Publication reference added.
11/01/2024: The intention to publish date was changed from 02/02/2028 to 30/06/2024.
10/01/2024: The following changes were made to the study record:
1. Total final enrolment added.
2. The recruitment end date was changed from 01/02/2028 to 31/12/2023.
3. The overall study end date was changed from 01/02/2028 to 31/12/2023.
07/12/2022: A scientific contact was replaced and the plain English summary was updated accordingly.
01/03/2021: The participant information sheet has been uploaded as an additional file.
04/02/2021: Trial’s existence confirmed by Helsinki University Central Hospital Ethics Committee.
