Clinical trial NCT04603859: When to INDuce for OverWeight? (WINDOW)
Official title: When to INDuce for OverWeight? - a Randomised Controlled Trial (WINDOW)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Pregnancy
Obesity
Parturition
Keywords: Induction of labor
Expectant management
Cesarean section
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
name: Randers Regional Hospital
name: Herning Hospital
name: Central Jutland Regional Hospital
name: Nykøbing Falster County Hospital
name: Odense University Hospital
name: Rigshospitalet Juliane Marie Centret
name: Kolding Sygehus
name: Herlev Hospital
name: Hvidovre University Hospital
name: North Zealand's Hospital
name: Zealand University Hospital - Roskilde
First posted: 2020-10-27
Enrollment: 1900
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The rate of overweight and obese women becoming pregnant is increasing. Obesity in pregnancy along with delivery by cesarean section in obese women is associated with several complications as compared to normal weight women. The longer the woman is pregnant, the longer she is at risk. In an otherwise low-risk pregnant woman at term, it is an ongoing clinical dilemma, whether the benefits of elective induction of labor and termination of the pregnancy will outweigh the potential harms from concomitant induction and delivery process. The proposed study is a randomized controlled study of elective induction versus expectant management in obese women. The study will be carried out as a national multicenter study with inclusion of 1900 participants from Danish delivery wards. The null hypothesis is that the caesarean section rate is similar with elective induction of labor at 39 weeks of gestation, compared with expectant management among pregnant women with pre- or early pregnancy BMI≥30.

Detailed description: Background The World Health Organization (WHO) defines overweight as a body mass index (BMI) of ≥25 kg/m2 and obesity as a BMI of ≥30 kg/m2. Overweight and obesity are rising dramatically worldwide. In fertile women, the prevalence of obesity is one third in the United States, 20% in the United Kingdom, and 12-13% in Denmark. The association between obesity in pregnancy and the risk of gestational complications increases with increasing BMI. Among other complications, obesity in pregnancy is associated with increased risk of caesarean delivery. Delivery by caesarean section further adds significant risks of wound infection or other infectious morbidity in obese women as compared to normal weight women. The longer the woman is pregnant, the longer the risk of pregnancy complications remains. In an otherwise low-risk pregnant woman at term, it is an on-going clinical dilemma, whether the benefits of elective induction of labor (eIOL) and termination of the pregnancy will outweigh the potential harms from the concomitant induction and delivery process. Regarding delivery complications, based on data from historical cohorts, eIOL has traditionally been associated with an increased risk of caesarean section and instrumental delivery. Therefore, expectant management has been the preferred clinical option. This interpretation has now been challenged by a randomized trial (ARRIVE) with \>6000 low-risk pregnant women where eIOL at 39 weeks of gestation was associated with lower caesarean delivery rates. There are no randomized studies in obese women, but two larger observational studies did find lower odds of caesarean delivery in obese women with eIOL as compared to awaiting labor onset. Hence, a randomized trial that would compare caesarean delivery among obese women whose labor is induced with those expectantly managed is warranted. The proposed study will provide new and important knowledge into the area of induction of labor among overweight and obese women with potential great international impact for the future raising number of pregnant women in this subgroup.

With this trial, the investigators aim to compare the risk of caesarean section in obese (BMI ≥ 30 kg/m2), but otherwise low-risk women with eIOL as compared to expectant management.

Materials and methods

The study is a multicenter randomized controlled trial with an allocation ratio of 1:1 in the two following arms:

* Intervention arm/elective induction of labor in pregnancy at 39 gestational week and 0 to 3 days: Induction is performed according to local policy for induction of labor.
* Comparison arm/expectant management: Waiting for spontaneous onset of labor unless a situation develops necessitating either induction of labor or caesarean section.

  1900 low-risk pregnant women with a pre- or early pregnancy BMI ≥ 30 carrying a singleton pregnancy will be recruited from the Danish delivery wards. In each trial site, a physician investigator will be responsible for the enrolment, the electronically randomization, and data collection.

The primary endpoint is the caesarean section rate. Among others there will be secondary endpoints on instrumental delivery, onset of labor, methods of induction, perinatal and postpartum complications both maternal and neonatal along with data on women's experience on birth measured by a questionnaire survey four to six weeks post-partum.

Ethics The study will be conducted in accordance with the ethical principles outlined in the latest version of the 'Declaration of Helsinki' and the 'Guideline for Good Clinical Practice' related to experiments on humans. The Central Denmark Region Committee on Biomedical Research Ethics, and The Danish Health Authorities have approved the study.

Perspectives In perspective, more than 39% of the world's population is overweight and 13% are obese by the WHO classification. Pregnant overweight women are at increased risk of pregnancy and delivery complications, and there is a need to improve maternity care for this subgroup of women. The results of this trial have the potential to generate important knowledge for the improvement of delivery in obese women and they will add key information to an on-going discussion of the effects of labor induction before term. Any possible harm or disadvantage to the individual study participant is outweighed by the possible benefit to the increasing number of obese women who will be pregnant in the future.

Eligibility criteria: Inclusion Criteria:

• Pregnant women with pre- or early pregnancy BMI ≥ 30 kg/m2

Exclusion Criteria:

* Legal or ethical considerations: maternal age \<18 years, language difficulties requiring an interpreter or translator
* Multiple pregnancy
* Previous caesarean section
* Uncertain gestational age, defined as gestational age determined by other measurements than the Crown-Rump length (CRL) Measurement
* Planned elective caesarean section at time of randomisation
* Fetal contraindications to IOL at time of randomisation: e.g. non-cephalic presentation, or other fetal conditions contraindicating vaginal delivery
* Fetal contraindications to expectant management at time of randomisation
* Maternal contraindications to IOL at time of randomisation: e.g. placenta previa/accreta, vasa previa
* Maternal contraindications to expectant management at time of randomisation: e.g. maternal medical conditions, ultrasonically diagnosed oligohydramnios (DVP\< 2 cm), signs of labour including pre-labour rupture of membranes (PROM)

Primary outcomes:
measure: Caesarean section
timeFrame: At delivery
Secondary outcomes:
measure: Mode of delivery if not by caesarean
timeFrame: At delivery
measure: Mode of delivery
timeFrame: At delivery
measure: Vaginal assisted delivery
timeFrame: At delivery
measure: Indication for caesarean section (more than one indication is possible)
timeFrame: At delivery
measure: Indication for vaginal assisted delivery (more than one is possible)
timeFrame: At delivery
measure: Use of epidural
timeFrame: At delivery
measure: Damage to internal organs (bladder, bowel or ureters)
timeFrame: At delivery to 30 days postpartum
measure: Uterine scar dehiscense or rupture
timeFrame: At delivery
measure: Complications
timeFrame: At delivery
measure: Postpartum haemorrhage
timeFrame: 0-2 hours postpartum
measure: Hysterectomy
timeFrame: At delivery to 30 days postpartum
measure: Postpartum morbidity
timeFrame: 0-30 days postpartum
measure: Maternal admission to Intensive Care Unit
timeFrame: Enrollment to 30 days postpartum
measure: Maternal cardiopulmonary arrest
timeFrame: Enrollment to 30 days postpartum
measure: Maternal death
timeFrame: Enrollment to 30 days postpartum
measure: Primary neonatal composite including any of the following;
timeFrame: Enrollment to 28 days of life
measure: Components of the primary neonatal composite will additionally be reported separately
timeFrame: Enrollment to 28 days of life
measure: Neonatal trauma composite including any of the following;
timeFrame: At delivery to 28 days of life
measure: Neonatal asphyxia composite including any of the following;
timeFrame: At delivery to 28 days of life
measure: Apgar score at 5 minutes
timeFrame: 5 minutes of life
measure: Umbilical cord arterial and venous blood sample (allow missing data)
timeFrame: 0-30 minutes of life
measure: Neonatal admission
timeFrame: 0-72 hours of life
measure: Respiratory support during neonatal admission
timeFrame: 0-28 days of life
measure: Other treatment during neonatal admission
timeFrame: 0-28 days of life
Other outcomes:
measure: Neonatal characteristics 1
timeFrame: At delivery
measure: Neonatal characteristics 2
timeFrame: At delivery
measure: Maternal experience on birth
timeFrame: 4-6 weeks postpartum
measure: Maternal postnatal depression
timeFrame: 4-6 weeks postpartum
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Herning
country: Denmark
facility: Gødstrup Regional Hospital
city: Hillerød
country: Denmark
facility: North Zealand's Hospital
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
city: Kolding
country: Denmark
facility: Kolding Hospital
city: København
country: Denmark
facility: Rigshospitalet Juliane Marie Centre
city: Nykøbing Falster
country: Denmark
facility: Nykøbing Falster Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Randers
country: Denmark
facility: Randers Regional Hospital
city: Roskilde
country: Denmark
facility: Zealand University Hospital
city: Viborg
country: Denmark
facility: Viborg Hospital
Study officials:
affiliation: Aarhus University Hospital
name: Lise Q Krogh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Aarhus University Hospital
name: Julie Glavind, MD, PhD
role: STUDY_CHAIR
affiliation: Randers Regional Hospital
name: Sidsel Boie, MD, PhD
role: STUDY_CHAIR
affiliation: Aarhus University Hospital
name: Jens Fuglsang, MD, PhD
role: STUDY_CHAIR
affiliation: Aarhus University Hospital
name: Tine B Henriksen, MD, PhD
role: STUDY_CHAIR
affiliation: Nottingham University
name: Jim Thornton, MD, PhD
role: STUDY_CHAIR
affiliation: Aarhus University Hospital
name: Katja A Taastrøm, Midwife, MSc
role: STUDY_CHAIR
affiliation: Aarhus University Hospital
name: Anne Cathrine M Kjeldsen, Midwife, MSc
role: STUDY_CHAIR
References:
citation: Krogh LQ, Boie S, Henriksen TB, Thornton J, Fuglsang J, Glavind J. Induction of labour at 39 weeks versus expectant management in low-risk obese women: study protocol for a randomised controlled study. BMJ Open. 2022 Apr 25;12(4):e057688. doi: 10.1136/bmjopen-2021-057688.