When to INDuce for OverWeight? - a Randomised Controlled Trial (WINDOW)
Phase: NA
Conditions: Pregnancy, Obesity, Parturition
Sponsor: University of Aarhus

WINDOW RCT procotol version 1.3  
20201012 
1 
 
 
When to induce for overweight?  
– a randomised controlled trial 
 
Acronym: WINDOW 
 
TRIAL PROTOCOL 
 
Version: 1.3 
October 12, 2020 
 
 
ClinicalTrials.gov number: (will be filled in later) 
 
 
Trial sponsor: 
Julie Glavind, MD, PhD 
Institute for Clinical Medicine at Aarhus University Hospital 
Department of Obstetrics and Gynecology 
Palle Juul-Jensens Boulevard 99 
8200 Aarhus N 
 
 
Coordinating investigator: 
Lise Qvirin Krogh, MD, PhD-student 
Department of Obstetrics and Gynecology 
Aarhus University Hospital 
Palle Juul-Jensens Boulevard 99 
8200 Aarhus N 
Phone: +45 51242102 
Email: lise.qvirin.krogh@clin.au.dk 
 
 

WINDOW RCT procotol version 1.3  
20201012 
2 
 
 
 
 
 
 
 
 
 
Content 
Abbreviations................................................................................................................................................. 4 
Roles and responsibilities .............................................................................................................................. 5 
Trial sites ........................................................................................................................................................ 6 
Protocol amendments ................................................................................................................................... 8 
Trial registration ............................................................................................................................................ 8 
Funding .......................................................................................................................................................... 8 
1. 
Introduction ........................................................................................................................................... 9 
2. 
Objective ................................................................................................................................................ 9 
3. 
Trial design ........................................................................................................................................... 10 
4. 
Allocation ............................................................................................................................................. 10 
5. 
Intervention ......................................................................................................................................... 10 
5.1 Management strategies ..................................................................................................................... 10 
5.2 Existing pharmaceutical or non-pharmaceutical strategies .............................................................. 10 
5.3 Criteria for discontinuation ............................................................................................................... 10 
6. 
Study setting ........................................................................................................................................ 10 
7. 
Blinding ................................................................................................................................................ 11 
8. 
Eligibility criteria .................................................................................................................................. 11 
8.1 Inclusion criteria ................................................................................................................................ 11 
8.2 Exclusion criteria ................................................................................................................................ 11 
9. 
Screening for participation .................................................................................................................. 11 
9.1 The screening process ....................................................................................................................... 11 
9.2 The information process .................................................................................................................... 12 
10. 
Consent or assent ............................................................................................................................ 12 

WINDOW RCT procotol version 1.3  
20201012 
3 
 
11. 
Variables .......................................................................................................................................... 13 
11.1 Maternal demographics and pregnancy characteristics ................................................................. 13 
11.2 Neonatal characteristics .................................................................................................................. 13 
11.3 Labour characteristics ...................................................................................................................... 13 
11.4 Postpartum characteristics .............................................................................................................. 14 
11.5 Maternal experience on birth, breastfeeding and mental health ................................................... 14 
11.6 Characteristics on health resource utilization ................................................................................. 14 
11.7 Outcomes ........................................................................................................................................ 14 
11.8 Long-term follow-up ........................................................................................................................ 16 
11.9 Patients perspectives ....................................................................................................................... 16 
12. 
Harms............................................................................................................................................... 17 
12.1 General considerations .................................................................................................................... 17 
12.2 Potential harms or disadvantage ..................................................................................................... 17 
12.3 Potential benefits ............................................................................................................................ 17 
13. 
Sample size ...................................................................................................................................... 17 
14. 
Statistical analysis plan .................................................................................................................... 18 
15. 
Data collection ................................................................................................................................. 18 
15.1 Data access prior to consent ........................................................................................................... 18 
15.2 Data collection following consent ................................................................................................... 19 
16. 
Data management ........................................................................................................................... 22 
17. 
Access to data .................................................................................................................................. 22 
18. 
Monitoring ....................................................................................................................................... 22 
18.1 Data monitoring and ethics committee (DMEC) and trial steering committee (TSC) ..................... 22 
18.2 Trial monitoring ............................................................................................................................... 23 
19. 
Enrolment ........................................................................................................................................ 23 
19.1 Feasibility ......................................................................................................................................... 23 
19.2 Enrolment ........................................................................................................................................ 23 
20. 
Ethics and dissemination ................................................................................................................. 23 
20.1 Ethics................................................................................................................................................ 23 
20.2 Perspectives ..................................................................................................................................... 23 
21. 
Publication plan ............................................................................................................................... 24 
22. 
Confidentiality ................................................................................................................................. 24 
23. 
Ancillary and post-trial care ............................................................................................................. 24 
References ................................................................................................................................................... 25 

WINDOW RCT procotol version 1.3  
20201012 
4 
 
 
Abbreviations 
AROM: 
Artificial Rupture of Membranes 
BMI:  
Body Mass Index 
CI:  
Confidence Interval 
CPAP: 
Continuos Positive Airway Pressure  
CTG: 
Cardiotocografia 
CS:  
Caesarean Section 
DMEC:  
Data Monitoring and Ethics Committee 
eCRF:  
electronic Case Record Form 
eIOL:  
elective Induction of Labour 
GCP:  
Good Clinical Practice 
GDM: 
Gestational Diabetes Mellitus 
GDPR:  
General Data Protection Regulation 
NICU:  
Neonatal Intensive Care Unit 
OR:  
Odds Ratio 
RCT:  
Randomised Controlled trial 
REDCap:  
Research Electronic Data Capture 
SOP:  
Standard Operating Procedure 
TSC:  
Trial Steering Committee 
WHO:  
World Health Organisation  
 
 
 

WINDOW RCT procotol version 1.3  
20201012 
5 
 
Roles and responsibilities 
 
WINDOW study group 
Julie Glavind, MD, PhD, Consultant in Obstetrics, Aarhus University Hospital, Denmark 
Lise Qvirin Krogh, MD, PhD-student, Obstetrics and Gynecology, Aarhus University Hospital, Denmark 
Sidsel Boie, MD, PhD-student, Obstetrics and Gynecology, Regional Hospital Randers, Denmark 
Jens Fuglsang, MD, PhD, Associate Professor in Obstetrics, Aarhus University Hospital, Denmark 
Tine Brink Henriksen, MD, Professor in Pediatrics, Aarhus University Hospital, Denmark 
Jim Thornton, MD, Professor in Obstetrics and Gynecology, Nottingham University, UK  
 
Conflicts of interest 
The members of the WINDOW study group have no conflicts of interest to declare. The trial sponsor has 
no ultimate authority over any aspects of the trial design, conduct, or reporting.  
 
 

WINDOW RCT procotol version 1.3  
20201012 
6 
 
Trial sites 
Aalborg University Hospital 
Department Obstetrics and Gynecology 
Reberbansgade 15 
9000 Aalborg  
Responsible physician investigator: Anne Nødgaard Sørensen, Senior consultant, PhD 
 
Aarhus University Hospital 
Department of Obstetrics and Gynecology 
Palle Juul Jensens Boulevard 99 
8200 Aarhus N 
Responsible physician investigator: Lise Qvirin Krogh, Consultant, PhD-student 
 
Hvidovre Hospital 
Department Obstetrics and Gynecology 
Kettegård Alle 30 
2650 Hvidovre 
Responsible physician investigator: Lone Krebs, Senior Consultant, DMSc, Professor  
 
Odense University Hospital 
Department Obstetrics and Gynecology 
J. B. Winsløws Vej 4 
5000 Odense 
Responsible physician investigator: Christina Vinter, Senior Consultant, PhD 
 
Regional Hospital Herning 
Department Obstetrics and Gynecology 
Gl. Landevej 61 
7400 Herning 
Responsible physician investigator: Iben Sundtoft, Senior Consultant, Ass. Professor, PhD 
 
Regional Hospital Randers 
Department Obstetrics and Gynecology 
Skovlyvej 1 
8930 Randers NØ 
Responsible physician investigator: Pinar Bor, Senior Consultant, Ass. Professor, PhD 
 
Rigshospitalet Juliane Marie Centret 
Department of Obstetrics  
Blegdamsvej 9 
2100 København 
Responsible physician investigator: Kristina Renault, Senior Consultant, DMSc  
 
North Zealand's Hospital 
Department Obstetrics and Gynecology 
Dyrehavevej 29 
3400 Hillerød 
Responsible physician investigator: Tine Dalsgaard Clausen, Senior Consultant, PhD 
 

WINDOW RCT procotol version 1.3  
20201012 
7 
 
Herlev Hospital 
Department Obstetrics and Gynecology 
Borgmester Ib Juuls vej 1 
2730 Herlev 
Responsible physician investigator: Lene Huusom, Senior Consultant, PhD 
 
Preliminary list, more trial sites will follow. 
 

WINDOW RCT procotol version 1.3  
20201012 
8 
 
Protocol amendments 
In case of significant protocol amendments is added to the original protocol, a new version number 
will be assigned to the protocol. Simultaneously, we will add the amendments to the clinicaltrials.gov 
registration, and we will submit a supplementary protocol to the Central Denmark Region Committee 
on Biomedical Research Ethics.  
 
Trial registration 
The trial will be registered at clinicaltrials.gov using the administrative authorities of Aarhus University 
(UAarhus). 
 
Funding 
Funding for the trial is provided by the Novo Nordic Foundation (DKK 6,500,000), the Health Research 
Foundation of Central Region Denmark (DKK 512,000), and Department of Clinical Medicine, Aarhus 
University (DKK 120,000). Additional funding will be applied from private and public funds. The funding 
agencies will have no role in any of the aspects of the trial.   
 
 

WINDOW RCT procotol version 1.3  
20201012 
9 
 
1. Introduction 
The World Health Organisation [1] defines overweight as a body mass index (BMI) of ≥25 kg/m2 and 
obesity as a BMI of ≥30 kg/m2 [1]. More than 650 million adults were obese in 2016, which corresponds 
to 13% of the adult population in the world [1]. In fertile women, the prevalence of obesity is one third 
in the United States, 20% in the UK, and 12-13% in Denmark [2, 3].  
The risk of gestational complications increases with increasing BMI [2]. Obesity in pregnancy is associated 
with a number of complications including gestational diabetes, preeclampsia, fetal macrosomia, stillbirth, 
postpartum haemorrhage, neonatal death, and caesarean delivery [4-8]. Delivery by caesarean section 
further adds significant risks of wound infection or other infectious morbidity in obese women as 
compared to normal weight women [8-10]. 
The longer duration of pregnancy, the longer the pregnant woman is at risk of pregnancy complications. 
In an otherwise low-risk pregnant woman at full term (39+ weeks of gestation), it is an on-going clinical 
dilemma, whether the benefits of elective induction of labour (eIOL) and termination of the pregnancy 
will outweigh the potential harms from the induction and delivery process [11, 12]. With regard to 
delivery complications, based on data from historical cohorts, eIOL has been associated with an increased 
risk of caesarean section and instrumental delivery [11]. Therefore, expectant management has been the 
preferred clinical option.  
This interpretation has been challenged by two randomised trials [13, 14] of which the largest, the 
ARRIVE trial, with >6000 low-risk pregnant women found that eIOL at 39 gestational week was associated 
with lower caesarean delivery rates [14]. There are no randomised studies concerning timing of eIOL in 
obese women, but three observational studies found lower odds of caesarean delivery in obese women 
with eIOL as compared to awaiting labour onset [15-17]. Furthermore, guidelines such as the guideline 
on “Care of women with obesity in pregnancy” from the Royal College of Obstetricians in the UK 
advocates that the option of induction of labour should be discussed with the pregnant women [18]. 
Current practice in Denmark is to offer eIOL at 41 gestational week and 3 to 5 days to all low-risk pregnant 
women including women with BMI of ≥30 kg/m2, whereas women with BMI of ≥35 kg/m2 are offered 
eIOL at 41 gestational week and 0 days. Danish obstetrical practice differs significantly from that used in 
other parts of the world (e.g. the United States), in particular with regard to much better prenatal care, 
but also with regard to demographic factors in the obstetric population (i.e. fewer obese and multiparous 
women) and in an overall much lower caesarean delivery rate (20% vs. 30-35% in the United States). 
Results from the United States may therefore not be immediately transferable to a Danish or a 
Scandinavian setting. Hence, a randomised trial that would compare the incidence of caesarean delivery 
among obese women whose labour is induced compared with those who are managed expectantly is 
warranted. Such a randomised study will provide new and important knowledge into the area of 
induction of labour among overweight and obese women. The results will be expected to have 
international attention and to have a large impact to the increasing number of obese pregnant women 
worldwide. 
 
2. Objective 
To compare the risk of caesarean section with eIOL versus expectant management of pregnancy in 
women with a pre- or early pregnancy BMI ≥ 30.  
 
P – Pre- or early pregnancy BMI ≥ 30 kg/m2 

WINDOW RCT procotol version 1.3  
20201012 
10 
 
I – Induction of labour at 39 gestational weeks and 0 to 3 days  
C – Expectant management until induction from 41 gestational weeks 
O – Caesarean section 
 
3. Trial design  
Multicentre randomised controlled trial parallel group with an allocation ratio of 1:1. 
 
4. Allocation  
Sequence generation and concealment; Eligible women will be randomised using an Internet-based 
randomisation programme in a 1:1 ratio using permuted and random block-sizes of 2, 4, and 6. 
Stratification will be on, site. The randomisation programme will automatically transfer the entry data to 
electronic case record forms (eCRF) in REDCap.  
Implementation; The allocation sequence is pre-coded and generated from the randomisation 
programme. 
 
5. Intervention  
5.1 Management strategies  
5.1.1 Intervention arm/elective induction of labour in pregnancy at 39 gestational week and 0 to 3 days 
Induction is performed according to local policy for induction of labour (Prostaglandin E1, E2, Foley 
catheter, cervical ripening balloon catheter, artificial rupture of membranes (AROM), or oxytocin infusion 
when applicable). All medications are approved for induction of labour.  
 
5.1.2 Comparison arm/expectant management  
Waiting for spontaneous onset of labour unless a situation develops necessitating either induction of 
labour or caesarean section. All women with prolonged pregnancy can be offered induction of labour 
from 41 gestational weeks and 0 days in accordance to local policy.  
 
5.2 Existing pharmaceutical or non-pharmaceutical strategies 
Any existing pharmaceutical or non-pharmaceutical strategies used for emotional support, labour 
support, or for pain relief prior to or during labour are permitted.  
 
5.3 Criteria for discontinuation  
Withdrawal of consent.  
 
6. Study setting 
Danish delivery wards with an in-house neonatal care unit.  
In each delivery site, a responsible physician investigator will be appointed. The responsible physician 
investigator will be formally educated about the trial and relevant procedures. Data on the individual 
study sites including the responsible physician investigators can be obtained from clinicaltrials.gov. 
We will initiate the study in three sites (Aarhus University Hospital, Regional Hospital of Randers and 
Regional Hospital of Herning), followed by the remaining sites when appropriate.  
 

WINDOW RCT procotol version 1.3  
20201012 
11 
 
7. Blinding 
The trial is open label. 
 
8. Eligibility criteria 
8.1 Inclusion criteria 
Pregnant women with pre- or early pregnancy BMI ≥ 30 kg/m2. 
 
Pre- or early pregnancy BMI is defined as the pre-pregnancy BMI stated in the patient’s medical record 
or the early pregnancy BMI obtained by the general practitioner in early pregnancy. 
 
8.2 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 not determined by Crown-Rump-Length  
• 
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: e.g. fetal conditions*  
• 
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).   
  
*Fetal conditions: Fetal demise, continuously abnormal or pathologic CTG, FGR or macrosomia 
diagnosed by ultrasound, or major malformations. All conditions are considered from an individual 
clinical perspective.  
**Maternal medical conditions: Insulin treated diabetes mellitus, any hypertensive disorder with blood 
pressure >140/90, cardiac disease, renal insufficiency, other medical or psychological conditions with 
indicated delivery < 41 gestational week and 0 days.  
 
9. Screening for participation   
9.1 The screening process 
There will be a three-step screening to optimise recruitment and at the same time taking the use of 
resources into consideration.  
In the first step screening, the women are screened for the inclusion criteria. Optimally, this screening 
will take place when the women are referred from the general practitioner. If this screening does not 
occur at this time of pregnancy it can take place later during pregnancy e.g. when attending the midwifery 
outpatient clinic, the ultrasound unit, or the outpatient clinic for pregnant women. The screening will be 
performed by a trained member of the local clinical team. If the woman meets the inclusion criteria, she 

WINDOW RCT procotol version 1.3  
20201012 
12 
 
will be registered in a screening log. A screening log is essential to avoid duplicate entries in the study. 
Duplicate entries can occur because a woman can be pregnant more than once during the inclusion 
period, and she can attend to more than one of the inclusions sites within the same pregnancy, and from 
one pregnancy to the next.  
In the second step screening, women listed in the screening log will be screened for exclusion criterions 
for the first time. Optimally, this screening will take placed when the women have attended the second 
routine ultrasound scanning at approximal gestational week 20. The screening will be performed by a 
trained member of the local clinical team. This screening step is performed to identify to whom it will be 
relevant to receive written information on the study.  
In the third step screening, women in the screening log will be screened for exclusion criterions for the 
second time to identify any new circumstances leading to exclusion. This screening step is performed to 
narrow the population eligible to receive verbal information. Optimally, this screening is performed as 
close to gestational week 38 as possible trying to ensure a minimum of exclusions after randomisation, 
and still leave time for securing the informed consent, the randomisation, and the planning of the 
intervention. This screening will be performed by the responsible physician investigator at each site or 
from another assigned research staff member from the local clinical team.  
 
9.2 The information process 
Written information on the trial will be sent electronically to women found eligible after the second step 
screening.  Women found eligible after the third step screening will be given verbal information on the 
trial from the responsible physician investigator or from another assigned research staff member at each 
site.  Verbal information will include information on the background of the study, inclusion criteria, 
potential risks and benefits, as well as practical aspects and purpose of the study.  
Depending on availability and safety circumstances the verbal information will be given per telephone, 
per video consultation, or at a consultation at the midwifery outpatient clinic, or outpatient clinic for 
pregnant women. The eligible women will have the opportunity to request an assessor. Between the 
verbal information and the consent request, the eligible woman will be offered time for consideration 
(an appropriate amount of time will be agreed individually allowing a minimum of 24 hours if needed), 
and further time can be requested as needed. 
Prior to the beginning of patient enrolment, and continuously throughout the enrolment period, 
members of the local clinical team, the responsible physician investigator, and other assigned research 
staff members will be formally introduced to the trial. This include information on the trials background, 
objectives, inclusion/exclusion criteria, intervention, and the procedures they are involved in.  
 
10. Consent or assent 
The responsible physician investigator takes responsibility that the eligibility criteria are fulfilled prior to 
randomisation and will also ensure to obtain the written consent. Consent from eligible participants is 
obtained by the responsible physician investigator or an appointed research staff member at 
approximately 38 weeks of gestation and no later than the time of randomisation. The consent form will 
be digital, and all signatures will be written on a smart phone, a tablet or a computer using REDCap which 
has dedicated functionalities for written consent.  
 

WINDOW RCT procotol version 1.3  
20201012 
13 
 
11. Variables 
11.1 Maternal demographics and pregnancy characteristics 
1. Age  
2. Pre- or early gestational BMI 
3. Pre- or early gestational weight 
4. Height 
5. Parity 
6. Marital or cohabitant status 
7. Occupation  
8. Level of education 
9. Smoking during pregnancy 
10. Ethnicity (Caucasian, Afro-Caribean, Asien, Oriental, more than one ethnicity, other) 
11. Conceived by Assisted Reproductive Technologies (y/n)  
12. 120 minutes value from Oral Glucose Tolerance Test (OGTT) in mmol/L - allow missing data 
13. Gestational diabetes mellitus treated by diet alone (y/n) 
 
11.2 Neonatal characteristics  
1. Birthweight (continuous; in grams) 
- 
Birthweight > 4500 grams 
2. Sex (boy/girl) 
 
11.3 Labour characteristics 
1. Gestational age at delivery 
2. Onset of labour: 
 
- Spontaneous 
- Induction 
- Casarean before spontaneous onset or induction of labour 
3. If induction of labour; Indications for induction of labour (more than one category possible):  
- Randomised to induction 
- Prolonged pregnancy,  
- Maternal request  
- Maternal or fetal complication/condition (free text) 
4. If induction of labour; Cervical dilation prior to induction of labour 
5. If induction of labour; Method of induction of labour (more than one category possible):  
- Prostaglandin tablet 
- Prostaglandin vaginal pad  
- Foley catheter  
- Cervical ripening catheter  
- Oxytocin infusion for induction  
- Artificial rupture of membranes and not augmentation of labour 
- Other (free text) 
6. If induction of labour; Time from induction of labour until delivery (days)  

WINDOW RCT procotol version 1.3  
20201012 
14 
 
7. If caesarean; urgency of caesarean 
8. If caesarean; Cervical dilation prior to caesarean section 
9. Use of CTG monitoring during active labour (intermittent or continuous)  
10. Use of oxytocin augmentation during labour (y/n) 
 
 
11.4 Postpartum characteristics 
1. Surgical removal of placenta due to retention. Time frame 0-2 hours postpartum 
2. Other puerperal complications treated in hospital (free text). Time frame 0-30 days postpartum 
3. Thromboembolic event (deep venous thrombosis or venous pulmonary embolism). Time frame 0-30 
days postpartum 
4. Acute colon pseudo obstruction. Time frame 0-30 days postpartum 
5. Surgical procedures in the puerperal period and indication. Time frame 0-30 days postpartum 
 
 
11.5 Maternal experience on birth, breastfeeding and mental health  
1. Birth experience (Childbirth Experience Questionnaire, CEQ1)[19]. Time frame 4-6 weeks postpartum 
2. Breastfeeding indicators. Time frame 4-6 weeks postpartum 
3. Mental health as assessed by Major Depression Inventory (MDI)[20] and Edinburgh Postnatal 
Depression Score [21]. Time frame 4-6 weeks postpartum 
 
 
11.6 Characteristics on health resource utilization 
1. Telephone consultations from randomisation to admission for delivery (n) 
2. Outpatient visits from randomisation to admission for delivery (n) 
3. Hospital admissions from randomisation to admission for delivery (n) 
4. Time on the delivery unit (hours) 
5. Maternal postpartum length of hospital stay (days) 
6. Neonatal length of hospital stay (days) 
7. Telephone consultations from delivery till 30 days postpartum (n) 
8. Outpatient visits from delivery till 30 days postpartum (n) 
9. Hospital admissions from delivery till 30 days postpartum (n) 
 
 
11.7 Outcomes 
The primary outcome is caesarean section (y/n). Time frame at any time from inclusion. 
Secondary outcomes will include: 
 
11.7.1 Maternal outcomes 
1. Mode of delivery if not by caesarean 
- vaginal delivery 
- vaginal assisted delivery 

WINDOW RCT procotol version 1.3  
20201012 
15 
 
2. Vaginal assisted delivery 
 - Forceps   
- Ventouse 
3. Indication for caesarean section (more than one is possible): 
- Labour dystocia 
- Fetal distress 
- Maternal request 
- Suspected macrosomia 
- Non-cephalic presentation 
- Extensive vaginal bleeding 
- Suspected uterine rupture 
- Maternal or fetal complication/condition (free text) 
- Other (free text) 
4. Indication for vaginal assisted delivery (more than one is possible): 
- Labour dystocia 
- Fetal distress 
- Maternal request 
- Other indication for assisted vaginal delivery (free text) 
5. Use of epidural (y/n) 
Complications: 
6. Minor shoulder dystocia defined as the need for McRoberts maneuver (y/n) 
7. Major shoulder dystocia defined as the need for procedures other than McRoberts maneuver (y/n) 
8. Clinical suspicion of abruption of the placenta leading to an intervention in labour (y/n) 
9. Cord prolapse (y/n) 
10. Maternal fever defined as temperature >38,2 oC / >38,0 oC with / without epidural (y/n) 
11. Perineal 3rd degree laceration (y/n) 
12. Perineal 4th degree laceration (y/n) 
13. Episiotomy (y/n) 
Postpartum morbidity: 
14. Postpartum haemorrhage in milliliters (continuous variable). Time frame 0-2 hours postpartum 
15. Blood loss >500ml. Time frame 0-2 hours postpartum 
16. Blood loss >1000ml. Time frame 0-2 hours postpartum 
17. Blood transfusion. Time frame 0-2 days postpartum 
18. Puerperal infection treated in hospital. Time frame 0-30 days postpartum 
19. Admission to Intensive Care Unit. Time frame 0-30 days postpartum 
14. Maternal death (y/n). Time frame from randomisation to 30 days postpartum  
11.7.2 Neonatal outcomes 
1. Neonatal composite including any of the following; Perinatal death (stillbirth and neonatal), the need 
for respiratory support (intubation and mechanical ventilation, oxygen, continuous positive airway 
pressure (CPAP), or high-flow nasal cannula (HNFC)) within 72 hours after birth if admitted to a 
neonatal department, Apgar score <4 at 5 minutes, hypoxic–ischemic encephalopathy (defined as 
the need for therapeutic hypothermia), seizures, infection (defined as antibiotic treatment 
continuously for 7 days minimum), birth trauma (bone fracture, Duchenne-Erbs palsy, or retinal 

WINDOW RCT procotol version 1.3  
20201012 
16 
 
hemorrhage), intracranial or subgaleal hemorrhage, or hypotension requiring vasopressor support. 
Time frame from randomisation during delivery hospitalisation  
All components of the above neonatal composite will additionally be reported separately. 
2. Neonatal trauma composite including any of the following; birth trauma (bone fracture, Duchenne-
Erbs palsy, or retinal hemorrhage), intracranial or subgaleal hemorrhage. Time frame birth during 
delivery hospitalisation  
3. Neonatal asphyxia composite including any of the following; seizures, Apgar score < 4 at 5 minutes, 
umbilical cord pH < 7.0, umbilical cord sBE < -15.0 mmol/l, or hypoxic–ischemic encephalopathy 
(defined as the need for therapeutic hypothermia). Time frame birth during delivery hospitalisation 
4. Apgar score at 5 minutes (absolute number) 
- <4 
- 4-7 
5. Umbilical cord arterial pH and standard base excess value (continuous variable) – allow data 
missing 
- pH < 7.0 
- sBE < -15.0 mmol/l 
6. Umbilical cord venous pH and standard base excess value (continuous variable) - allow data missing 
- pH < 7.0 
- sBE < -15.0 mmol/l 
7. Neonatal admission (y/n). Time frame 0-72 hours 
8. Treatment during admission. Time frame 0-28 days 
- CPAP (y/n) 
- HNFC (y/n) 
- Oxygen supplement treatment (y/n) 
- Ventilator treatment (y/n) 
- Therapeutic hypothermia (y/n) 
- Vasopressor support 
- Antibiotic treatment continuously for 7 days minimum 
 
11.8 Long-term follow-up 
A follow-up on long-term maternal and pediatric outcomes will be reported. An additional study specific 
protocol on the long-term outcomes will be sent to evaluation at the Central Denmark Region Committee 
on Biomedical Research Ethics when time for follow up is approaching. The initial consent form will 
include permission to contact the participant after the primary trial for the purpose of follow-up. The 
follow-up data will be reported separately.  
11.9 Patients perspectives 
Understanding the patient perspective is essential to support patient-centered care both in the present 
study and in potential, future implementation. Thus, an explorative qualitative study will be performed 
with the aim to investigate experiences, information needs and birthing experiences among women in 
the intervention arm. A purposive sample of app. 20 participants will be recruited from Aarhus University 
Hospital and interviewed 4 to 8 weeks post-partum by a social scientist researcher. Interviews are 
conducted at a time and place of the participant's choice and a semi-structured interview guide will be 

WINDOW RCT procotol version 1.3  
20201012 
17 
 
used. All interviews will be digitally recorded, transcribed verbatim and analyzed using thematic analysis. 
Participation is dependent on informed consent and consent can be withdrawn at any time.  
An amendment covering written participant information, consent form, and wording of the questions 
encompassed in the interview for this subgroup of participants will be submitted later to evaluation at 
the Central Denmark Region Committee on Biomedical Research Ethics. Recruitment for this sub study 
will not take place before approval from the Central Denmark Region Committee on Biomedical Research 
Ethics is obtained. 
 
12. Harms 
12.1 General considerations 
All antenatal management and all types of medicinal products used in the trial are used according to 
standard procedures and caretaking for pregnant women.  
The inherent risk of complications from carrying a child and giving birth exists regardless of the conduct 
of this trial. Any possible harm or disadvantage to the individual study participant is considered 
outweighed by the possible benefit to the increasing number of obese women who will be pregnant in 
the future. 
 
12.2 Potential harms or disadvantage 
Among potential harms and disadvantages for participants in the intervention group is that women 
undergoing eIOL might experience a longer duration of the stay at the delivery ward, may get side effects 
to medicinal products used for induction, and that the risk of failure to induce is present. Whether the 
birth experience will be influenced negatively is not known. To our knowledge this matter has not been 
fully explored among women undergoing eIOL at 39 weeks of gestational weeks, however IOL due to 
medical indication including postterm pregnancy has been reported to impact the birth experience 
negatively. 
 
12.3 Potential benefits 
Among other potential benefits for participants in the intervention group, termination of the pregnancy 
at 39 gestational weeks might reduce the risk of known gestational complications e.g. pre-eclamsia, fetal 
macrosomia, stillbirth etc. Studies have indicated that women undergoing eIOL have fever antepartum 
visits, and shorter maternal and neonatal hospital duration after delivery. 
 
13. Sample size  
Our proportion of the primary outcome in the non-intervention group was based on the caesarean 
section rate among women with a pre- or early pregnancy BMI ≥ 30 who delivered at Aarhus University 
Hospital in 2018. To demonstrate a reduction (>0%) in the caesarean section rate (assuming 25% in the 
control group as compared to 19% in the intervention group) with an alpha of 0.05 and a power of 85%, 
854 participants are needed in each group. Anticipating drop-out, the sample size is increased to 950 
participants in each group. This concludes to a total sample size of 1900 women with a pre- or early 
pregnancy BMI ≥ 30. 
 

WINDOW RCT procotol version 1.3  
20201012 
18 
 
14. Statistical analysis plan 
Data will primarily be analysed according to intention-to-treat but also per protocol. 
Basic demographic data will be presented with counts and percentages for categorical variables, mean 
and standard deviation for continuous Gaussian distributed variables, and median and interquartile 
range for continuous non-Gaussian variables.  
The primary outcome variable will be assessed by comparing the event rates in the two groups using 
a chi-square test with a p-value of 0.05. Results will be presented as absolute and relative risks 
along with 95% confidence intervals (Cl) and numbers needed to treat (if applicable). Categorical 
secondary outcomes will be assessed in the same way as the primary outcome. For continuous 
secondary outcomes we will assess differences between groups using the student's t-test or a non-
parametric Mann-Whitney U test, respectively.  
We will present time to delivery using Kaplan-Meier estimates and test the differences between the 
two groups using the log-rank test.  
 
Subgroup analyses will be undertaken for the following subgroups 
• 
BMI ≤ or ≥ 35 
• 
Parity 0 versus 1+ 
• 
No GDM versus GDM 
 
We will use STATA for data management and analyses.  
 
15. Data collection 
15.1 Data access prior to consent  
Pursuant to Danish Health Care Act (Sundhedsloven), section 1, paragraph 46, data* from all pregnant 
women meeting the inclusion criteria when referred from the general practitioner will be passed on to 
the project to clarify if the potential participant meet the inclusion and exclusion criteria. The data will 
be entered into the screening log in REDCap. For those not randomised, a specific reason for non-
inclusion/exclusion will be documented. All randomised participants will be entered into the main 
database when informed consent is obtained.  
 
 
*The following data will be accessed from the in-hospital electronical medical record aiming to clarify if 
the potential participant meet the inclusion and exclusion criteria: 
• 
Unique patient identifier (Danish Central Personal Register number) 
• 
Telephone number 
• 
Pre- or early pregnancy BMI 
• 
Age 
• 
Estimated ultrasound determined date of delivery 
• 
Information on: 
o Previous caesarean section  
o Singleton or multiple pregnancy  
o Certainty of gestational age 
o Planned elective caesarean section 

WINDOW RCT procotol version 1.3  
20201012 
19 
 
o Presentation of the foetus   
o Maternal pre-existing or gestational conditions 
o Fetal conditions  
 
And for the purpose of validating the internal strength and secure the generalisability of the study, the 
following characteristics will be collected on all the screened women not randomised.  
• 
Unique patient identifier (Danish Central Personal Register number) 
• 
Pre- or early pregnancy BMI 
• 
Age 
• 
Parity 
• 
Gestational diabetes mellitus treated by diet alone (GDM)  
• 
Planed site of delivery 
• 
Reason for exclusion/non randomisation 
 
15.2 Data collection following consent 
15.2.1 Data collection process 
The responsible physician investigator or an assigned and educated research staff member from the local 
clinical team will be responsible for data collection and entry. Except from some of the baseline data and 
data from the post-partum questionnaires, all data will be obtained from the in-hospital electronical 
medical record. 
1. Data collection methods; Data will be collected on eCRFs on which almost every response is pre-
coded. The forms are generated using REDCap. 
2. If participants discontinue or deviate from the intervention protocol, we will continue to collect data, 
unless the woman specifically state that we cannot collect or store her data.  
 
15.2.2 Characteristics and variables  
A detailed data dictionary that clearly defines all included variables will be created prior to patient 
enrolment. The data dictionary will provide the name of the variable (including the code used in the 
database), a detailed definition of the variable, categories for categorical variables, and units and ranges 
for continuous variables. Below is provided a brief overview of the included variables collected from the 
in-hospital electronical medical record, but details are reserved for the data dictionary. 
 
Baseline characteristics 
• 
Unique patient identifier (Danish Central Personal Register number) 
• 
Name 
• 
Labour date 
• 
Name of delivery site 
• 
Age 
• 
Parity 
• 
Pre- or early gestational BMI 
• 
Height 
• 
Conceived by Assisted Reproductive Technologies 
 
Neonatal clinical characteristics  

WINDOW RCT procotol version 1.3  
20201012 
20 
 
• 
Unique patient identifier (Danish Central Personal Register number) 
• 
Sex 
• 
Birthweight 
 
 
Maternal outcomes 
• 
Gestational diabetes mellitus treated by diet alone (GDM)  
• 
Gestational complications other than GDM after randomization: 
o Hypertensive disorder of pregnancy Other 
 
Labour outcomes 
• 
Gestational week and day at delivery  
• 
Onset of labour: 
o Spontaneous 
o Induction 
• 
Mode of delivery: 
o Caesarean section 
o Vaginal delivery 
o Vaginal assisted delivery 
• 
Indication for induction of labour: 
o Randomised to induction 
Prolonged pregnancy 
o Maternal request 
o Medical indication  
• 
Method of induction of labour:  
o Prostaglandin tablet 
o Prostaglandin vaginal pad 
o Foley catheter 
o Cervical ripening catheter 
o Oxytocin infusion for induction 
o Artificial rupture of membranes for induction 
• 
Time from induction of labour until delivery 
• 
Indication for for caesarean section: 
o Labour dystocia 
o Fetal distress 
o Maternal request  
o Non-cephalic presentation 
o Maternal medical complication 
o Elective 
o Other 
• 
Use of epidural 
• 
Use of CTG monitoring during active labour 
• 
Use of oxytocin augmentation during labour 
• 
Intrapartum complications:  
o Shoulder dystocia 
o Clinical suspicion of abruption of the placenta 
o Cord prolapse 
o Maternal fever 
o Perineal 3rd or 4th degree laceration 

WINDOW RCT procotol version 1.3  
20201012 
21 
 
o Episiotomy (y/n) 
• 
Postpartum and puerperal complications: 
o Postpartum haemorrhage 
o Blood transfusion 
o Surgical removal of placenta due to retention 
o Puerperal infection treated in hospital 
o Thromboembolic event 
o Acute colon pseudo obstruction 
o Admission to Intensive Care Unit 
o Other puerperal complications 
o Surgical procedures in the puerperal period and indication 
• 
Maternal death 
 
Neonatal outcomes 
• 
Perinatal death 
o Stillbirth 
o Neonatal 
• 
Apgar score at 5 minutes 
• 
Apgar score of 3 or less at 5 minutes 
• 
Umbilical cord arterial and venous ph. and base excess value 
• 
Asphyxia at delivery  
• 
Need for respiratory support within 72 hours after birth 
• 
Hypoxic–ischemic encephalopathy 
• 
Seizures 
• 
Infection: 
• 
Antibiotic treatment continuously for 7 days minimum Birth trauma: 
o Bone fracture 
o Duchenne-Erbs palsy 
o Retinal hemorrhage 
o Other 
• 
Hemorrhage: 
o Intracranial 
o Subgaleal 
• 
Hypotension requiring vasopressor support 
• 
Neonatal admission 
• 
Treatment during admission: 
o CPAP 
o Oxygen supplement treatment 
o Ventilator treatment 
o Therapeutic hypothermia 
o Antibiotic treatment continuously for 7 days minimum 
 
Health resource utilisation outcomes 
• 
Telephone consultations from randomisation to admission for delivery 
• 
Outpatient visits from randomisation to admission for delivery 
• 
Hospital admissions from randomisation to admission for delivery 
• 
Time on the delivery unit 
• 
Maternal postpartum length of hospital stay 

WINDOW RCT procotol version 1.3  
20201012 
22 
 
• 
Neonatal length of hospital stay 
• 
Telephone consultations from delivery till 30 days postpartum 
• 
Outpatient visits from delivery till 30 days postpartum 
• 
Hospital admissions from delivery till 30 days postpartum 
 
16. Data management 
All outcome data will be registered in an eCRF designed for the trial using the REDCap database Study. 
Data will be collected and managed using REDCap electronic data capture tools hosted at Aarhus 
University [22]. REDCap is a secure, web-based application designed to support data capture for research 
studies, providing 1) an intuitive interface for validated data entry; 2) audit trails for tracking data 
manipulation and export procedures; 3) automated export procedures for seamless data downloads to 
common statistical packages; and 4) procedures for importing data from external sources.  
Data will be handled according to all relevant Danish laws including the General Data Protection 
Regulation (“Databeskyttelsesforordningen”) and the Data Protection Act (“Databeskyttelsesloven”). 
The project is registered with the Central Denmark Region’s internal list of research projects. 
 
17. Access to data 
Beginning three months and ending three years after the publication of the last trial results, the final 
dataset will be publicly available in an anonymised form using i.e. Zenodo open data repository (CERN) 
or another equivalent database[23]. 
All relevant trial-related documents will be shared along with the data. Data will be available for any 
research purpose to all interested parties who have approval from an independent review committee. 
Interested parties will be able to request the data by contacting the trial sponsor. Authorship of 
publications emerging from the shared data will follow standard authorship guidelines and will include 
authors from the WINDOW study group depending on the nature of their involvement. 
 
18. Monitoring 
18.1 Data monitoring and ethics committee (DMEC) and trial steering committee (TSC) 
Three independent members will be appointed to the DMEC prior to initiation. The DMEC members are 
to safeguard the interests of trial participants, assess the safety of the intervention during the trial, and 
monitor the overall conduct of the clinical trial.  
Three independent members will be appointed to the TSC prior to initiation. The role of the TSC is to 
provide overall supervision for the trial on behalf of the WINDOW study group.  
The DMEC will review de-identified data for safety at two predetermined milestones (600 and 1300 
enrolled participants) but can – at any time – require extra reviews. The trial will continue while the 
DMEC review data. After the reviews, the DMEC will create a short report to the TSC with 
recommendations for continuation, modifications, or terminations of the trial. There will be no formal 
stopping criteria. Recommending termination will be at the discretion of the DMEC, and there will be no 
formal statistical criteria for termination due to safety. The final decision regarding potential 
modifications or termination will rest with the TSC. 

WINDOW RCT procotol version 1.3  
20201012 
23 
 
Documents describing the roles and responsibilities of the DMEC and the TSC, including the timings of 
meetings, methods of providing information to and from the DMEC and the TSC, frequency and format 
of meetings, statistical issues and relationships with other committees will be drafted. 
 
18.2 Trial monitoring 
The trial is continuously monitored by a Good Clinical Practice (GCP) certified monitor. A detailed 
monitoring plan will be developed prior to trial commencement.  
 
19.  Enrolment 
19.1 Feasibility 
At Aarhus University Hospital, 9% of all pregnant women have a pre- or early pregnancy BMI ≥ 30 (data 
first quarter of 2019). From these, approximately one third had a pre- or early pregnancy BMI ≥ 35. With 
the assumption that women from Aarhus Municipality are less overweight than the Danish average, and 
according to the national obstetrical guideline on obesity in pregnancy, we estimate the proportion of 
women with BMI ≥ 30 on a Danish national level to be 12%. From 60.000 proposed deliveries in 2019, 
7200 would be eligible based on their BMI; with further exclusion of decliners (~70 %) and ineligible 
women (~15%), we assume that 1080 women can be included per year. With respect to delays in project 
implementation as well as other challenges in project management, we expect the inclusion period to 
last 2,5 years or until 1900 pregnant women have approved participation. 
 
19.2 Enrolment  
Enrolment at each trial site will be continuously monitored by the local site collaborator and the principal 
investigator. Adequate participant enrolment will be achieved by an engaged and visible WINDOW study 
group, local trial site initiatives and various web-based initiatives.  
 
20. Ethics and dissemination 
20.1 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 are to approve the 
study. 
 
20.2 Perspectives 
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 we are 
obliged to seek knowledge 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 labour induction 
before term. The inclusion of quantitative and qualitative approaches in the study design opens for 
balanced discussions of benefits and drawbacks of induction of labour.  
 

WINDOW RCT procotol version 1.3  
20201012 
24 
 
21. Publication plan 
Positive, inconclusive as well as negative results from the study will be published. We aim at publishing 
at least three manuscripts in peer reviewed international scientific journals. Anticipated publications: 
1) Maternal and neonatal outcomes with induction of labour versus expectant management in obese 
women: A systematic review 
2) When to induce for overweight? (WINDOW RCT) 
3) Childbirth experience and mental health with term induction in obese women: Analysis from the 
WINDOW trail  
The principal investigator will draft these papers as first author, and the trial sponsor will be last 
corresponding author. Additional authorship will follow standard authorship guidelines and will 
include all members of the WINDOW study group and the representatives from the trial sites. 
Authorships of additional publications will depend on the nature of involvement. 
 
22. Confidentiality 
The investigators will preserve the confidentiality of the participants taking part in the study according 
to the Danish national legislation (The General Data Protection Regulation (GDPR) and the Data 
Protection Act).  
 
23. Ancillary and post-trial care 
Participants taking part in clinical studies in Denmark are insured during and after the trial according 
to the Act on Patient Safety in the Danish Health Care System.  
 
 
 

WINDOW RCT procotol version 1.3  
20201012 
25 
 
References 
1. WHO, Obesity and overweight. 2018. 
2. Marchi, J., et al., Risks associated with obesity in pregnancy, for the mother and baby: a systematic 
review of reviews. Obes Rev, 2015. 16(8): p. 621-38. 
3. Gynecology, D.S.o.O.a., Obesity and pregnancy. 2017. 
4. Poston, L., et al., Preconceptional and maternal obesity: epidemiology and health consequences. 
Lancet Diabetes Endocrinol, 2016. 4(12): p. 1025-1036. 
5. Leonard, S.A., et al., Risk of severe maternal morbidity in relation to prepregnancy body mass index: 
Roles of maternal co-morbidities and caesarean birth. Paediatr Perinat Epidemiol, 2019. 
6. Yao, R., B.L. Schuh, and A.B. Caughey, The risk of perinatal mortality with each week of expectant 
management in obese pregnancies. J Matern Fetal Neonatal Med, 2019. 32(3): p. 434-441. 
7. Ovesen, P., S. Rasmussen, and U. Kesmodel, Effect of prepregnancy maternal overweight and obesity 
on pregnancy outcome. Obstet Gynecol, 2011. 118(2 Pt 1): p. 305-12. 
8. Smid, M.C., et al., Maternal obesity and major intraoperative complications during cesarean delivery. 
Am J Obstet Gynecol, 2017. 216(6): p. 614.e1-614.e7. 
9. Smid, M.C., M.S. Kearney, and D.M. Stamilio, Extreme Obesity and Postcesarean Wound 
Complications in the Maternal-Fetal Medicine Unit Cesarean Registry. Am J Perinatol, 2015. 32(14): 
p. 1336-41. 
10. Stamilio, D.M. and C.M. Scifres, Extreme obesity and postcesarean maternal complications. Obstet 
Gynecol, 2014. 124(2 Pt 1): p. 227-32. 
11. Grobman, W.A. and A.B. Caughey, Elective induction of labor at 39 weeks compared with expectant 
management: a meta-analysis of cohort studies. Am J Obstet Gynecol, 2019. 221(4): p. 304-310. 
12. Walker, K.F., et al., Labour induction near term for women aged 35 or over: an economic evaluation. 
Bjog, 2017. 124(6): p. 929-934. 
13. Walker, K.F., et al., Randomized Trial of Labor Induction in Women 35 Years of Age or Older. N Engl J 
Med, 2016. 374(9): p. 813-22. 
14. Grobman, W.A., et al., Labor Induction versus Expectant Management in Low-Risk Nulliparous 
Women. N Engl J Med, 2018. 379(6): p. 513-523. 
15. Lee, V.R., et al., Term elective induction of labour and perinatal outcomes in obese women: 
retrospective cohort study. Bjog, 2016. 123(2): p. 271-8. 
16. Palatnik, A. and M.A. Kominiarek, Outcomes of Elective Induction of Labor versus Expectant 
Management among Obese Women at >/=39 Weeks. Am J Perinatol, 2019. 
17. Gibbs Pickens, C.M., et al., Term Elective Induction of Labor and Pregnancy Outcomes Among Obese 
Women and Their Offspring. Obstet Gynecol, 2018. 131(1): p. 12-22. 
18. Denison, F.C., et al., Care of Women with Obesity in Pregnancy: Green-top Guideline No. 72. Bjog, 
2019. 126(3): p. e62-e106. 
19. Dencker, A., et al., Childbirth experience questionnaire (CEQ): development and evaluation of a 
multidimensional instrument. BMC Pregnancy Childbirth, 2010. 10: p. 81. 
20. Bech, P., et al., The sensitivity and specificity of the Major Depression Inventory, using the Present 
State Examination as the index of diagnostic validity. J Affect Disord, 2001. 66(2-3): p. 159-64. 
21. Cox, J.L., J.M. Holden, and R. Sagovsky, Detection of postnatal depression. Development of the 10-
item Edinburgh Postnatal Depression Scale. Br J Psychiatry, 1987. 150: p. 782-6. 
22. Harris, P.A., et al., Research electronic data capture (REDCap)--a metadata-driven methodology and 
workflow process for providing translational research informatics support. J Biomed Inform, 2009. 
42(2): p. 377-81. 
23. Taichman, D.B., et al., Data Sharing Statements for Clinical Trials - A Requirement of the International 
Committee of Medical Journal Editors. N Engl J Med, 2017. 376(23): p. 2277-2279.