SOLVE: A trial randomising patients between a medical device (called Dilapan-S) and the standard pessary drug (Propess) to compare them in the process of cervical ripening before induction of labour
| ISRCTN | ISRCTN20131893 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN20131893 |
| EudraCT/CTIS number | 2016-004726-42 |
| ClinicalTrials.gov number | NCT03001661 |
| Secondary identifying numbers | 33330 |
- Submission date
- 31/05/2017
- Registration date
- 02/06/2017
- Last edited
- 16/06/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Pregnancy and Childbirth
Plain English Summary
Background and study aims:
Induction of labour (where labour is started artificially) is traditionally carried out with a range of different drugs or by surgery (rupturing the membranes or ‘waters’). The first step is to make the cervix (neck of the womb) open up, shorten and soften, which is called ripening. There are different methods that can be used to help ripening. These include a pessary called dinoprostone (or PROPESS) that is placed in the vagina. This provides a hormone that helps to prepare the cervix for labour. This is the standard drug given in the UK, which is effective but can have side effects. In recent years there has been more interest in using non-drug methods of ripening, as these have fewer side effects, but may not be as fast at bringing on labour as drugs. Dilapan-S is a mechanical device, known as an osmotic cervical dilator, which provides an alternative to drugs or surgery. Thin rods of an absorbent material (with no active drug present) are inserted into the neck of the womb (cervix) and, as they absorb fluid, they swell and mimic the natural process of 'ripening' (or preparing) the cervix. This initial process is important before contractions begin. Unlike drugs, Dilapan-S does not cause premature contractions that, when too frequent, may cause the baby to become distressed. The aim of this study is to look at the effectiveness of Dilapan-S compared to standard drug treatment used to induce labour.
Who can participate?
Pregnant women who require labour induction.
What does the study involve?
Women, who agree to take part in the study, are asked to sign a consent form. The person who takes consent then enters the participant details into a telephone system which allocates the participant to either the PROPESS or the DILAPAN-S group. The decision about which group each woman would go into is made by chance, rather like the toss of a coin. Information about labour is collected by the midwife and be kept confidentially. The study collects details of participant’s childbirth experience and any infections acquired whilst in hospital. Participants are also asked to fill in a short questionnaire about the labour experience. There are no further tests or hospital visits connected with this study.
What are the possible benefits and risks of participating?
Women will be offered an induction if they need one, whether they participate in the study or not. The team cannot promise the study will help the woman as an individual, but the answers obtained from this study will help improve the care provided to women requiring induction of labour in the future. There might be other methods available to induce labour at this hospital (e.g. balloon catheter), but these are not being researched in the SOLVE study. Women can experience side effects with PROPESS. The main risk is that contractions become too strong and the baby becomes distressed. This may happen for 1 in 20 women. Women may experience discomfort with the DILAPAN-S, and there may be a small risk of infection (1 in 100 000 women). There is also a rare risk of the pessary or rod(s) becoming trapped in the vagina or cervix, fragmenting on removal, or retracting in to the uterus (5 in 100 000 women). Should this happen the doctor may need to use forceps, or other intervention, to help remove them. All women taking part will be assessed by their doctor who will decide if they need to remain in hospital, whilst being induced, or are able to go home. If a participant needs to stay in hospital they will be monitored by a midwife.
Where is the study run from?
University of Birmingham (UK)
When is study starting and how long is it expected to run for?
February 2016 to December 2021 (updated 11/02/2021, previously: March 2021)
Who is funding the study?
MEDICEM International CR s.r.o (UK)
Who is the main contact?
Amanda Cotterill, a.cotterill.2@bham.ac.uk
Contact information
Public
SOLVE Trial Manager
University of Birmingham Public Health Building
Edgbaston
Birmingham
B15 2TT
United Kingdom
| Phone | +44 (0)7795 303 779 |
|---|---|
| solve@trials.bham.ac.uk |
Scientific
SOLVE Trial Manager
University of Birmingham Public Health Building
Edgbaston
Birmingham
B15 2TT
United Kingdom
| Phone | +44 (0)7795 303 779 |
|---|---|
| solve@trials.bham.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment, Drug, Device |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | ISRCTN20131893_PIS_10Feb17_V2.pdf |
| Scientific title | Randomised controlled trial on the use of synthetic osmotic cervical dilator in induction of labour in comparison to dinoprostone vaginal insert |
| Study acronym | SOLVE |
| Study hypothesis | The aim of this study is to compare cervical ripening using Dilapan-S with the standard use prostaglandin drug. |
| Ethics approval(s) | East Midlands - Leicester Central Research Ethics Committee, 15/02/2017, ref: 17/EM/0011 |
| Condition | Childbirth |
| Intervention | After all eligibility criteria have been confirmed and informed consent has been received, the participants can be randomised into the SOLVE trial. This will be as close as possible to induction of labour commencing. Participants will be randomised in a 1:1 ratio to one of two groups. Group 1: Dilapan-S® (synthetic osmotic cervical dilator device) rods are intended for single and continuous use for no more than 24 hours. In the group randomly assigned to the device (via a telephone randomisation line), the cervix is visualised with a sterile vaginal speculum and cleaned with iodine. Up to a maximum of five rods are inserted into the cervical canal under direct visualisation during a sterile speculum examination. Women with no maternal or fetal risk, and compliant with instructions for out-patient cervical ripening, can be discharged for home cervical ripening with respect to hospital clinical policy and invited for hospitalisation next morning for their removal. For the purpose of the trial, the rod(s) shall remain in place for up to 24 hours, but checked after 12 hours. If cervix remains unfavourable after the first series of dilators has been used for the 24 hour time period, this first series of rods will be extracted and a second series of dilators will be inserted to continue cervical ripening for up to an additional 24 hours. Once removed, there is no need for further follow-up of the patient, other than for SAEs. Group 2: Propess® 10mg vaginal delivery system consists of a non-biodegradable polymeric drug eluting device delivering 10mg dinoprostone (Prostaglandin E2) by slow release. In the group randomly assigned to dinoprostone (via a telephone randomisation line), one system will be administered high up into the posterior vaginal fornix using only small amounts of water soluble lubricants to aid insertion. After the vaginal delivery system has been inserted, the withdrawal tape may be cut with scissors always ensuring there is sufficient tape outside the vagina to allow removal. The woman should be recumbent for 20 minutes to 30 minutes after insertion. As dinoprostone will be released continuously over a period of 24 hours. If there has been insufficient cervical ripening by 24 hours, the same (initial) vaginal delivery system can be left in place for another 8 hours i.e. 32 hours in total, if this is local policy. Following this period the initial vaginal delivery system should be removed, and there should be a 24 hour interlude. If the 24 hour interlude has been reached without contractions starting, a second system of Propess can be administered and left in place for a further 32 hours (i.e., 24 + 8 hours) if there is still insufficient cervical ripening effect. Once removed, there is no need for further follow-up of the patient, other than for SAEs. There will be no follow-up of patients in the SOLVE Trial, as the intervention and data collection happen whilst the woman is in hospital (from induction to delivery). The only point at which follow-up may occur is if there is an SAE. In this case SARs/SAEs still present beyond 14 days post-partum must be followed up until the final outcome is determined. |
| Intervention type | Device |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | |
| Primary outcome measure | Current primary outcome measure as of 05/11/2020: Efficacy of the synthetic osmotic cervical dilator in cervical ripening, prior to Induction of Labour (IoL), in comparison to dinoprostone vaginal insert to successfully achieve vaginal delivery as recorded on the Baseline and Birth Case Report Form (CRF) for the trial. Previous primary outcome measure: Efficacy of the synthetic osmotic cervical dilator in cervical ripening, prior to Induction of Labour (IoL), in comparison to dinoprostone vaginal insert to successfully achieve vaginal delivery within 36 hours as recorded on the Baseline and Birth Case Report Form (CRF) for the trial. |
| Secondary outcome measures | Current secondary outcome measures as of 10/07/2020: Previous secondary outcome measures: 1. Response to a synthetic osmotic cervical dilator in cervical ripening, prior to IoL, in comparison to dinoprostone vaginal insert on successful vaginal delivery within 24, 36 and 48 hours as recorded on the baseline and Birth Case Report Form (CRF) for the trial 2. Response to a synthetic osmotic cervical dilator in cervical ripening, prior to IoL, in comparison to dinoprostone vaginal insert on rates of caesarean section, as recorded on the baseline and Birth Case Report Form (CRF) for the trial at the point of delivery of the fetus 3. Response to a synthetic osmotic cervical dilator in cervical ripening, prior to IoL, in comparison to dinoprostone vaginal insert on gain in Bishop Score, as recorded on the baseline and Birth Case Report Form (CRF) for the trial at the point of insertion of the device/drug (baseline) and at the point of removal of the drug/device once cervical ripening is complete (for the device this will be 12 or 24 hours, for the drug this will be 24, 32, 56 or 64 hours) 4. Response to a synthetic osmotic cervical dilator in cervical ripening, prior to IoL, in comparison to dinoprostone vaginal insert on maternal and neonatal safety as reported on the baseline and Birth Case Report Form (CRF) for the trial and the Serious Adverse Event (SAE) form, which will be monitored from baseline until discharge from hospital (or until resolution of an SAE) 5. Response to a synthetic osmotic cervical dilator in cervical ripening, prior to IoL, in comparison to dinoprostone vaginal insert on maternal satisfaction with cervical ripening as reported on the Maternal Satisfaction Questionnaire administered post-delivery and prior to hospital discharge 6. Response to a synthetic osmotic cervical dilator in cervical ripening, prior to IoL, in comparison to dinoprostone vaginal insert on fetal status after delivery as reported on the baseline and Birth Case Report Form (CRF) for the trial and the Serious Adverse Event (SAE) form, which will be monitored from baseline until discharge from hospital (or until resolution of an SAE) _____ Previous secondary outcome measures: 1. Response to a synthetic osmotic cervical dilator in cervical ripening, prior to IoL, in comparison to dinoprostone vaginal insert on successful vaginal delivery within 24 and 48 hours as recorded on the baseline and Birth Case Report Form (CRF) for the trial 2. Response to a synthetic osmotic cervical dilator in cervical ripening, prior to IoL, in comparison to dinoprostone vaginal insert on rates of caesarean section, as recorded on the baseline and Birth Case Report Form (CRF) for the trial at the point of delivery of the fetus 3. Response to a synthetic osmotic cervical dilator in cervical ripening, prior to IoL, in comparison to dinoprostone vaginal insert on gain in Bishop Score, as recorded on the baseline and Birth Case Report Form (CRF) for the trial at the point of insertion of the device/drug (baseline) and at the point of removal of the drug/device once cervical ripening is complete (for the device this will be 12 or 24 hours, for the drug this will be 24, 32, 56 or 64 hours) 4. Response to a synthetic osmotic cervical dilator in cervical ripening, prior to IoL, in comparison to dinoprostone vaginal insert on maternal and neonatal safety as reported on the baseline and Birth Case Report Form (CRF) for the trial and the Serious Adverse Event (SAE) form, which will be monitored from baseline until discharge from hospital (or until resolution of an SAE) 5. Response to a synthetic osmotic cervical dilator in cervical ripening, prior to IoL, in comparison to dinoprostone vaginal insert on maternal satisfaction with cervical ripening as reported on the Maternal Satisfaction Questionnaire administered post-delivery and prior to hospital discharge 6. Response to a synthetic osmotic cervical dilator in cervical ripening, prior to IoL, in comparison to dinoprostone vaginal insert on fetal status after delivery as reported on the baseline and Birth Case Report Form (CRF) for the trial and the Serious Adverse Event (SAE) form, which will be monitored from baseline until discharge from hospital (or until resolution of an SAE) |
| Overall study start date | 01/02/2016 |
| Overall study end date | 06/02/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 16 Years |
| Sex | Female |
| Target number of participants | Planned Sample Size: 860; UK Sample Size: 860 |
| Total final enrolment | 674 |
| Participant inclusion criteria | Current inclusion criteria as of 05/11/2020: 1. Women >16 years of age 2. Able to provide informed consent 3. Singleton pregnancy 4. Indication for IoL 5. Pregnancy ≥37.0 weeks (assessed as an agreed gestational age by ultrasound dating scan) 6. Living fetus with vertex presentation 7. Intact membranes Previous inclusion criteria: 1. Women aged 16 years and over 2. Understanding and capable to provide informed consent 3. Singleton pregnancy 4. Indication for IoL 5. Pregnancy ≥37.0 weeks (assessed as an agreed gestational age by ultrasound dating scan at 11-14 weeks) 6. Living fetus with vertex presentation 7. Intact membranes 8. Bishop Score ≤6 points |
| Participant exclusion criteria | Current exclusion criteria as of 05/11/2020: 1. Women already receiving oxytocin 2. Diagnosis of fulminant preeclampsia/eclampsia 3. Contraindication to Dinoprostone or Dilapan 4. If Dinoprostone for loL is non-compliant with local policy 5. Enrolled in other randomised controlled trials of an IMP or device for cervical ripening or induction of labour Previous exclusion criteria: 1. Contraindication for vaginal delivery (i.e., placenta previa) 2. When labour has already started (defined as regular painful contractions) 3. When oxytocin is being administered 4. Fulminant preeclampsia/eclampsia 5. Clinical signs of uterine, cervical, vaginal or vulval infection (except Group B Streptococcal colonisation) 6. Known allergy or contraindication to drug or device ingredients 7. Previous uterine body/midline/classical caesarean section (EXCEPT lower segment caesarean section) 8. More than one previous caesarean section 9. Known uterine abnormality 10. Suspected fetal hypoxia (i.e., CTG recording evaluated as abnormal prior to pre-induction initiation) 11. Unstable lie 12. Active antepartum haemorrhage at the time of induction 13. Four or more full-term deliveries 14. Known fetal anomalies |
| Recruitment start date | 30/06/2017 |
| Recruitment end date | 27/01/2021 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Birmingham
B18 7QH
United Kingdom
Birmingham
B9 5SS
United Kingdom
Edgbaston
Birmingham
B15 2TG
United Kingdom
Sponsor information
Hospital/treatment centre
Birmingham Women’s and Children’s Hospital
Mindelsohn Way
Edgbaston
Birmingham
B4 6NH
England
United Kingdom
| Phone | +44 (0)121 333 8749 |
|---|---|
| e.adey@nhs.net | |
"ROR" |
https://ror.org/056ajev02 |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 30/09/2021 |
|---|---|
| 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. |
| IPD sharing plan | The current 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 | version V2 | 10/02/2017 | 02/06/2017 | No | Yes |
| Participant information sheet | version v4.0 | 02/08/2018 | 10/07/2020 | No | Yes |
| Participant information sheet | version v3.0 | 10/10/2017 | 05/11/2020 | No | Yes |
| Basic results | 28/10/2021 | 16/06/2022 | No | No | |
| HRA research summary | 28/06/2023 | No | No |
Additional files
- ISRCTN20131893_PIS_v4.0_02Aug2018.pdf
- Uploaded 10/07/2020
- ISRCTN20131893_PIS_10Feb17_V2.pdf
- Uploaded 02/06/2017 (superseded)
- ISRCTN20131893_PIS_v3.0_10Oct17.pdf
- Uploaded 05/11/2020 (superseded)
Editorial Notes
16/06/2022: EU Clinical Trials Register results added.
09/07/2021: The following changes have been made:
1. The overall trial end date has been changed from 31/12/2021 to 06/02/2021.
2. The intention to publish date has been changed from 30/03/2022 to 30/09/2021.
11/02/2021: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/12/2020 to 27/01/2021.
2. The overall end date was changed from 31/03/2021 to 31/12/2021.
3. The intention to publish date was changed from 30/09/2021 to 30/03/2022.
4. The plain English summary was updated to reflect these changes.
5. The total final enrolment was added.
05/11/2020: The following changes were made to the trial record:
1. The primary outcome measure, sponsor contact details, inclusion and exclusion criteria were updated.
2. Princess Royal Hospital was removed as a trial participating centre.
3. An updated participant information sheet has been uploaded.
10/07/2020: The following changes have been made:
1. The overall trial end date has been changed from 31/08/2019 to 31/03/2021.
2. The secondary outcome measures have been changed.
3. The trial website has been added.
4. The participant information sheet field has been updated with instructions on how to request a sheet.
5. Princess Royal Hospital has been added to the trial participating centres.
6. The intention to publish date has been changed from 31/08/2020 to 30/09/2021.
7. The plain English summary has been updated accordingly and to change the trial contact.
8. The public contact has been changed.
9. The recruitment end date has been changed from 29/06/2019 to 31/12/2020.
10. An updated participant information sheet has been uploaded.
16/01/2020: ClinicalTrials.gov number added.
26/03/2019: The condition has been changed from "Specialty: Reproductive health and childbirth, Primary sub-specialty: General Obstetrics/ Midwifery; UKCRC code/ Disease: Reproductive Health and Childbirth/ Delivery" to "Childbirth" following a request from the NIHR.
