Does progesterone prophylaxis to prevent preterm labour improve outcome?: a randomised, double-blind, placebo-controlled trial
| ISRCTN | ISRCTN14568373 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14568373 |
| Secondary identifying numbers | MRC ref: G0700452 |
- Submission date
- 29/08/2008
- Registration date
- 21/11/2008
- Last edited
- 28/06/2018
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Pregnancy and Childbirth
Plain English Summary
Background and study aims
A preterm birth is a birth that takes place more than three weeks before the baby is due (i.e., a birth before the start of the 37th week of pregnancy). There is now good evidence that the hormone progesterone prevents preterm birth in women at high risk. However, there is no evidence that preventing preterm birth with progesterone has any long-term beneficial effect on the baby. Given that we know that preterm birth is associated with intrauterine infection (infection within the womb) and inflammation, which itself is associated with brain damage for the newborn, it is possible that keeping the baby “in utero” (in the womb) when it would otherwise have been born preterm is harmful. The purpose of this study is to see if progesterone is beneficial to babies - we think it will be but this study is needed to check. The aim is to determine whether progesterone improves outcomes in women at high risk of preterm delivery. The outcomes we are interested in are those of women at delivery and babies from birth to the age of two.
Who can participate?
Women with risk factors for preterm birth (e.g., history of previous preterm birth).
What does the study involve?
Women with risk factors for preterm birth are invited to have a fetal fibronectin test (a test for detecting premature labor). All those with a positive test result and women with selected risk factors but a negative test results are then randomly allocated to be treated with either progesterone or a placebo (dummy) treatment. Participants are followed up until after delivery, and their babies are followed up until the age of 2 years. Those just screened but not treated are also followed up until delivery.
What are the possible benefits and risks of participating?
Not provided at time of registration.
Where is the study run from?
University of Edinburgh (UK).
When is the study starting and how long is it expected to run for?
October 2008 to December 2015.
Who is funding the study?
Medical Research Council (UK).
Who is the main contact?
1. Sonia Whyte (Sonia.Whyte@ed.ac.uk)
2. Lorraine Adamson (L.D.Adamson@ed.ac.uk)
Contact information
Scientific
Chair of Maternal and Foetal Health
University of Edinburgh
Centre for Reproductive Biology
The Queens Medical Research Institute
47 Little France Crescent
Edinburgh
EH16 4TJ
United Kingdom
 ORCID ID |
0000-0001-6031-6953 |
|---|---|
| Phone | +44 (0)131 242 2694 |
| jane.norman@ed.ac.uk |
Study information
| Study design | Randomised double-blind placebo-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | Patient information sheet can be found at: http://www.opptimum.org.uk/general-information.aspx |
| Scientific title | Does progesterone prophylaxis to prevent preterm labour improve outcome?: a randomised, double-blind, placebo-controlled trial |
| Study acronym | OPPTIMUM |
| Study hypothesis | Primary objective: In women at high risk of preterm labour, does prophylactic vaginal natural progesterone, 200 mg daily from 22-34 weeks gestation, compared to placebo: 1. Improve obstetric outcome by lengthening pregnancy and thus reducing the incidence of preterm delivery (before 34 weeks gestation)? 2. Improve neonatal outcome by reducing a composite of death and major morbidity? 3. Lead to improved childhood cognitive and neurosensory outcomes at two years? 4. Represent cost effective management for women at high risk of preterm delivery? More details can be found at: http://www.mrc.ac.uk/ResearchPortfolio/Grant/Record.htm?GrantRef=G0700452&CaseId=9676 |
| Ethics approval(s) | Scotland MREC A, 19/02/2008, ref: 08/MRE00/6 |
| Condition | Preterm labour |
| Intervention | Prophylactic vaginal natural progesterone, 200 mg daily from 22-24 weeks gestation until 34 weeks gestation vs placebo. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Progesterone |
| Primary outcome measure | 1. Primary obstetric outcome of the treatment phase is delivery <34 weeks of gestation (Yes/No) 2. Primary neonatal outcome is a composite of death or two markers of neonatal morbidity 3. Primary childhood outcome is developmental status at two years 4. Formal economic evaluation |
| Secondary outcome measures | 1. Gestational age at delivery 2. Death after trial entry or severe disability at two years of age 3. Incidence of the individual components of the primary neonatal outcome 4. Incidence of other major neonatal complications: need for and duration of respiratory support, surfactant administration, duration of oxygen therapy, necrotising enterocolitis, number of discrete episodes of infection (e.g., positive blood culture, cerebrospinal fluid [CSF] culture), daily level of care 5. Composite outcome of death or neurodevelopmental impairment at two years of age, the latter defined as one or more of: 5.1. Disabling cerebral palsy, defined as a score of 2 or higher on the Gross Motor Function Classification System, or 3 or higher on the Manual Ability Classification System, plus classified using the SCPE system 5.2. Developmental impairment (Cognitive standardised score <70) 5.3. Severe visual loss (legally certifiable as blind or partially sighted) 5.4. Profound/severe deafness (requiring hearing aids). Disability will be classified into domains according to professional consensus. 5.5. Brief Infant Toddler Social Emotional Assessment (BITSEA) 5.6. Women's perceptions of treatment 5.7. Maternal and child adverse events (e.g., operative delivery) |
| Overall study start date | 01/10/2008 |
| Overall study end date | 31/12/2015 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target number of participants | Planned sample size (randomised): 1125 |
| Participant inclusion criteria | Screening Study: High risk for preterm birth as indicated by at least one of the following: 1. History of previous preterm birth (PTB)/second trimester loss 2. Previous preterm premature rupture of the foetal membranes 3. Short cervical length (<25 mm) on ultrasound at 18-22 weeks gestation 4. All women will have gestation established by scan at ¡Ü 16 weeks to ensure that the estimated date of delivery is accurate 5. Signed consent form Main Study: All women fulfilling the above inclusion criteria and who have a positive screening (fFN) test at 22 weeks will be eligible for the main (treatment) phase of the study. Further consent must be obtained. |
| Participant exclusion criteria | 1. Known significant structural or chromosomal foetal anomaly 2. Known sensitivity, contraindication or intolerance to progesterone (including peanut allergy) 3. Suspected or proven rupture of the foetal membranes at the time of recruitment 4. Multiple pregnancy 5. Prescription or ingestion of medications known to interact with progesterone (e.g., ketoconazole and ciclosporin) |
| Recruitment start date | 03/12/2008 |
| Recruitment end date | 31/03/2013 |
Locations
Countries of recruitment
- Sweden
- United Kingdom
Study participating centre
United Kingdom
Sponsor information
University/education
Edinburgh Clinical Trials Unit
The Queen's Medical Research Institute
47 Little France Crescent
Edinburgh
EH16 4TJ
Scotland
United Kingdom
| Phone | +44 (0)131 242 9461 |
|---|---|
| researchgovernance@ed.ac.uk | |
| Website | http://www.ed.ac.uk |
"ROR" |
https://ror.org/01nrxwf90 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- Medical Research Council (United Kingdom), UK Medical Research Council, MRC
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | To be confirmed at a later date Participant level data may be available on request from the CI (Jane Norman) after publication of papers arising from the study |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | questionnaire results | 01/08/2010 | Yes | No | |
| Protocol article | protocol | 06/08/2012 | Yes | No | |
| Results article | results | 21/05/2016 | Yes | No | |
| Results article | results | 01/06/2018 | Yes | No |
Editorial Notes
28/06/2018: Publication reference added.
29/02/2016: Publication reference added.
03/12/2015: The following changes were made to the trial record:
1. The target number of participants was changed from 'Screening phase: 8320; treatment phase: 750' to 'Planned sample size (randomised): 1125'
2. Sweden was added to the countries of recruitment
08/04/2013: The overall trial end date was changed from 31/01/2014 to 31/12/2015.
