Condition category
Pregnancy and Childbirth
Date applied
29/08/2008
Date assigned
21/11/2008
Last edited
29/02/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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)

Trial website

http://www.opptimum.org.uk

Contact information

Type

Scientific

Primary contact

Prof Jane Norman

ORCID ID

http://orcid.org/0000-0001-6031-6953

Contact details

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
+44 (0)131 242 2694
jane.norman@ed.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

MRC ref: G0700452

Study information

Scientific title

Does progesterone prophylaxis to prevent preterm labour improve outcome?: a randomised, double-blind, placebo-controlled trial

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

Scotland MREC A, 19/02/2008, ref: 08/MRE00/6

Study design

Randomised double-blind placebo-controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Patient information sheet can be found at: http://www.opptimum.org.uk/general-information.aspx

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

Phase

Not Applicable

Drug names

Progesterone

Primary outcome measures

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 trial start date

01/10/2008

Overall trial end date

31/12/2015

Reason abandoned

Eligibility

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 type

Patient

Age group

Adult

Gender

Female

Target number of participants

Planned sample size (randomised): 1125

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

Trial participating centre

66 centres in the UK and Sweden
-

Sponsor information

Organisation

University of Edinburgh (UK)

Sponsor details

Edinburgh Clinical Trials Unit
The Queen's Medical Research Institute
47 Little France Crescent
Edinburgh
EH16 4TJ
United Kingdom
+44 (0)131 242 9461
researchgovernance@ed.ac.uk

Sponsor type

University/education

Website

http://www.ed.ac.uk

Funders

Funder type

Government

Funder name

Medical Research Council (UK) (grant ref: G0700452)

Alternative name(s)

MRC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

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

Intention to publish date

Participant level data

Available on request

Results - basic reporting

Publication summary

2010 questionnaire results in: http://www.ncbi.nlm.nih.gov/pubmed/21122602
2012 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/22866909
2016 results in: http://www.ncbi.nlm.nih.gov/pubmed/26921136

Publication citations

  1. Questionnaire results

    O'Brien ET, Quenby S, Lavender T, Women's views of high risk pregnancy under threat of preterm birth., Sex Reprod Healthc, 2010, 1, 3, 79-84, doi: 10.1016/j.srhc.2010.05.001.

  2. Protocol

    Norman JE, Shennan A, Bennett P, Thornton S, Robson S, Marlow N, Norrie J, Petrou S, Sebire N, Lavender T, Whyte S, Trial protocol OPPTIMUM-- does progesterone prophylaxis for the prevention of preterm labour improve outcome?, BMC Pregnancy Childbirth, 2012, 12, 79, doi: 10.1186/1471-2393-12-79.

  3. Results

    Norman JE, Marlow N, Messow CM, Shennan A, Bennett PR, Thornton S, Robson SC, McConnachie A, Petrou S, Sebire NJ, Lavender T, Whyte S, Norrie J; OPPTIMUM study group, Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomised, double-blind trial, Lancet, 2016, doi: 10.1016/S0140-6736(16)00350-0.

Additional files

Editorial Notes

29/02/2016: Publication reference added. On 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 On 08/04/2013 the overall trial end date was changed from 31/01/2014 to 31/12/2015.