Clinical studies
Our current clinical studies, finding ways through research to improve reproductive health.
About the CASSAVA study
This research is looking at of babies and women who are in premature labour and for whom it is not known which way is the best for them to give birth: whether it is better (safer) by caesarean section (CS) or better (safer) to try and have a vaginal delivery. The first part of this research is to find out where doctors and women feel that more research on this topic is needed.
The “more research” is likely to be a randomised trial, where women who are willing to take part are allocated either to a CS or to a vaginal delivery “at random” (normally by a computer programme). We can then look at the benefits and any complications in those who have a CS and compare them with those who tried to have a vaginal delivery. Individual women and clinicians in the future can then use this information to decide which is best for them. The “at random” part is important to prevent bias, but it might reduce women’s (and clinician’s) willingness to take part in the research. Therefore, the second part of this research is to find out whether women and clinicians would be willing to take part.
COMMIT
A new global initiative set up to develop a core outcome set for future male fertility trials. Infertility affects about one in six couples, with male factor infertility causing around a third of overall cases. Core Outcome Measures for Infertility Trials (COMMIT) will be made up of clinicians, researchers and men with infertility from 25 different countries.
This multinational group will reach a global consensus to decide which outcomes should be reported and how these should be defined. These outcomes - or the ‘core outcome set’ - will be used in all future male fertility trials. This will create consistent results and a reduction of research waste. Most importantly, researchers from all over the world will be able to collect and use a set of global results and will in turn develop an increased understanding of successful treatments.
The key aim is to improve and streamline research into male infertility to enable healthcare professionals and researchers to provide better care and support for men with infertility. As well as clinicians and researchers, men with fertility problems are being encouraged to contribute, to ensure there is patient involvement and input.
DexFEM
This study builds on previous research which has provided compelling evidence that deficient activity of glucocorticoids in the endometrium is a cause of increased menstrual bleeding. This study aims to demonstrate that a glucocorticoid (dexamethasone), already in common use for other conditions, (eg to treat medical conditions such as asthma and rheumatoid arthritis in early pregnancy), will reverse the endometrial glucocorticoid deficiency and as a result reduce menstrual blood loss.
The study is in two stages, a 12 month workup stage and a 3 year, response adaptive, dose-finding randomised controlled trial. The first stage involves two workup clinical studies to gather preliminary safety and efficacy data from first-in-Heavy Menstrual Bleeding use of oral dexamethasone. They will also provide methodological data for a series of simulation studies to determine a robust adaptive trial design specification.
NIHR global health research group on preterm birth and stillbirth at the University of Edinburgh (the DIPLOMATIC collaboration)
The DIPLOMATIC Group vision is to reduce mortality of children under 5 years within 3 years, by reducing preterm birth and stillbirth and to optimise outcomes for babies born preterm. Focusing on low income countries (LIC) Malawi and Zambia, we will share existing knowledge on evidence based practices (EBP) used in high income countries (HIC) and use new trial designs to test in LIC the effectiveness of a collection of the best practices, and to evaluate how they are best implemented. A range of projects and research takes place across the University within maternal health, including those looking at the links between body mass index during pregnancy, short term morbidity and health service costs, the impact of development aid on maternal health outcomes and the biological effects of stress in utero.
GaPP2
GaPP2 is a multi-centre, double blind randomised controlled trial of the efficacy of action of gabapentin for the management of chronic pelvic pain in women. Chronic pelvic pain affects >1 million women in the UK.
The aim of GaPP2 trial is to assess whether gabapentin has the potential to provide a safe, effective and convenient oral treatment and to prove if it can alleviate pain, and improve quality of life in women with chronic pelvic pain in the absence of no obvious pelvic pathology. It also has an embedded mechanistic study using functional MRI of the brain to determine the mechanism of action of gabapentin.
GEM3
Combination Gefitinib and Methotrexate to treat ectopic pregnancies
Ectopic pregnancies are both dangerous and distressing for those experiencing them.
GEM3 is a multi-centre, double-blind, placebo-controlled randomised trial. This trial is seeking to establish whether medical treatment of ectopic pregnancy with the drug methotrexate is more effective when used in combination with the drug gefitinib. The study will be available at up to 50 centres across the UK.
Eligible patients will be offered the opportunity to be randomised to either the gefitinib or the placebo to be used in combination with the methotrexate. This involves taking one tablet a day for 7 days starting from the day the methotrexate is given, which is usually a single injection.
The study also has a mechanistic arm (Edinburgh only) which will look at the effect of gefitinib on pregnancy tissue.
GOT-IT
GOT-IT trial: A pragmatic group sequential placebo controlled randomised trial to determine the effectiveness of Glyceryl trinitrate for retained placenta.
A retained placenta (RP) is a complication after a normal birth, which affects nearly 11,000 women in the UK a year. This is where the placenta is not delivered straight away after giving birth. It is a major cause of major loss of blood (postpartum haemorrhage ) which can lead in the most serious cases to the death of the mother.
The recommended treatment for RP is a surgical procedure - manual removal of placenta (MROP). This is a painful and unpleasant procedure for the women, involving an additional stay in hospital, and is an additional cost for the NHS.
It has been recommended that research is needed into new and more acceptable medical treatments for RP. It is hoped that new effective treatments for RP would dramatically reduce the number of women requiring MROP. The reduction in MROP procedures will benefit women who will be more satisfied with their care, experience less separation from their baby immediately after birth, and will mean that women will suffer less illness associated with RP as well as having cost benefits for the NHS.
This multi-centre, placebo-controlled randomised trial will try to prove the effectiveness of a safe treatment for other conditions, called Glyceryl trinitrate (GTN) as an effective treatment for RP. We will compare GTN against a treatment which looks the same but has no active ingredients (called a placebo) in a trial where women are given one of the treatments and the results between the two groups compared to see which one works the best - this is called a randomised controlled blinded trial. The study aims to recruit up to 1100 women from 27 sites across the UK.
HEALTH: Hysterectomy or Endometrial Ablation Trial for Heavy Menstrual Bleeding
Heavy menstrual bleeding (HMB) is a very common and distressing condition which affects over 1.5 million women in the UK. Initial treatment usually involves the use of drugs, including the combined oral contraceptive pill, as well as a hormonal intrauterine contraceptive device. However, many women find these types of treatments unsuitable or unsuccessful and will need surgical treatment.
The aim of the HEALTH study is to provide information on the best surgical treatment for women with HMB in the future. The two procedures being compared are endometrial ablation and laparoscopic supra-cervical hysterectomy. These procedures will be compared in over 600 women from NHS hospitals throughout the UK to find out which one provides better relief of their symptoms.
PAPAGENO: A pragmatic approach to the prevention of gestational diabetes and pre-eclampsia in obese pregnant women in resource poor settings
A feasibility study of a randomised clinical trial of metformin (compared with matched placebo) for the prevention of diabetes and hypertensive disorders in pregnant women. This study will help to determine whether routine administration of metformin could prevent gestational diabetes and pregnancy hypertensive disorders in Malawi and Zambia. Gestational diabetes and pregnancy hypertensive disorders both cause significant maternal and neonatal deaths and long term problems, indeed pregnancy hypertensive disorders account for 17.3% of maternal deaths in low income countries, and are the second commonest cause of maternal death after haemorrhage (severe loss of blood).
PIPIN: A Feasibility Study investigating Pravastatin for the Prevention of Preterm Birth in Women
Preterm birth contributes to around 11% of all births worldwide and is the major cause of infant morbidity and mortality.
Whilst in the UK survival of babies born preterm has improved, the proportion of survivors without long term developmental problems has not, and current treatments are ineffective at preventing this. This study aims to see whether women in preterm labour would be willing to be randomised to take a tablet (pravastatin) or placebo. Preterm labour is known to be due to both inflammation within the womb and contractions. Pravastatin in an anti-inflammatory agent which has been used safely in pregnancy, and which appears in in animal studies to reduce preterm labour associated events.
We hope if women are willing to accept this trial and participate, this will help us develop a larger clinical study to find a new treatment for preterm labour.
PIPIN is currently recruiting women in preterm labour. If you would like more information, please contact Eleanor.whitaker@nhs.net
PRISM
Miscarriage is the most prevalent complication of pregnancy affecting one in five women who conceive. PRISM is a large, multi-centre, randomised, double-blind, placebo-controlled trial exploring whether progesterone, taken following the onset of vaginal bleeding within the first trimester of pregnancy until 16 weeks gestation, increases live births beyond 34 weeks.
The trial will also consider whether progesterone improves other pregnancy and neonatal outcomes or has any association with serious adverse effects to the mother or neonate. Cost-effectiveness analysis will also be performed.
PRE-EMPT
PRE-EMPT Trial is a multicentre randomised controlled trial to compare long-acting reversible contraception (LARC) versus combined oral contraceptive pill (COCP) in women where endometriosis has been confirmed at laparoscopy. Endometriosis affects 6-10% of women of reproductive age.
The trial will provide information on which treatment is the most cost effective in terms of symptom relief, side effects, acceptability and costs.
PurFECT
PurFECT (Purified Fatty acids for Endometriosis Clinical Trial) is a two-arm, parallel, randomised double-blind controlled pilot feasibility study to evaluate the efficacy of purified fatty acids in the management of endometriosis-associated pain and inform the planning of a future large multicentre trial.
The primary objective of PurFECT is to determine whether it is possible to achieve acceptable recruitment and retention rates within defined inclusion/exclusion criteria. The secondary objectives are to determine the acceptability to patients of the proposed methods of recruitment, randomisation and treatments and to obtain data to refine the research methodology for multicentre randomised control trial.
For more information please contact Dr. Ibtisam Abokhrais on 0131 242 2692 Email Ibtisam.Abokhrais@ed.ac.uk
QUIDS
Quantitative Fibronectin to help Decision-making in women with Symptoms of Preterm Labour.
Up to 80% of women who have signs and symptoms of preterm labour remain pregnant after 7 days. This means that many women unnecessarily receive therapies aimed at preventing complications in preterm babies, to ensure benefit for the few babies that are actually born preterm. The main aim of this research is to see if qfFN can accurately rule out spontaneous preterm delivery within 7 days of testing.
Through analysis of previous research data and data collected in our cohort study we will see if qfFN is likely to be a useful test – either on its own, or in combination with clinical features. We will then develop a decision support tool, to help women and clinicians assess how likely preterm delivery is, and decide whether to start treatment or not.
SLEEP EASY
Sleep disordered breathing in pregnancy: an observational study examining prevalence and potential mechanisms influencing maternal and offspring outcomes.
There is growing evidence to suggest sleep has an important role in pregnancy health. Breathing problems during sleep, known as sleep disordered breathing, have been linked to an increased risk of serious pregnancy complications including pregnancy-related diabetes (gestational diabetes), high blood pressure and delivery before 37 weeks of pregnancy. The reasons for this possible link are not well understood.
The aim of this study is to look for evidence of sleep disordered breathing in a group of 60 pregnant women, and consider how this impacts on pregnancy. Information about sleeping patterns will be gathered using overnight sleep tests and questionnaires in early and late pregnancy. Following delivery, samples of blood from the umbilical cord and placenta will be examined. Together, this information will allow us to gain a deeper understanding of how sleep disordered breathing impacts on pregnancy.
STOPPIT-2
An open randomised trial of the Arabin pessary to prevent preterm birth in twin pregnancy, with health economics and acceptability – STOPPIT-2
This study aims to determine whether the Arabin cervical pessary prevents preterm birth in women with a twin pregnancy and a short cervix. Women with a twin pregnancy are at high risk of preterm labour. The extra risk of preterm labour in twin pregnancy is the main reason why twin babies are five times more likely to die, both within the first month or the first year of life. Preterm babies who survive are at increased risk of long term disability, and often require extensive and costly health care, so if preterm birth could be prevented in twins this would be extremely beneficial.
UCON
Ulipristal acetate versus conventional management of heavy menstrual bleeding (HMB; including uterine fibroids): a randomised controlled trial and exploration of mechanism of action.
Aim of the study
Determine if Ulipristal acetate (UPA) is more effective at reducing the burden of HMB symptoms than LNG-IUS after 12 months of treatment.
Study design
A multicentre, randomised controlled trial of UPA compared to LNG-IUS with a concurrent mechanistic evaluation of UPA. 220 participants will be recruited.