Title: First trimester progesterone therapy in women with a history of unexplained recurrent miscarriages. A randomised double-blind placebo-controlled international multi-centre trial and economic evaluation.
Funder: Department of Health (England)

Abstract: 1. Women with a history of recurrent miscarriages (RM) are referred to and seen in a recurrent miscarriage clinic (standard practice) where appropriate baseline investigations are performed (standard clinical practice). If a woman fulfils the inclusion/exclusion criteria she is offered information about the PROMISE trial and invited to participate. 2. If she agrees to participate in the trial further information and instructions relating to the trial are given and written consent is obtained by the clinician or research nurse. Contact and baseline data are collected in the electronic Integrated Trial Management System. 3. The woman is given instructions to notify the research nurse by telephone as soon as she conceives (a positive urinary pregnancy test). It is expected that she will be about 4 weeks pregnant (4 weeks from last menstrual period) at this stage. When the research nurse receives the call from the woman she will obtain details about this pregnancy and recheck the womans history to ensure she is still eligible for the trial. If the woman remains eligible the nurse will randomise her to one of the two trial interventions.4. The research nurse will dispatch the trial intervention pessaries (either progesterone or placebo) to the woman within 72 hours of the telephone call via courier. 5. The woman is expected to start the trial intervention on the day it is received and continue until 12 completed weeks of gestation. In the event of the pessaries being mislaid the woman will be instructed to call the research nurse who will liaise with the trial management team to arrange a further supply of the same type of intervention. 6. The first outcome assessment (OA1-clinical pregnancy) will be an ultrasound scan performed between 6-8 weeks of gestation. An early scan at this gestational age is standard practice and routinely undertaken for women with RM attending a recurrent miscarriage clinic. If such provision is not available at the womans local hospital the research nurse will arrange for the woman to be scanned at one of the trial centres. 7. The second outcome assessment (OA2-ongoing pregnancy) will be at 12-14 weeks of gestation. This is standard practice in most RM clinics. However if it is not routinely available it will be arranged by the research nurse. 8. The third outcome assessment (OA3) is conducted after delivery to gather data on various outcomes. Prompts on the Integrated Trial Management System will alert the research nurse when each trial participant reaches her due delivery date. The local research nurse will also check birth registers and in-patient records to track hospital admissions and pregnancy outcomes. 9. The fourth and final outcome assessment (OA4) is conducted after 28 days of delivery to gather data on various outcomes. 10. At the conclusion of the trial all participants participating centres relevant patient groups and interested communities will be informed of the findings of the trial.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH