Recurrent miscarriage Pregnancy and Childbirth Habitual aborter
Conditions
Interventions
Current interventions as of 17/08/2021:
CERM A
Pre-Screening
Potential participants for the CERM trial will be identified by one of two ways:
1. Women on the Tommy’s ‘Recurrent Miscarriage’ database.
Sponsors
University Hospitals Coventry and Warwickshire NHS Trust
Eligibility
Sex/Gender
Female
Age
18 Years to 42 Years
Inclusion criteria
Inclusion criteria: Inclusion criteria - screening 1. Age > = 18 to = 5 CD138+ cells/10mm2
Exclusion criteria
Exclusion criteria: Current participant exclusion criteria as of 17/08/2021: Exclusion criteria– screening: 1. Known treatable cause(s) of RM. Participants may not have undergone tests for treatable causes of RM prior to registration. If a treatable cause for RM is identified after registration, the participant cannot be randomised. 1.1. Antiphospholipid antibody syndrome 1.2. Thyroid disease 1.3. Parental karyotypical abnormalities. 2. Known sub-septate uterus. 3. Poorly controlled diabetes (HbA1c >48 mmol/mol) 4. Allergy to doxycycline or its excipients 5. Doxycycline contraindicated 6. Antibiotics in the current menstrual cycle 7. Taking a medication that may interact with doxycycline 8. Myasthenia Gravis. 9. Systemic lupus erythematosus (SLE) 10. Immunodeficiency disorder 11. Known serious liver disease as judged by a medically qualified doctor assessing trial eligibility informed by referral letter from GP and hospital records 12. Alcohol dependency as judged by a medically qualified doctor assessing trial eligibility informed by referral letter from GP and hospital records 13. Long-term antibiotic(s) use. 14. Menstrual cycle =21 or =42 days 15. Any co-morbid disease or condition that would make the patient unsuitable for the trial as judged by a medically qualified doctor assessing trial eligibility informed by referral letter from GP and hospital records 16. Unable to give informed consent. 17. Participation in another clinical trial of an investigational medicinal product (CTIMP) within the last 90 days. 18. Breast feeding 19. Pregnancy Exclusion criteria– RCT: 1. Treatable cause(s) of RM 2. A course of antibiotics between screening registration and randomisation to RCT. If a woman has a course of antibiotics between screening registration and randomisation they will not be eligible for trial randomisation at the time but should be given the option to re-screen and have another biopsy to confirm eligibility for randomisation. 3. A delay of longer than three months between biopsy result and randomisation to RCT. If a woman was registered for screening over three months before randomisation to the RCT they will not be eligible for trial randomisation at the time but should be given the option to re-screen and have another biopsy to confirm eligibility for randomisation. 4. Known serious liver disease as judged by a medically qualified doctor assessing trial eligibility informed by referral letter from GP and hospital records 5. Taking a medication that may interact with doxycycline 6. Any co-morbid disease or condition that would make the patient unsuitable for the trial as judged by a medically qualified doctor assessing trial eligibility informed by referral letter from GP and hospital records 7. Pregnancy If a clinician has doubts about a participants’ suitability for the trial because of a long-term medical condition they should undertake a Full Blood Count (FBC) and Liver function tests (LFTs); in order for a woman to be included in the trial the following should apply and all required additional checks must be documented in the patients’ medical notes: 1. WBC >3 x10?/l 2. Neutrophils >1.5 x10?/l 3. Platelets >75 x10?/l and hemoglobin (Hb) >100 g/l 4. Bilirubin 30 g/dl Previous participant exclusion criteria: Exclusion criteria – screening 1. Treatable cause(s) of RM for example: 1.1. Antiphospholipid antibody syndrome 1.2. Thyroid disease 1.3. Parental karyotypical
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Ongoing pregnancy at 12 weeks, measured by ultrasound completed at approximately 12 weeks gestation. 2. Total live births plus ongoing pregnancies, measured by a cumulative of live births at the end of the trial as well as the total no. of ongoing pregnancies (as defined in outcome 1) at the end of the trial. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. No. of CD138+ cells in the endometrium, measured by endometrial biopsy, the first taken at registration, the second taken after the 14 day course of capsules. 2. Time to first conception is determined by calculating the difference between date of positive pregnancy test and date of first tablet taken post randomisation. 3. Anticipated time to first live birth is determined by date of first tablet taken to the date of pregnancy outcome if gestation >24weeks post randomisation. 4. Live births, the proportion of women with a live birth after 24 weeks of gestation in their first pregnancy after randomisation. 5. Pregnancy complications, in first pregnancy following randomisation lasting greater than 12 weeks gestation; second trimester miscarriage intrauterine death, preterm delivery, small for gestational age and placental abruption is determined by reviewing patient notes at pregnancy outcome. 6. Early pregnancy complications are determined by reviewing patient notes at pregnancy outcome and pregnancy review (12 weeks and 20-24 weeks gestation) 7. Type of miscarriage, biochemical, gestational sac, foetal, karyotype of miscarried tissue are determined by reviewing patients notes at pregnancy outcome. 8. A reassessment of the ability of the CD138+ cell test to detect which patients will benefit from doxycycline will be undertaken. This analysis will use on-going pregnancy and live births per patient in women excluded from randomisation by having low CD138+ cell scores. And those randomised to placebo. 9. Termination for social reasons is determined by reviewing patient notes at pregnancy outcome. | — |
Countries
England, United Kingdom, Wales
Contacts
Public ContactKimberley Stewart
Outcome results
None listed