Thyroid AntiBodies and LEvoThyroxine study (TABLET)
| ISRCTN | ISRCTN15948785 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15948785 |
| EudraCT/CTIS number | 2011-000719-19 |
| Secondary identifying numbers | 11051 |
- Submission date
- 31/10/2011
- Registration date
- 31/10/2011
- Last edited
- 28/05/2020
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Pregnancy and Childbirth
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English Summary
Not provided at time of registration
Contact information
Prof Arri Coomarasamy
Scientific
Scientific
Professor of Gynaecology
Director, Tommy’s National Centre for Miscarriage Research
Institute of Metabolism and Systems Research
University of Birmingham, UK
Consultant Gynaecologist and Sub-specialist in Reproductive Medicine
Birmingham Women's Hospital, UK
Birmingham
B15 2TG
United Kingdom
| Phone | +44 (0)121 627 2775 |
|---|---|
| s.j.magson@bham.ac.uk |
Study information
| Study design | Randomised interventional trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | http://www.birmingham.ac.uk/research/activity/mds/trials/bctu/trials/womens/tablet/investigators/documentation.aspx |
| Scientific title | A randomised controlled trial of the efficacy and mechanism of levothyroxine treatment on pregnancy and neonatal outcomes in women with thyroid antibodies |
| Study acronym | TABLET |
| Study hypothesis | Current study hypothesis as of 29/04/2013: Levothyroxine will assist women aged 16-40 with a history of one or more miscarriage or who are being treated for infertility, who have been identified as having thyroid antibodies (TPO antibody positive) trying to conceive within 1 year of miscarriage. Previous study hypothesis until 29/04/2013: Levothyroxine will assist women aged 16-40 with a history of one or more miscarriage, who have been identified as having thyroid antibodies (TPO antibody positive) trying to conceive within 1 year of miscarriage. |
| Ethics approval(s) | South West C REC, 29/03/2011, ref: 11/SW/0036 |
| Condition | Reproductive health, childbirth |
| Intervention | Current interventions as of 29/04/2013: Women aged 16-40 with a history of one or more miscarriage or who are being treated for infertility, who have been identified as having thyroid antibodies (TPO antibody positive), and will be trying to conceive within 1 year. Prevous interventions until 29/04/2013: Women aged 16-40 with a history of one or more miscarriage, who have been identified as having thyroid antibodies (TPO antibody positive), and will be trying to conceive within 1 year of miscarriage. Levothyroxine, 50mcg Levothyroxine, overencapsulated to be taken orally daily versus placebo, to match investigational medicinal products (IMP). Followed Up at 21 month(s) |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Levothyroxine |
| Primary outcome measure | Current primary outcome measures as of 14/09/2017: Live birth at or beyond 34 weeks (greater than or equal to 34). The denominator of this proportion will be all women randomised, and the numerator will be those women who proceed to have a live birth at or beyond 34 weeks. Previous primary outcome measures: Live birth measured at beyond 34 weeks gestational age |
| Secondary outcome measures | Current secondary outcome measures as of 14/09/2017: 1. Clinical pregnancy assessed using urine test at 7 weeks 2. Ongoing pregnancy assessed using scan at 12 weeks 3. Miscarriage <24 weeks, clinical assessment 4. Stillbirth (inter-uterine death ≥24 weeks), clinical assessment 5. Ectopic pregnancy, clinical assessment 6. Termination (and reasons), clinical assessment 7. Live birth <34 weeks, clinical assessment 8. Time from conception to pregnancy end (any reason) 9. Mode of initiation of labour (spontaneous/induced) 10. Mode of delivery (vaginal/operative vaginal/caesarean) 11. Gestation at delivery, weeks (scan) 12. Time from conception to live birth 13. Gestation at delivery <28 weeks/<34 weeks/<37 weeks 14. Birth weight, grams 15. Birth weight adjusted for gestational age and sex, centiles 16. Birth weight adjusted for gestational age, sex, parity, maternal BMI and ethnicity, centiles 17. Small for gestational age and sex (birth weight proportion<10th centile) 18. Small for gestational age, sex, parity, maternal BMI and ethnicity (birth weight proportion<10th centile) 19. Large for gestational age and sex (birth weight proportion>=90th centile) 20. Large for gestational age, sex, parity, maternal BMI and ethnicity (birth weight proportion>=90th centile) 21. APGAR score, clinical assessment at 1 minute/5 minutes 22. Serum TSH concentration (mu/l; log transformed), assessed by blood test at each assessment time (3 months, 6 months, 9 months, 6-8 weeks pregnancy, 16-18 weeks pregnancy and 28 weeks pregnancy) 23. Serum free T4 level (pmol/L), assessed by blood test at each assessment time (3 months, 6 months, 9 months, 6-8 weeks pregnancy, 16-18 weeks pregnancy and 28 weeks pregnancy) 24. Maternal antenatal complications (hyperemesis gravidarum/gestational diabetes/pre-eclampsia or eclampsia/obstetric cholestasis/pre-term pre labour rupture of membranes (PPROM)/intrauterine growth restriction (IUGR)/others), clinical assessment 25. Intrapartum complications (shoulder dystocia/others), clinical assessment 26. Maternal postnatal complications (admission to HDU or ITU/Abnormal thyroid test within four weeks/referred to psychiatrist or started on antidepressants/others), clinical assessment 27. Neonatal complications (early neonatal death defined as death within 7 days after delivery/late neonatal death defined as death beyond 7 days and before 28 days post-delivery/admission to NNU/SCBU/active resuscitation within first 28 days/surfactant use/mechanical ventilation/intermittent positive pressure ventilation/continuous positive airway pressure/oxygen use/congenital abnormalities/hypoxic ischaemic encephalopathy/retinopathy of prematurity/respiratory distress syndrome/pneumothorax/intraventricular hemorrhage (grade 3 or 4)/necrotizing enterocolitis/early infection/others), clinical assessment 28. Reported symptoms that participant is concerned about at each assessment time (3 months, 6 months, 9 months, 6-8 weeks pregnancy, 16-18 weeks pregnancy and 28 weeks pregnancy) 29. Serious Adverse Events, clinical assessment at 3 months, 6 months, 9 months, 6-8 weeks pregnancy, 16-18 weeks pregnancy and 28 weeks pregnancy Previous secondary outcome measures (added 29/04/2013): 1. Gestation at delivery 2. Conception (urinary pregnancy) rate 3. Clinical pregnancy at 6 8 weeks 4. On-going pregnancy at 11-13 weeks 5. Miscarriage (delivery before 24 weeks of gestation) 6. Survival at 28 days of neonatal life 7. Thyroid function tests |
| Overall study start date | 10/10/2011 |
| Overall study end date | 15/05/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Female |
| Target number of participants | Planned Sample Size: 900; UK Sample Size: 900 |
| Total final enrolment | 952 |
| Participant inclusion criteria | Current inclusion criteria as of 29/04/2013: 1. Women trying to conceive 2. History of one or more miscarriage(s) or who are being treated for infertility 3. Age 16 40 years at randomisation 4. Biochemically euthyroid (Free T4 and TSH within specified reference ranges) 5. Thyroid Peroxidase Antibody (TPO) positive 6. Willing and able to give written informed consent Previous inclusion criteria until 29/04/2013: 1. Women trying to conceive 2. History of one or more miscarriage(s) 3. Age 16 40 years at randomisation 4. Biochemically euthyroid (Free T4 and TSH within specified reference ranges) 5. Thyroid Peroxidase Antibody (TPO) positive 6. Willing and able to give written informed consent |
| Participant exclusion criteria | Current exclusion criteria as of 29/04/2013: 1. Current or past treatment for thyroid disease 2. Contraindication to levothyroxine treatment 3. Thyrotoxicosis 4. Hypersensitivity to any components tablets 5. Women taking amiodarone or lithium therapy 6. Participants in any other blinded, placebo controlled trials on Investigational Medicinal Products in pregnancy 7. Previous or current diagnosis of cardiac disease Previous exclusion criteria until 29/04/2013: 1. Current or past treatment for thyroid disease 2. Contraindication to levothyroxine treatment 3. Thyrotoxicosis 4. Hypersensitivity to any components tablets 5. Women taking amiodarone or lithium therapy 6. Participants in any other blinded, placebo controlled trials on Investigational Medicinal Products in pregnancy 7. Planning to conceive using ovulation stimulation therapy 8. Previous or current diagnosis of cardiac disease |
| Recruitment start date | 01/11/2011 |
| Recruitment end date | 22/01/2016 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Birmingham Womens Hospital
Birmingham
B15 2TG
United Kingdom
B15 2TG
United Kingdom
For full list of centres please see: http://www.birmingham.ac.uk/research/activity/mds/trials/bctu/trials/womens/tablet/investigators/recruitment.aspx
-
United Kingdom
United Kingdom
Sponsor information
University of Birmingham (UK)
University/education
University/education
Research Support Group
Aston Webb Building
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
| Website | http://www.bctu.bham.ac.uk/ |
|---|---|
"ROR" |
https://ror.org/03angcq70 |
Funders
Funder type
Government
Efficacy and Mechanism Evaluation Programme
Government organisation / National government
Government organisation / National government
- Alternative name(s)
- NIHR Efficacy and Mechanism Evaluation Programme, EME
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/05/2018 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | 1. The protocol is available at: https://www.birmingham.ac.uk/research/activity/mds/trials/bctu/trials/womens/tablet/investigators/documentation.aspx 2. The final report will be published in May 2018 |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 04/04/2019 | Yes | No | |
| Basic results | 28/05/2020 | No | No | ||
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
28/05/2020: Added clinicaltrialsregister.eu link to basic results (scientific).
23/04/2019: The total final enrolment has been added from the results publication.
26/03/2019: Publication reference added.
28/09/2018: The recruitment start date has been changed from 10/10/2011 to 01/11/2011.
14/03/2018: IPD sharing statement added.
21/02/2018: Publication and dissemination plan updated.
14/09/2017: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/10/2015 to 22/01/2016.
2. The overall trial end date was changed from 31/10/2015 to 15/05/2017.
29/04/2013: The overall trial end date was changed from 31/12/2013 to 31/10/2015.
