Condition category
Pregnancy and Childbirth
Date applied
31/10/2011
Date assigned
31/10/2011
Last edited
14/09/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://www.birmingham.ac.uk/research/activity/mds/trials/bctu/trials/womens/tablet/index.aspx

Contact information

Type

Scientific

Primary contact

Prof Arri Coomarasamy

ORCID ID

Contact details

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
+44 (0)121 627 2775
s.j.magson@bham.ac.uk

Additional identifiers

EudraCT number

2011-000719-19

ClinicalTrials.gov number

Protocol/serial number

11051

Study information

Scientific title

A randomised controlled trial of the efficacy and mechanism of levothyroxine treatment on pregnancy and neonatal outcomes in women with thyroid antibodies

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

South West C REC, 29/03/2011, ref: 11/SW/0036

Study design

Randomised interventional trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

http://www.birmingham.ac.uk/research/activity/mds/trials/bctu/trials/womens/tablet/investigators/documentation.aspx

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

Phase

Phase III

Drug names

Levothyroxine

Primary outcome measures

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 trial start date

10/10/2011

Overall trial end date

15/05/2017

Reason abandoned

Eligibility

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 type

Patient

Age group

Adult

Gender

Female

Target number of participants

Planned Sample Size: 900; UK Sample Size: 900

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

10/10/2011

Recruitment end date

22/01/2016

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Birmingham Women’s Hospital
Birmingham
B15 2TG
United Kingdom

Trial participating centre

For full list of centres please see: http://www.birmingham.ac.uk/research/activity/mds/trials/bctu/trials/womens/tablet/investigators/recruitment.aspx
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Sponsor information

Organisation

University of Birmingham (UK)

Sponsor details

Research Support Group
Aston Webb Building
Edgbaston
Birmingham
B15 2TT
United Kingdom

Sponsor type

University/education

Website

http://www.bctu.bham.ac.uk/

Funders

Funder type

Government

Funder name

Efficacy and Mechanism Evaluation Programme

Alternative name(s)

NIHR Efficacy and Mechanism Evaluation Programme, EME

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

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.