Go to the T4-LIFE website.
To assess improvement in live birth rate and pregnancy outcome after levothyroxine supplementation in women with recurrent miscarriage and thyroid autoimmunity.
Randomised double blind placebo controlled multi centre clinical trial.
Women with recurrent miscarriage, i.e. at least 2 miscarriages, aged 18-42 years. Women will be recruited in the Netherlands (Coordinating Centre Academic Medical Centre, Amsterdam) and internationally.
The intervention group receives levothyroxine, and the control group receives placebo of identical appearance.
Primary outcome measure: live birth rate.
Secondary outcome measures: miscarriage rate, preterm birth, any maternal or neonatal adverse pregnancy outcomes.
We expect an increase in live birth rate from 55% to 75% (intention to treat population). This is based on a live birth rate from 55% in case of recurrent miscarriage and untreated thyroid autoimmunity14. A high relative risk reduction of 52% for miscarriages was shown in a recent meta analysis for women with thyroid autoimmunity treated with levothyroxine 20.
To detect a Minimally Important Difference (MID) of 20% in live birth beyond 24 weeks (from 55% to 75 %), with an alpha error rate of 5% and beta error rate of 20% (i.e. 80% power), 90 women will need to be randomised to the intervention arm, and 90 women to the control arm (180 in total. Assuming and adjusting for a worst case scenario of a loss to follow-up rate of 5%, the total number of participants required will be 200 (100 in each arm of the trial). We expect 15% in each group will have to be excluded after randomisation because of development of (sub) clinical hypothyroidism. To make sure we can account for these drop-outs we will allocate 120 patients to each group.
Dr. M. Goddijn, Academic Medical Centre
Dr. P.H. Bisschop, Academic Medical Centre
Prof.dr. E. Fliers, Academic Medical Centre
Prof. dr. J.A.M. van der Post, Academic Medical Centre
Prof. dr. B.W. Mol, Academic Medical Centre
Dr. Kuchenbecker, Isala Kliniek
Dr. H.R. Verhoeve, Onze Lieve Vrouwe Gasthuis
Dr. K.W.M. Bloemenkamp, Leids Universitair Medisch Centrum
Dr. M. van Wely, Epidemiologist, Academic Medical Centre
Fonds Nuths Ohra
Jan Dekkerstichting en dr Ludgardine Bouwmanstichting
Drs. M. van Dijk, PhD student, Academic Medical Centre
Meibergdreef 9, Location H4-240
1105 AZ Amsterdam