Verslagen

Voortgangsverslag

Samenvatting
Dit item is dichtgeklapt
Dit item is opengeklapt

Herhaalde miskraam (HM), gedefineerd als 2 of meer miskramen, treft ongeveer 5% van de koppels die zwanger proberen te worden. Bekende oorzaken zijn chromosoom afwijkingen, baarmoeder afwijkingen, endocriene verstoringen en antifosfolipidensyndroom. Na uitgebreid onderzoek wordt in minder dan 50% van de gevallen een oorzaak voor de HM gevonden. Schildklier auto-immuniteit komt bij 8 - 14 % van de vrouwen in de vruchtbare leeftijd voor. Zogenaamde TPO-antistoffen zijn aanwezig, maar de schildklier functioneert normaal. Hiervan is bekend dat dit een verhoogde kans geeft op subfertiliteit, miskraam, herhaalde miskraam, vroeggeboorte en een ontsteking van de schildklier na de bevalling. Het is onduidelijk of de toediening van schildklierhormoon tabletten de kans op een van deze complicaties verlaagt. In het belang van vrouwen met herhaalde miskraam en schildklier auto-immuniteit zal worden onderzocht of toediening van levothyroxine, het schildklierhormoon, zinvol of overbodig is en of het eventueel risico's met zich meebrengt.

Resultaten
Dit item is dichtgeklapt
Dit item is opengeklapt

De studie loopt momenteel in 15 Nederlandse ziekenhuizen en in twee buitenlandse centra (Brussel en Kopenhagen). Binnenkort zal de studie tevens van start gaan in twee Nederlandse centra en mogelijk twee buitenlandse centra. Verder bestaat de mogelijkheid voor deelname door eenmalige verwijzing vanuit andere ziekenhuizen. Er zijn op dit moment 125 patiënten geincludeerd, 52% van het benodigde aantal.

Samenvatting van de aanvraag

Samenvatting
Dit item is dichtgeklapt
Dit item is opengeklapt

BACKGROUND

Thyroid peroxidase antibodies (TPO-Ab) are present in 8-14 % of fertile women. Thyroid autoimmunity is defined as the presence of thyroid antibodies in euthyroid women. This is strongly associated with recurrent miscarriage (RM) and other pregnancy complications like preterm birth and postpartum thyroiditis. Women with recurrent miscarriage have a higher prevalence of thyroid autoimmunity, varying from 20 till 36%. Until now no randomized controlled trial has demonstrated an effective intervention in women with recurrent miscarriage and thyroid autoimmunity (TAI). There is a wide variation in clinical practice in Europe relating to the treatment and screening of thyroid autoimmunity in the work-up for recurrent miscarriage. Sometimes endocrinologists already prescribe levothyroxine to women who intend to become pregnant with thyroid antibodies and a normal thyroid function despite a lack of evidence in terms of pregnancy outcome. Considering the high prevalence of both thyroid antibodies and recurrent miscarriage this could lead to a substantial appeal to the health care system in spite of lack of evidence. Therefore, we will perform a randomized double blind placebo controlled clinical trial to assess the efficacy of thyroid hormone supplementation, as compared with placebo, on the live birth rate (LBR) and on adverse pregnancy complications in women with at least 2 preceding miscarriages and thyroid autoimmunity.

 

OBJECTIVE

First objective: To assess improvement in live birth rate and pregnancy outcome after levothyroxine treatment.

Secondary objective: to test the hypothesis that levothyroxine lowers the risk for miscarriage, or any other maternal or neonatal pregnancy complications, especially preterm birth, when compared to placebo.

 

STUDY DESIGN

Randomised double blind placebo controlled multi centre clinical trial.

 

STUDY POPULATION

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.

 

INTERVENTIONS

The intervention group receives levothyroxine (T4) , and the control group receives placebo of identical appearance.

 

MAIN STUDY PARAMETERS/ENDPOINTS

Primary outcome measure: live birth rate.

Secondary outcome measures: miscarriage rate, preterm birth, any maternal or neonatal adverse pregnancy outcomes.

 

SAMPLE SIZE

An increase in live birth rate from 55% to 75% (intention to treat population) is expected. 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

 

ECONOMIC EVALUATION

If levothyroxine proves to be an effective intervention, with a relative risk reduction of 44% miscarriages and of 70% preterm births and an implementation rate of 85%, the potential budget impact for this proposal is estimated to be -€1.7 million annually (range-0.8M€ to-2.5M€). The incremental cost effectiveness ratio (ICER), expressing the reduced cost of levothyroxine treatment per extra live birth, ranged between - €13.000 to -€35.000. The dominant factor in these calculations is the need for care due to preterm birth. When levothyroxine treatment would also result in better pregnancy rates the cost-effectiveness of treating these couples would clearly increase even further. If levothyroxine is not effective, a cost reduction can be achieved by preventing prescription of ineffective medication and unnecessary referral to endocrinologists.

 

IMPLEMENTATION

Relevant patient platforms have been informed about this project and we will use their websites and magazines to inform their patients about the study and its results. We will inform obstetricians, gynaecologists and endocrinologists and other practitioners on the outcomes at congresses, by publications, by professional organizations and by updating existing guidelines. Multiple centres have already agreed to join this research, which will facilitate the implementation of the results.

 

TIME SCHEDULE

The estimated study duration is 36 months. Inclusion of the patients will take 30 months. Data analysis and publication and implementation of the results will take six months.

Naar boven
Direct naar: InhoudDirect naar: NavigatieDirect naar: Onderkant website