Fibronectin is an accurate predictor for the occurrence of preterm birth among women with threatened preterm labour. In The Netherlands, at present all women below 32 weeks of gestation with threatened preterm labour are transferred to one in 10 perinatal centres, where they are treated with tocolytics and corticosteroids. The use of fibronectin might be a cost-effective strategy to prevent unnecessary treatment. The APOSTEL-1 study will assess whether testing for fibronectin is a cost-effective strategy that prevents unnecessary treatment in women with threatened preterm labour.
Multicenter randomized clinical diagnostic trial embedded in a cohort study. All patients will be tested for fibronectin and cervical length at admission. Patients with a cervical length below 10 mm will be treated with tocolysis. Those with negative fibronectin result and a cervical length between 10 – 30 mm will be randomised to tocolysis with nifedepine or to placebo. Patients with a cervical length more than 30 mm (independent of the fibronectin result) will not be treated with tocolysis. The total cohort will be followed.
Patients with symptoms of preterm labour will be invited to participate in the study.
Inclusion criteria cohort:
- Between 24 and 34 weeks of gestation
- Preterm labour in differential diagnosis
- Intact membranes
Exclusion criteria cohort:
- Previous tocolysis treatment for preterm contractions within the previous 7 days
- Cervical dilation of 4 cm or more at a previous vaginal exam
- Contra-indications tocolysis or prolongation of pregnancy, e.g.:
- Signs of intrauterine infection requiring an intervention
- Signs of fetal distress requiring an intervention
- Severe maternal disease (HELLP syndrome, eclampsia) requiring an intervention
Patients with a negative fibronectin test and a cervical length between 10 – 30 mm will be invited to participate in a double blind randomized trial between tocolytics (nifedipine) and placebo. Patients with cervical dilation of 4 cm or more and patients with contra-indications for nifedipine will be excluded from randomisation.
The primary outcome measure is number of days to delivery truncated at 7 days after study entry.
Secondary endpoints are neonatal mortality, neonatal morbidity, maternal morbidity (side effects of tocolysis), costs, and health related quality of life.
We propose a non-inferiority effectiveness trial. Based on our pilot study, we anticipate the probability on preterm birth within 7 days in the group of patients with a negative fibronectine test and a cervical length > 10 mm to be 5%. We need 220 patients (110 per arm) to assure with 80% power that the upper limit of the 95% one-sided CI for the difference in the proportion of preterm deliveries < 7 days will be within a prespecified non-inferiority boundary of 7.5%. The results of the randomised clinical trial will be analysed according to the intention to treat principle.
The trial results will be combined with data from the prognostic cohort in a model. The average costs and effects of test with fibronectin strategy will be compared using the “treat all” strategy as the reference. Strategies with cervical length measurements will also be assessed. Long term outcomes will be evaluated using modelling.
Start in 2009, duration 3 years.
Prof. dr. B.W.J. Mol, gynaecologist and clinical epidemiologist, AMC Amsterdam
Health Technology Assessment and Methodology
Prof. dr. B.W. Mol, gynaecologist and clinical epidemiologist, AMC Amsterdam
Dr. B.C. Opmeer, clinical epidemiologist, AMC Amsterdam
Dossier number: 80-82310-98-09056
Jolande Vis, arts-onderzoeker AMC.