Pessary Versus Progesterone in Singletons (AP-Singletons)
Palabras clave
Abstracto
Descripción
This open label, multi-center, randomized controlled trial aims to compare the effectiveness of cervical pessary to vaginal progesterone for prevention of PTB in women with singleton pregnancies and a cervix ≤25 mm.
All women at 16 0/7 to 22 0/7 weeks with singleton pregnancies will undergo cervical length (CL) measurement and digital examination at screening routinely. Women with a CL ≤25 mm will be eligible for the study.
Subjects meeting the study criteria will be randomized into two groups: (1) treated with cervical pessary (Arabin) or (2) treated with 200 mg vaginal progesterone, once daily.
After written informed consent, women will be randomly assigned in a 1:1 ratio to receive a cervical pessary or progesterone. Assignment to treatment allocation will be done via a web portal hosted by HOPE Research Center, Vietnam. The randomization schedule will be computer-generated at HOPE Research Center, with a permuted random block size of 2, 4 or 6. Blinding will not be possible due to the nature of interventions.
For those who randomised to pessary group, a pessary certified by European Conformity (Arabin®, Dr Arabin GmbH & Co KG, Germany) will be inserted through the vagina, upward around the cervix by 2-4 senior clinicians, who had experienced with pessary used at each site, within one week of randomization.
Women allocated to progesterone group will be receiving 200 mg vaginal progesterone, purchased from the manufacturer (Cyclogest® 200 mg, Actavis, United Kingdom), once daily at bedtime. They will be given a monitoring sheet and instructed to note everyday the date of using.
In case of premature rupture of membranes, active vaginal bleeding, other signs of preterm labor or severe patient discomfort, the pessary may be removed. If participants develop (threatened) preterm labor, they will receive treatment per local protocol. Intervention will be stopped at 370/7 weeks of gestation or at delivery.
Along side with this trial, another study will be conducted to determine how changes in peripheral blood and cervical inflammatory markers are impacted by progesterone versus pessary. Because of that, participants will be asked to take 5 ml blood sample and cervical-vaginal discharge sampling at the time of randomization, 4-8 weeks after randomization and before giving birth.
A cost-effectiveness analysis will also be conducted alongside this RCT. Data will be reported in a separated paper.
fechas
| Verificado por última vez: | 01/31/2020 |
| Primero enviado: | 02/27/2020 |
| Inscripción estimada enviada: | 03/04/2020 |
| Publicado por primera vez: | 03/08/2020 |
| Última actualización enviada: | 03/04/2020 |
| Última actualización publicada: | 03/08/2020 |
| Fecha de inicio real del estudio: | 03/04/2020 |
| Fecha estimada de finalización primaria: | 02/28/2022 |
| Fecha estimada de finalización del estudio: | 11/30/2022 |
Condición o enfermedad
Intervención / tratamiento
Device: Cervical pessary
Drug: Vaginal Progesterone
Fase
Grupos de brazos
| Brazo | Intervención / tratamiento |
|---|---|
| Active Comparator: Cervical pessary Cervical pessary (Arabin) will be inserted to participants at 16-22 weeks and removed at 37 weeks of pregnancy or in case of premature rupture of membranes, signs of preterm labour or patient severe discomfort. | Device: Cervical pessary Arabin (cervical pessary) will be inserted at 16-22 weeks and removed at 37 weeks of pregnancy or in case of premature rupture of membranes, signs of preterm labour or patient severe discomfort |
| Active Comparator: Vaginal Progesterone Vaginal progesterone (Cyclogest 200 mg) once a day will be used, from 16-22 to 37 weeks of pregnancy or in case of premature rupture of membranes, signs of preterm labour or patient severe discomfort. | Drug: Vaginal Progesterone Vaginal progesterone (Cyclogest 200 mg) once a day will be used, from 16-22 to 37 weeks of pregnancy or in case of premature rupture of membranes, signs of preterm labour or patient severe discomfort. |
Criterio de elegibilidad
| Edades elegibles para estudiar | 18 Years A 18 Years |
| Sexos elegibles para estudiar | Female |
| Acepta voluntarios saludables | si |
| Criterios | Inclusion Criteria: - Singleton pregnancies - Cervical length ≤ 25 mm, measured by TVS at the second-trimester ultrasonography (16 0/7-22 0/7 weeks of gestation) - Not participating in any other study which has intervention on maternity or fetus at the same time - Provision of written informed consent to participate as shown by a signature on the patient consent form. Exclusion Criteria: - Cervical dilation with visible amniotic membranes or amniotic membranes prolapsed into the vagina - Major congenital abnormalities of the fetus - Presence of severe vaginal discharge - Presence of vaginitis or cervicitis - Presence of vaginal bleeding - Preterm premature rupture of membranes - Premature labor without ruptured membrane at the time of screening - Suspected chorioamnionitis - Unable to have cervical pessary inserted - Cerclage or pessary in place |
Salir
Medidas de resultado primarias
1. Rate of preterm birth <37 weeks of gestation by any cause [From date of randomisation until 36 6/7 weeks]
Medidas de resultado secundarias
1. Gestational age at delivery [At birth]
2. Time from randomization to delivery [From date of randomisation until the date of delivery.]
3. Rate of preterm birth before 28 weeks of gestation [From date of randomisation until 27 6/7 weeks]
4. Rate of preterm birth before 34 weeks of gestation [From date of randomisation until 33 6/7 weeks]
5. Rate of spontaneous preterm birth <28 weeks [From date of randomisation until 27 6/7 weeks]
6. Rate of spontaneous preterm birth <34 weeks [From date of randomisation until 33 6/7 weeks]
7. Rate of spontaneous preterm birth <37 weeks [From date of randomisation until 36 6/7 weeks]
8. Rate of iatrogenic preterm birth <28 weeks [From date of randomisation until 27 6/7 weeks]
9. Rate of iatrogenic preterm birth <34 weeks [From date of randomisation until 33 6/7 weeks]
10. Rate of iatrogenic preterm birth <37 weeks [From date of randomisation until 36 6/7 weeks]
11. Rate of onset of labor [At birth]
12. Rate of modes of delivery [At birth]
13. Rate of all live births at any gestational age [At birth]
14. Rate of use of tocolytic drugs [From 24 0/7 to 36 6/7 weeks' gestation]
15. Rate of use of antenatal corticosteroids [From 24 0/7 to 36 6/7 weeks' gestation]
16. Rate of use of MgSO4 for neuroprotection [From 28 0/7 to 31 6/7 weeks' gestation]
17. Rate of preterm premature rupture of membranes [From randomization to less than 37 weeks, up to 21 weeks]
18. Length of maternal admission for preterm labor (days) [From randomization to 37 week]
19. Rate of chorioamnionitis [From randomization to delivery, up to 28 weeks]
20. Rate of maternal mortality [From randomization to delivery, up to 28 weeks]
21. Birthweight (mean) [At birth]
22. Birthweight <1500 g [At birth]
23. Birthweight <2500 g [At birth]
24. Rate of congenital anomalies [At birth]
25. 5-min Apgar score [At birth]
26. 5-min Apgar score <7 [At birth]
27. Rate of admission to neonatal intensive care unit (NICU) [Up to 28 days of life after the due day]
28. Length of NICU admission [Up to 28 days of life after the due day]
29. Rate of death before discharge [Up to 28 days of life after the due day]
30. Rate of neonatal death [Up to 28 days of life after the due day]
31. Rate of perinatal death [After 20 weeks of gestation to 28 days of life after the due day]
32. Rate of stillbirth [After 20 weeks of gestation until the date of delivery]
33. Rate of composite of poor perinatal outcomes [Up to 28 days of life after the due day]
34. Rate of respiratory distress syndrome [Up to 28 days of life after the due day]
35. Rate of periventricular haemorrhage II B or worse [Up to 28 days of life after the due day]
36. Rate of necrotizing enterocolitis [Up to 28 days of life after the due day]
37. Rate of proven sepsis [Up to 28 days of life after the due day]
38. Rate of maternal vaginal side effects [From date of randomisation until delivery, which is up to 24 weeks]
39. Vaginal pain Score [From date of randomisation until delivery, which is up to 24 weeks]
40. Rate of pessary repositioning [From date of randomisation until delivery, which is up to 24 weeks]
41. Rate of maternal cervical side effects [From date of randomisation until delivery, which is up to 24 weeks]
