Clinical trial NCT02225353: Efficacy Study of a Cervical Pessary Containing Progesterone for the Prevention of Preterm Delivery
Official title: A Randomized, Open-Label, Controlled, Multi-Center Study on the Efficacy of a Sustained Release Progesterone Cerclage Cervical Pessary at Doses of 6.3 g or 7.7 g for the Prevention of Preterm Birth and a Maximum Duration of 20 Weeks.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Preterm Birth
Keywords: Preterm birth
Short cervix
Cervical Pessaries
Progesterone
Lead sponsor: Grünenthal GmbH
Sponsor class: INDUSTRY
Collaborators: name: Laboratorios Andromaco S.A.
First posted: 2014-08-26
Enrollment: 271
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Assess the efficacy of 2 Cervical Pessaries containing 6.3 g and 7.7 g micronized progesterone for the prevention of preterm delivery, established through spontaneous birth before gestation weeks 32 (31 weeks and 6 days) and 34 (33 weeks and 6 days), when the pessary is inserted during weeks 16th and 24th and removed at 36 weeks and 6 days in pregnant women at high risk of premature birth.

Detailed description: Participant selection will be performed by screening the general population of pregnant women with single fetus monitored by the Hospital Healthcare Network, to investigate by serial transvaginal ultrasound performed between gestation weeks 16 (0 day to 7 days) and 24 (0 day to 7 days) those patients who have a cervical length between 10 mm and 25 mm, and/or women with a single fetus and cervical length ≥10 mm presenting one or more of the following risk factors:

1. preterm birth prior to 35 (34 weeks and 6 days) weeks of gestation;
2. premature rupture of membranes prior to 35 (34 and 6 days) weeks of gestation.

After insertion of the pessary or beginning of the administration with vaginal progesterone capsules and until 28 weeks of gestation, participants in the 3 treatment groups will be monitored every 4 weeks at the most or more often, if the site has established so as a control standard. After 28 weeks, patients should be monitored every 2 weeks.

The proportions of spontaneous preterm delivery before gestation weeks 32 and 34 will be compared between the control group and the 2 groups with the pessaries containing different doses of progesterone.

Eligibility criteria: Inclusion Criteria:

* Women with a single pregnancy and a cervical length of 10 mm - 25 mm between 16 and 24 weeks of gestation, without any previous factors.
* Women with a single pregnancy with 10 mm or more cervical length between 16 and 24 weeks of gestation, and pre-existing risk factors risk factors for preterm birth:
* Previous preterm birth before week 35.
* Previous rupture of membranes before week 35

Exclusion Criteria:

* Pregnancies with:

  * Major fetal abnormalities, such as lethal malformations or malformations requiring pre- or post-natal surgery; and fetal death before inclusion into the study.
  * History of rupture of membranes or prophylactic cerclage before study entry.
* Cervical or vaginal injuries prior to insertion of the pessary (e.g., cervical erosion secondary to trauma, infection, or carcinoma; vesicovaginal or rectovaginal fistulas).
* Unconscious, severely ill or mentally disabled patients, or under 16 years of age.
* Patients for whom use of progesterone is contraindicated.
* Patients with history of thrombosis.

Primary outcomes:
measure: Number of Participants Not Giving Birth Before Week 32 and Week 34 of Gestation
timeFrame: Up to 36 weeks of gestational age
Secondary outcomes:
measure: Number of Participants With Premature Rupture of Membranes
timeFrame: Up to 36 weeks of gestational age
measure: Anatomical Feature: Length of the Uterine Cervix
timeFrame: Up to 36 weeks of gestational age. Results are reported for all assessments from baseline through final visit, for a total of 8 visits, and for up to 36 weeks of gestational age.
measure: Anatomical Feature: Position of the Uterine Cervix
timeFrame: Up to 36 weeks of gestational age. Results are reported for all assessments from baseline through final visit, for a total of 8 visits, and for up to 36 weeks of gestational age.
measure: Acceptability and Tolerance of Use of the Cerclage Pessary
timeFrame: Up to 36 weeks of gestational age
measure: Number of Adverse Events Related With the Use of Treatment
timeFrame: Up to 36 weeks of gestational age
Other outcomes:
Locations:
city: Santiago
country: Chile
facility: Universidad de Chile, Hospital Barros Luco
city: Santiago
country: Chile
facility: Complejo Asistencial Dr. Sótero del Río (CASR)
city: Santiago
country: Chile
facility: Unidad de Alto Riesgo Obstétrico y Medicina Perinatal y en el Centro Perinatal Oriente (CERPO), Hospital Santiago Oriente, Dr. Luis Tisné Brousse
city: Santiago
country: Chile
facility: Universidad de Chile, Hospital Clínico San Borja Arriarán
Study officials:
affiliation: Grünenthal GmbH
name: Grünenthal Study Director
role: STUDY_DIRECTOR
References:
citation: Dodd JM, Crowther CA, Cincotta R, Flenady V, Robinson JS. Progesterone supplementation for preventing preterm birth: a systematic review and meta-analysis. Acta Obstet Gynecol Scand. 2005 Jun;84(6):526-33. doi: 10.1111/j.0001-6349.2005.00835.x.
citation: Berghella V. Novel developments on cervical length screening and progesterone for preventing preterm birth. BJOG. 2009 Jan;116(2):182-7. doi: 10.1111/j.1471-0528.2008.02008.x.
citation: Jayasooriya GS, Lamont RF. The use of progesterone and other progestational agents to prevent spontaneous preterm labour and preterm birth. Expert Opin Pharmacother. 2009 Apr;10(6):1007-16. doi: 10.1517/14656560902851403.
citation: Newcomer J. Pessaries for the treatment of incompetent cervix and premature delivery. Obstet Gynecol Surv. 2000 Jul;55(7):443-8. doi: 10.1097/00006254-200007000-00023.
citation: Arabin B, Halbesma JR, Vork F, Hubener M, van Eyck J. Is treatment with vaginal pessaries an option in patients with a sonographically detected short cervix? J Perinat Med. 2003;31(2):122-33. doi: 10.1515/JPM.2003.017.
citation: Goya M, Pratcorona L, Merced C, Rodo C, Valle L, Romero A, Juan M, Rodriguez A, Munoz B, Santacruz B, Bello-Munoz JC, Llurba E, Higueras T, Cabero L, Carreras E; Pesario Cervical para Evitar Prematuridad (PECEP) Trial Group. Cervical pessary in pregnant women with a short cervix (PECEP): an open-label randomised controlled trial. Lancet. 2012 May 12;379(9828):1800-6. doi: 10.1016/S0140-6736(12)60030-0. Epub 2012 Apr 3.