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Prophylactic Administration of Natural Progesterone in the Prevention of Preterm Delivery in Twin Pregnancies

This study is currently recruiting participants.
Verified August 2011 by University of Sao Paulo
Sponsor:
Information provided by:
University of Sao Paulo
ClinicalTrials.gov Identifier:
NCT01031017
First received: December 9, 2009
Last updated: August 5, 2011
Last verified: August 2011
History of Changes
  Purpose

Twin pregnancies are at substantial increased risk of preterm delivery. Prophylactic administration of progesterone in singleton pregnancies at risk of preterm delivery has been shown to be effective in reducing the rate of such complication. The aim of this study is to investigate the effect of prophylactic administration of natural progesterone in twin pregnancies on the rate of preterm births.


Condition Intervention Phase
Preterm Delivery
 Drug: progesterone
Drug: placebo
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Prophylactic Administration of Natural Progesterone in the Prevention of Preterm Delivery in Twin Pregnancies: A Randomized, Double-Blind, Placebo-Controlled Trial

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Sao Paulo:

Primary Outcome Measures:
  • gestational age at delivery [ Time Frame: once at the end of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 380
Study Start Date: June 2007
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo
group taking placebo
 Drug: placebo
placebo
Other Name: placebo
Active Comparator: study group
group taking progesterone
 Drug: progesterone
ovules, 200mg per vagina, once a day from 18 weeks
Other Names:
  • utrogestan
  • progesterone

Detailed Description:

In a double-blind, placebo controlled study performed in our Institution, Fonseca et al., investigated the use of micronized natural progesterone, crafted in vaginal capsules of 100mg, for the prevention of preterm delivery. The study involved 142 singleton pregnancies at high risk for premature birth (previous premature birth, cerclage and uterine malformation). The progesterone was introduced from 24 weeks to 34 weeks gestation. The authors observed a significant reduction of premature birth before 37 weeks (28,1% within the placebo group versus 13,8% within the treated group) and below 34 weeks (18,6% within the placebo group versus 2,8% within the treated group). Also, it was observed a reduction in the frequency of the uterine contractions in the progesterone group.

In the only study performed specifically among twin pregnancies, Anna Lisa et al. in 1980, administrated 250mg of 17αOH-PC or placebo (still oil) weekly, in 70 pregnant women with twin pregnancies, beginning before 28 weeks and continuing up to 37 weeks gestation. Seric levels of progesterone, estradiol, estriol, testosterone, and placental lactogenic hormone were also measured weekly. The differences among the achieved results within both groups, according the average in pregnancy duration (36,9 within the treated group, versus 37,3 within the placebo group), the average birthweight and the perimortality rate were not significantly different, as well as the levels of progesterone, estriol, estradiol, testosterone and placental lactogenic hormone. Nevertheless, this study was criticized for starting the use of progesterone at a late stage of pregnancy, in a considerable number of cases.

These studies suggest that in singleton pregnancies with a previous history of preterm birth progesterone treatment may prevent the patients from having subsequent premature births. Nonetheless, the results of these series must not be generalized to all pregnancies at high risk. Additional studies to evaluate the use of progesterone ovules in multiple pregnancies are necessary, as these pregnancies are increasing due to the advanced maternal age at the conception time and also due to the widespread use of assisted reproductive techniques.

  Eligibility

Ages Eligible for Study:   15 Years to 50 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Naturally conceived diamniotic twin pregnancies.
  • Absence of major fetal abnormalities (such as neural tube defects, abdominal wall defects, cardiac defects, hydrocephalus, malformations that course with polyhydramnios) at the anomaly scan.
  • Gestational age between 18 - 21+6weeks at the moment of randomization.
  • Patients that are not allergic to the progesterone capsule excipients (arachis oil, soy and lecithin).
  • Patients who do not use other medicines that can alter the progesterone effects, such as: barbituric, carbamazepine, hydantoin, rifampicin, betablockers, teofiline or ciclosporin.
  • Porphyria, otoscleroses, malignant disease or severe depressive state.

Exclusion Criteria:

  • Premature rupture of membranes diagnosed at the moment of recruitment.
  • Subsequent diagnosis of major fetal abnormalities.
  • Twin to twin transfusion syndrome diagnosed during the course of the pregnancy.
  • Presence of ovular infection.
  • Death of one or both fetuses in any time of the pregnancy.
  • Giving up or discontinuing the use of the medication.
  • Elective or iatrogenic premature birth (before 34 weeks).
  • Present or past history of thromboembolic disease
  • Uterine malformation
  • Known or suspected breast or genitals malignancy tumor
  • Plan to move to another city during pregnancy
  • Placenta Previa
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01031017

Contacts
Contact: Maria Brizot, PhD +55 11 3069 6209 mlbrizot@uol.com.br
Contact: Adolfo Liao, PhD +55 11 3069 6209 adolfo.liao@gmail.com

Locations
Brazil
Hospital das Clinicas Recruiting
São Paulo, SP, Brazil, 05403000
Contact: Maria Brizot, PhD     +55 11 3069 6209     mlbrizot@uol.com.br    
Sponsors and Collaborators
University of Sao Paulo
Investigators
Principal Investigator: Maria Brizot, PhD Department of Obstetrics, São Paulo University Medical School
  More Information

No publications provided

Responsible Party: Maria de Lourdes Brizot, PhD, Department of Obstetrics and Gynecology, São Paulo University Medical School
ClinicalTrials.gov Identifier: NCT01031017     History of Changes
Other Study ID Numbers: 418/04
Study First Received: December 9, 2009
Last Updated: August 5, 2011
Health Authority: Brazil: National Committee of Ethics in Research

Keywords provided by University of Sao Paulo:
twin pregnancies
preterm delivery
progesterone

Additional relevant MeSH terms:
Premature Birth
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications
Progesterone
 Progestins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 17, 2013