Vaginal Progesterone in Twins With Short Cervix

Vaginal Progesterone to Prevent Early Preterm Birth In Twin Pregnancy With Short Cervix. Double-Blind, Placebo-Controlled, Randomized Clinical Trial

A Multicenter, Double-Blind, Placebo-Controlled Randomized Clinical Trial of Vaginal Progesterone to Prevent Early Preterm Birth In Twin Pregnancy with Short Cervix.

Study Overview

• Status: Withdrawn
• Conditions: Premature Birth
• Intervention / Treatment: Drug: Vaginal Progesterone gel.; Procedure: fetal fibronectin swab.; Drug: Placebo gel

Detailed Description

This is a placebo-controlled, double-blind, randomized clinical trial of asymptomatic women with twin pregnancy and a cervix length 10 mm to 25 mm discovered on a routine screening transvaginal sonogram between 20w0d to 24w0d gestational age. Women will be randomized in either the in-patient or out-patient setting (1:1) to a daily vaginal application of micronized progesterone cream(200 mg)vs. placebo to determine if daily vaginal progesterone administration reduces the risk of preterm birth prior to 34w0d of gestation.

• Study Type: Interventional
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • San Jose, California, United States, 95008
      • Good Samaritan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Gestational age between 20w0d and 24w0d
• Twin pregnancy, diamniotic-dichorionic, both twins living
• Cervical length 10 mm to 25 mm discovered by a screening transvaginal ultrasound exam

Exclusion Criteria:

• Mother less than 18 years of age
• Uterine contractions of 40 seconds duration or more, 10 or more per hour
• Rupture of fetal membranes (leakage of amniotic fluid one or both sacs)
• Ongoing vaginal bleeding

• Any condition likely to cause serious neonatal morbidity independent of gestational age, including:

  1. fetal malformation likely to require surgery
  2. fetal malformation involving vital organs
  3. fetal viral infection
  4. hydrops fetalis
  5. discordance in estimated fetal weight more than 10%
  6. velamentous insertion of umbilical cord of either twin
  7. placenta previa of either placenta
• Any contraindication to continuing the pregnancy
• Cervical cerclage in place or planned

• Any contraindication to vaginal micronized progesterone, including:

  1. Known sensitivity to progesterone or any of the other ingredients
  2. Liver dysfunction or disease
  3. Known or suspected malignancy of breast or genital organs
  4. Active thromboembolic disorder, or history of hormone-associated thromboembolic disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vaginal Progesterone; Daily administration of Vaginal Progesterone (200mg) Gel between 20 weeks of pregnancy and 34 weeks of pregnancy.	Drug: Vaginal Progesterone gel.; Daily administration of Vaginal Progesterone gel in pregnant women with twins between the 20th week of pregnancy and the 34th week of pregnancy.; Other Names: progestin; Procedure: fetal fibronectin swab.; Collection of quantatative fetal fibronectin swab one week after randomization into the trial for both arms. Randomziation occurs between 20 weeks - 24 weeks of gestation.; Other Names: fFN; fibronectin
Placebo Comparator: Placebo; Daily vaginal administration of Placebo gel (Vanicream)between 20 weeks of pregnancy and 34 weeks of pregnancy.	Procedure: fetal fibronectin swab.; Collection of quantatative fetal fibronectin swab one week after randomization into the trial for both arms. Randomziation occurs between 20 weeks - 24 weeks of gestation.; Other Names: fFN; fibronectin; Drug: Placebo gel; weekly vaginal administration of the placebo gel from randomization until 34 weeks of gestation.; Other Names: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Birth of baby before 34 weeks of gestation	The primary outcome is defined as Early Preterm Birth, that is, birth before 34weeks of gestation. A birth at 33weeks 6days or earlier is considered to have the primary outcome. A birth at 34weeks 0days or later does not have the primary outcome. Births for any reason before 34weeks 0days are considered to have the primary outcome, whether they are "spontaneous" or not.	At the time of delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gestational age of baby at birth	measured of the average Gestational age of babies at birth.	measure at time of birth
Rate of "spontaneous birth" before 34weeks of gestation	Rate of "spontaneous birth" before 34weeks of gestation. Spontaneous births are those whose underlying cause is judged to be due to preterm labor, prelabor rupture of membranes, or cervical insufficiency. (In contradistinction, "indicated" deliveries are those due to preeclampsia, fetal growth problems, fetal heart rate abnormalities, and other problems.)	from randomization to birth of the baby - up to 15 weeks
Rate of composite neonatal morbidity	Composite morbidity is defined as any one or more of: stillbirth, neonatal death, infant death before hospital discharge, respiratory distress syndrome (RDS), intracranial hemorrhage (grade 3 or 4)(IVH), necrotizing enterocolitis (stage 2 or 3)(NEC), documented neonatal sepsis within 72 hr of birth, or periventricular leukomalacia (characteristic lesions in the subcortical white matter seen on cerebral imaging studies within 96 hrs of birth)(PVL).	measures from randomization to 60 days post delivery of the baby

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of effectiveness of progesterone in women in highest 2 quartiles of quantitative fetal fibronectin (fFN) versus those in the lowest 2 quartiles of quantitative fFN.	A cervicovaginal swab for quantitative fetal fibronectin testing will be obtained at the first antenatal visit, approximately 1 week after enrollment. The results of this will be used to test a secondary hypothesis that fFN levels will identify a subgroup of participants who respond to progesterone treatment and another subgroup who do not.	from the 21st week of gestation until the 25 week of gestation

Collaborators and Investigators

• Sponsor: Obstetrix Medical Group
• Investigators: Principal Investigator: Andrew Combs, MD, Mednax Center for Research, Education, Quality and Safety

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Anticipated): August 1, 2017
• Study Completion (Anticipated): August 1, 2018

Study Registration Dates

• First Submitted: March 12, 2013
• First Submitted That Met QC Criteria: March 15, 2013
• First Posted (Estimate): March 18, 2013

Study Record Updates

• Last Update Posted (Estimate): December 19, 2014
• Last Update Submitted That Met QC Criteria: December 17, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: short cervix; premature birth; twins
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone; Progestins
• Other Study ID Numbers: OBX0019

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No