17OHP for Reduction of Neonatal Morbidity Due to Preterm Birth (PTB) in Twin and Triplet Pregnancies (170HP)

Obstetrix Medical Group

Status and phase: Completed; Phase 3; Phase 2

Conditions: Preterm Birth

Treatments: Drug: Placebo; Drug: 17-alpha-hydroxyprogesterone caproate injectable

Study type: Interventional

Funder types: Industry

Identifiers

NCT00163020

OBX 0012 (Other Identifier)

OBX0003

Details and patient eligibility

About

Hypothesis: Among women with twin or triplet pregnancies, weekly injections of 17-alpha-hydroxyprogesterone caproate (17OHP), started before 24 weeks of gestation, will reduce neonatal morbidity by reducing the rate of preterm delivery.

This study involves two concurrent double-blinded randomized clinical trials of 17OHP versus placebo. Each trial will test the efficacy and safety of 17OHP in women with a specific risk factor for preterm birth. The two risk factors to be studied are:

1. Twin pregnancy
2. Triplet pregnancy

Full description

Prematurity is a leading cause of neonatal morbidity and mortality in the USA. Nationally, 12% of all babies deliver before term and 3% deliver before 32 wks gestational age (GA). Recent studies suggest that 17OHP and other progesterone derivatives may reduce the rate of preterm birth among women with a history of prior preterm birth. However, it has not been demonstrated that this reduction in preterm birth is accompanied by a clinically significant reduction in neonatal complications. Further, most women who deliver preterm have no history of a prior preterm birth. Little is known about whether progesterone treatment is effective in women with other risk factors for preterm birth such as multiple gestation. The proposed study will assess the role of 17OHP in women with twin or triplet pregnancies and will assess the impact on neonatal health, not merely the impact on gestational age at delivery. Prior studies were not designed to be large enough to have statistical power to assess effects on neonatal morbidity.

In the 6 trials combined in the Goldstein meta-analysis, only 279 women were treated with 17OHP and only 73 women had a preterm delivery. The NICHD study presented by Meis approximately doubles the world-wide experience, with 306 women under treatment, of whom 73 delivered prior to 35 wks. Yet, this study was not designed to have power to show a reduction in neonatal complications but only a reduction in preterm birth rates.

The present study is the first to be specifically designed to have adequate power to test whether 17OHP reduces neonatal morbidity among women with one of two specific risk factors for preterm birth.

Enrollment: 321 patients

Sex: Female

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Gestational age (GA) 15-23w0d gestational age at the time of recruitment

2. GA 16w0dk to 23w6d at the time of randomization and initiation of injections

3. Maternal age 18 years or older

4. One of these risk factors for spontaneous preterm birth:

   1. Twins in current pregnancy, dichorionic placentation
   2. Triplets in current pregnancy, trichorionic placentation

5. Intact membranes

6. Patient has had at least one detailed 2nd-trimester ultrasound examination documenting placentation, chorionicity, fetal number, fetal size, amniotic fluid volumes, and fetal anatomy. (This examination must comply with minimum standards such as those published by the American Institute of Ultrasound in Medicine, American College of Radiology, or American College of Obstetricians & Gynecologists It is NOT mandatory that this examination be performed at the research-study center.)

7. Investigator believes patient will be reliable with follow-up visits and believes that delivery data and neonatal data are likely to be available.

Exclusion criteria

1. Symptomatic uterine contractions in current pregnancy
2. Contraindication to interventions intended to prolong the pregnancy (including lethal fetal anomalies, amnionitis, preeclampsia, severe oligohydramnios, severe growth delay, fetal death appears imminent or inevitable)
3. Risk factors for major neonatal morbidity unrelated to preterm delivery (such as monochorionic placentation in multiple gestation, major malformations, certain medication exposures)
4. Preexisting maternal medical condition that might be worsened by progesterone therapy, including: asthma requiring medications, renal insufficiency, seizure disorder, ischemic heart disease, active cholecystitis, impaired liver function, history of thromboembolic disorder, history of breast cancer, history of major depression requiring hospitalization.
5. Preexisting maternal medical condition associated with a high risk of preterm delivery including: refractory hypertension, diabetes with nephropathy or retinopathy, renal insufficiency, active systemic lupus erythematosus. Note that a history of prior preterm birth is NOT an exclusion.
6. Use of progesterone or progesterone-derivative medication after 15 weeks gestation in current pregnancy.
7. Allergy to 17OHP or oil vehicle.
8. Placement of emergent cerclage (defined as one placed after the occurrence of cervical change such as dilation, funneling, or effacement) with this pregnancy. Prophylactic cerclage is NOT an exclusion (defined as one placed before any cervical change, for example, because of a history of cervical incompetence, or because of a prior cervical procedure such as LEEP or cone biopsy).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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321 participants in 2 patient groups, including a placebo group

1 Test Group (170HP)

Active Comparator group

Description:

Test Group will receive weekly doses of 170HP via injection as early as 19weeks until 34.0weeks gestation or delivery which ever comes first.

Treatment:

Drug: 17-alpha-hydroxyprogesterone caproate injectable

2 - Control (Normal Saline)

Placebo Comparator group

Description:

Control Group will receive weekly doses of placebo (NS) via injection as early as 19weeks until 34.0weeks gestation or delivery which ever comes first.

Treatment:

Drug: Placebo