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

NCT00163020 | Completed Phase 2 Results DMC

• 2 other identifiers: OBX0003OBX 0012
• Study Type: interventional
• Target: 321
• Locations: 1 country
• Sites: 18

Brief Summary

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. 1.Twin pregnancy
2. 2.Triplet pregnancy

Conditions

Preterm Birth

Keywords

Preterm Birth; Preterm Delivery; Multiple gestation; 17-alpha-hydroxyprogesterone caproate; Progesterone

Outcome Measures

Primary Outcomes (10)

• Newborn Respiratory Distress Syndrome (RDS)

  Newborn RDS in the twin arm is defined as compatible symptoms with radiographically confirmed hyaline membrane disease or with respiratory insufficiency of prematurity requiring ventilator support. Data expressed as mean n(%),Odds ratio, CI, and P-value were determined using repeated measures model wherein each twin/triplet within a given pregnancy is considered a repeated measure. Exceptions are comparison with 0 outcomes in one or both groups, so Fisher's Exact Test was used. Morbidity measures were based on live births with data available for the outcomes.

  Measured from delivery until 30 days after baby was discharged from the hospital

• Use of Oxygen Therapy at 28 Days of Newborn Life

  Supplemental oxygen use by the baby measured at the point that the baby reaches 28 days old (after birth)within the twin group.

  Measured at 28 days after birth.

• Newborn Sepsis

  Newborn Sepsis in the twin group was defined as the presence of positive blood culture obtained in the first week of life in association with clinical findings suggesting illness for which the neonate received antibiotics.

  measured during the first week following birth

• Newborn Pneumonia

  Newborn Pneumonia in the twin group is described as compatible symptoms with diagnostic radiograph findings and positive results on blood cultures, persistent leukopenia

  measure during the first 28 days after birth.

• Newborn Intraventricular Hemorrhage Grade 3 or 4

  Newborn Intraventricular hemorrhage (IVH) Stage III in the twin group is described as - IVH with ventricular dilatation. Neonatal Intraventricular hemorrhage (IVH)Stage IV in the twin group is described as - IVH with parenchymal extension.

  measured during the first 28 days after birth

• Newborn Periventricular Leukomalacia (PVL)

  Newborn Periventricular leukomalacia (PVL) in the twin group is described as the presence of more than 1 obvious hypo echoic cyst in the periventricular white matter.

  measured in the first 28 days after birth.

• Newborn Necrotizing Enterocolitis (NEC)Requiring Surgery

  Newborn NEC in the twin group is described as the presence of any of the following: (1)unequivocal intramural air in abdominal radiograph; (2) perforation abdominal radiograph; (3) clinical evidence of perforation (erythema and induration of the abdominal wall or intrabdominal abscess formation); (4) characteristic findings observed at surgery or autopsy; (5) Stricture formation after an episode of suspected necrotizing enterocolitis.

  measured in the first 28 days after birth

• Newborn Retinopathy of Prematurity (ROP)

  Newborn ROP within the twin group is described as retinopathy confirmed on fundoscopic examination, felt to be due to prematurity and subsequent oxygen therapy.

  measured during the first 28 day after birth

• Newborn Asphyxia With Ischemic Injury of Brain, Heart, Kidneys, or Liver

  Newborn Asphyxia or Hypoxic-ischemic encephalopathy (HEI) within the twin group is characterized by clinical and laboratory evidence of acute or subacute brain injury due to asphyxia (ie, hypoxia, acidosis).

  measured during the first 28 days after delivery

• Perinatal Death

  Perinatal death within the twin group is described as a stillbirth, neonatal death, or miscarriage after randomization.

  measured from randomization to 28 days after birth.

Secondary Outcomes (7)

• Individual Components of Neonatal Morbidity (RDS, IVH-III/IV, Bronchopulmonary Dysplasia(BPD), PVL, Sepsis, NEC, ROP-Stage 3/4, Perinatal Death)

  measured as any event noted in the first 28 day following birth.

• Twins: Delivery Prior to 28 Weeks (Wks), 32 Wks, 34wks, and 37 Wks

  Gestational age noted at time of birth

• Triplets: Delivery Prior to 28 Wks, 32 Wks, 35 Wks

  noted at delivery

• Newborn Gestational Age (GA) at Delivery

  determined at the time of birth

• Newborn Birthweight

  measure following delivery

Study Arms (2)

1 Test Group (170HP)

ACTIVE COMPARATOR

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

Drug: 17-alpha-hydroxyprogesterone caproate injectable

2 - Control (Normal Saline)

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

17-alpha-hydroxyprogesterone caproate injectable DRUG

250mg of 17-alpha-hydroxyprogesterone caproate (+ preservatives) injectable weekly starting as early as 19wks gestation until 34.0wks gestation of delivery which ever comes first.

Also known as: 170HP

1 Test Group (170HP)

Placebo DRUG

Weekly doses of placebo (NS + preservatives) via injection as early as 19weeks until 34.0weeks gestation or delivery which ever comes first.

Also known as: Normal Saline

2 - Control (Normal Saline)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Gestational age (GA) 15-23w0d gestational age at the time of recruitment
• GA 16w0dk to 23w6d at the time of randomization and initiation of injections
• Maternal age 18 years or older
• One of these risk factors for spontaneous preterm birth:
• Twins in current pregnancy, dichorionic placentation
• Triplets in current pregnancy, trichorionic placentation
• Intact membranes
• 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.)
• Investigator believes patient will be reliable with follow-up visits and believes that delivery data and neonatal data are likely to be available.

You may not qualify if:

• Symptomatic uterine contractions in current pregnancy
• 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)
• Risk factors for major neonatal morbidity unrelated to preterm delivery (such as monochorionic placentation in multiple gestation, major malformations, certain medication exposures)
• 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.
• Use of progesterone or progesterone-derivative medication after 15 weeks gestation in current pregnancy.
• Allergy to 17OHP or oil vehicle.

Sponsors & Collaborators

• Obstetrix Medical Group: lead

Study Sites (18)

Banner Good Samaritan Hospital

Phoenix, Arizona, 85006, United States

Location

Tucson Medical Center

Tucson, Arizona, 85712, United States

Location

Saddleback Memorial Medical Center

Laguna Hills, California, 92653, United States

Location

Long Beach Memorial Medical Center

Long Beach, California, 90801-1428, United States

Location

University of Southern California-Irvine Medical Center

Orange, California, 92868, United States

Location

Good Samaritan Hospital

San Jose, California, 95124, United States

Location

Swedish Medical Center

Denver, Colorado, 80110, United States

Location

Presbyterian/St Luke's Hospital

Denver, Colorado, 80218, United States

Location

Rose Medical Center

Denver, Colorado, 80220, United States

Location

Skyridge Medical Center

Lonetree, Colorado, 80124, United States

Location

Mercy Medical Center

Des Moines, Iowa, 50314, United States

Location

Saint Luke's Hospital, Kansas City

Kansas City, Missouri, 64111, United States

Location

Erlanger Medical Center

Chattanooga, Tennessee, 37403, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Harris Methodist Fort Worth Hospital

Fort Worth, Texas, 76104, United States

Location

Evergreen Hospital

Kirkland, Washington, 98034, United States

Location

Swedish Medical Center

Seattle, Washington, 98122-4307, United States

Location

Tacoma General Hospital

Tacoma, Washington, 98405, United States

Location

Related Publications (4)

• Goldstein P, Berrier J, Rosen S, Sacks HS, Chalmers TC. A meta-analysis of randomized control trials of progestational agents in pregnancy. Br J Obstet Gynaecol. 1989 Mar;96(3):265-74. doi: 10.1111/j.1471-0528.1989.tb02385.x.

  PMID: 2653414 BACKGROUND

• da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study. Am J Obstet Gynecol. 2003 Feb;188(2):419-24. doi: 10.1067/mob.2003.41.

  PMID: 12592250 BACKGROUND

• Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, Spong CY, Hauth JC, Miodovnik M, Varner MW, Leveno KJ, Caritis SN, Iams JD, Wapner RJ, Conway D, O'Sullivan MJ, Carpenter M, Mercer B, Ramin SM, Thorp JM, Peaceman AM, Gabbe S; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003 Jun 12;348(24):2379-85. doi: 10.1056/NEJMoa035140.

  PMID: 12802023 BACKGROUND

• American College of Obstetricians & Gynecologists. Special problems of multiple gestation. Educational Bulletin 253, 1998.

  BACKGROUND

MeSH Terms

Conditions

Premature Birth

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Kimberly Maurel
• Organization: Obstetrix Medical Group, Inc

kimberly_maurel@pediatrix.com

714-593-9171

Study Officials

• Kimberly Maurel, RN, MSN, CNS

  Obstetrix Medical Group, Inc.

  STUDY DIRECTOR

• Andrew Combs, MD

  Obstetrix Medical Group, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2005
• First Posted: September 13, 2005
• Study Start: November 1, 2004
• Primary Completion: August 1, 2009
• Study Completion: August 1, 2009
• Last Updated: April 11, 2016
• Results First Posted: November 7, 2012

Record last verified: 2016-03

Locations

US (18)