Organization of Teratology Information Services (OTIS) Autoimmune Diseases in Pregnancy Project

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00116272
First received: June 28, 2005
Last updated: August 19, 2015
Last verified: August 2015
  Purpose
The purpose of the study is to evaluate the effect of etanercept when used in the first trimester of pregnancy with respect to major structural birth defects of newborns. This is an observational study only - no investigational product is used.

Condition Intervention
Pregnancy
Drug: Etanercept

Study Type: Observational
Study Design: Observational Model: Cohort
Official Title: OTIS Autoimmune Diseases in Pregnancy Project

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Percentage of Infants With Major Birth Defects in Pregnancies Ending With Live-born Infants [ Time Frame: From birth through 1 year of age ] [ Designated as safety issue: No ]
    A major structural defect is defined as a defect which has either cosmetic or functional significance to the child (e.g., a cleft lip). The Registry used the Metropolitan Atlanta Congenital Defects Program (MACDP) birth defect classification system, with some specified modifications that are appropriate for cohort studies as opposed to case-control studies.

  • Percentage of Infants With Major Birth Defects in All Pregnancies [ Time Frame: From birth through 1 year of age ] [ Designated as safety issue: No ]
    A major structural defect is defined as a defect which has either cosmetic or functional significance to the child (e.g., a cleft lip). The Registry used the Metropolitan Atlanta Congenital Defects Program (MACDP) birth defect classification system, with some specified modifications that are appropriate for cohort studies as opposed to case-control studies.


Secondary Outcome Measures:
  • Percentage of Infants With Any 3 or More Minor Birth Defects [ Time Frame: From birth through 1 year of age ] [ Designated as safety issue: No ]
    A minor structural defect is defined as a defect which occurs in less than 4 percent of the population but which has neither cosmetic nor functional significance to the child (e.g., complete 2,3 syndactyly of the toes). The Registry used the Metropolitan Atlanta Congenital Defects Program (MACDP) birth defect classification system, with some specified modifications that are appropriate for cohort studies as opposed to case-control studies.

  • Percentage of Infants With a Specific Pattern of Any 3 or More Minor Birth Defects [ Time Frame: From birth through 1 year of age ] [ Designated as safety issue: No ]
    A minor structural defect is defined as a defect which occurs in less than 4 percent of the population but which has neither cosmetic nor functional significance to the child (e.g., complete 2,3 syndactyly of the toes). A pattern is defined as at least the same 3 specific minor malformations occurring in at least two infants in the exposed group.

  • Percentage of Pregnancies Ending in Spontaneous Abortion [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    Computed using Kaplan-Meier estimate at 20 weeks gestation, accounting for left truncation due to varying time in gestation at enrollment. In multiple pregnancies ending in at least 1 live-born infant, the live birth outcome is included in the analysis. In multiples ending in no live birth outcomes, the spontaneous abortion is counted as 1 event.

  • Percentage of Participants With Pre-term Delivery [ Time Frame: 9 months ] [ Designated as safety issue: No ]
    A pretem delivery is defined as prior to 37 weeks gestation. Computed using Kaplan-Meier estimate at 37 weeks' gestation, accounting for left truncation due to varying time in gestation at enrollment. Multiple births are excluded.

  • Gestational Age at Delivery (GAD) of Live Births [ Time Frame: At birth ] [ Designated as safety issue: No ]
  • Birth Weight Among Full Term Infants [ Time Frame: At birth ] [ Designated as safety issue: No ]
  • Birth Length Among Full Term Infants [ Time Frame: At birth ] [ Designated as safety issue: No ]
  • Birth Head Circumference Among Full Term Infants [ Time Frame: At birth ] [ Designated as safety issue: No ]
  • Percentage of Infants With Small for Gestational Age Birth Weight [ Time Frame: At birth ] [ Designated as safety issue: No ]
    Small for gestational age is defined as ≤ 10th percentile for sex and gestational age using National Center for Health Statistics (NCHS) / Center for Disease Control (CDC) growth curves.

  • Percentage of Infants With Small for Gestational Age Birth Length [ Time Frame: At birth ] [ Designated as safety issue: No ]
    Small for gestational age is defined as ≤ 10th percentile for sex and gestational age using National Center for Health Statistics (NCHS) / Center for Disease Control (CDC) growth curves.

  • Percentage of Infants With Small for Gestational Age Birth Head Circumference [ Time Frame: At birth ] [ Designated as safety issue: No ]
    Small for gestational age is defined as ≤ 10th percentile for sex and gestational age using National Center for Health Statistics (NCHS) / Center for Disease Control (CDC) growth curves.

  • Postnatal Weight Percentile at One Year [ Time Frame: 1 year after birth ] [ Designated as safety issue: No ]
  • Postnatal Length Percentile at One Year [ Time Frame: 1 year after birth ] [ Designated as safety issue: No ]
  • Postnatal Head Circumference Percentile at One Year [ Time Frame: 1 year after birth ] [ Designated as safety issue: No ]
  • Percentage of Infants at One Year of Age With Small for Gestational Age Weight [ Time Frame: 1 year after birth ] [ Designated as safety issue: No ]
    Postnatal growth deficiency defined as ≤ 10th centile for chronological age. Age adjusted for gestational age at delivery if child was less than 12 months of age at postnatal measurement, unadjusted if ≥ 12 months of age at postnatal measurement.

  • Percentage of Infants at One Year of Age With Small for Gestational Age Length [ Time Frame: 1 year after birth ] [ Designated as safety issue: No ]
    Postnatal growth deficiency defined as ≤ 10th centile for chronological age. Age adjusted for gestational age at delivery if child was less than 12 months of age at postnatal measurement, unadjusted if ≥ 12 months of age at postnatal measurement.

  • Percentage of Infants at One Year of Age With Small for Gestational Age Head Circumference [ Time Frame: 1 year after birth ] [ Designated as safety issue: No ]
    Postnatal growth deficiency defined as ≤ 10th centile for chronological age. Age adjusted for gestational age at delivery if child was less than 12 months of age at postnatal measurement, unadjusted if ≥ 12 months of age at postnatal measurement.

  • Percentage of Infants With Reported Serious or Opportunistic Infections Through One Year [ Time Frame: From birth to 1 year ] [ Designated as safety issue: No ]
  • Percentage of Infants Diagnosed With Any Malignancy Through One Year of Age [ Time Frame: From birth to 1 year ] [ Designated as safety issue: No ]
  • Percentage of Infants With Abnormal Results on Ages and Stages Questionnaire (ASQ) [ Time Frame: 1 year after birth ] [ Designated as safety issue: No ]
    The ASQ-3 evaluates 5 domains of development: communication, gross motor, fine motor, problem solving, and personal-social. Each domain has a set of 6 items and parents rate the most appropriate answer for the presence of each skill: "Yes," "Sometimes," "Not Yet," with point values of 10, 5, or 0, respectively. Each domain question set is totaled independently and compared against statistically derived cutoffs that are set at 2 standard deviations below the mean. The percentage of infants below the cut-off or close to the cutoff (borderline) is reported.


Biospecimen Retention:   None Retained
This is a prospective & observational, exposure cohort study

Enrollment: 830
Study Start Date: April 2005
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Etanercept-Exposed
Pregnant women with a current diagnosis of rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), ankylosing spondylitis (AS), psoriatic arthritis (PsoA) or psoriasis (PsO) who used etanercept in the first trimester of pregnancy for any length of time.
Drug: Etanercept
Pregnant women previously exposed to etanercept during the first trimester. Etanercept was not administered in this non-interventional study.
Other Name: Enbrel
Diseased Controls
Pregnant women with a current diagnosis of RA, JRA, AS, PsA, or PsO who did not use etanercept or any tumor necrosis factor (TNF) antagonist during pregnancy.
Non-Diseased Historical Comparison
Pregnant women not diagnosed with RA, JRA, AS, PsoA, or PsO who did not use etanercept or any TNF antagonist at any time in pregnancy and were not exposed to any known human teratogen during pregnancy. This cohort consists of historical controls enrolled in other pregnancy outcome studies selected to match pregnant women in the exposed cohort.

Detailed Description:

This pregnancy registry cohort study will be conducted by the Organization of Teratology Information Specialists (OTIS) which is a network of university and health department based telephone information centers serving pregnant women and health care providers throughout North America.

Participants in the first two cohorts are recruited concurrently from callers to OTIS centers, from health care providers and through direct to consumer marketing efforts. The source of historical controls is archived data on pregnancies that have been followed through the California Teratogen Information Service's Clinical Research Program located at the University of California San Diego.

  Eligibility

Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Cohort 1: Exposure Cohort (300 subjects) Cohort 2: Matched diseased control Cohort (300 subjects) Cohort 3: Non-diseased Control Cohort (300 subjects)
Criteria

Cohort 1 Inclusion Criteria: Eligible subjects will be currently pregnant women residing in the US or Canada who have had any exposure to etanercept for treatment of Rheumatoid Arthritis (RA), Juvenile RA, Ankylosing Spondylitis (AS), Psoriatic Arthritis (PsoA) or Psoriasis (PsO) at any time during the first trimester of pregnancy which is defined as the period between first day of the last menstrual period (i.e., within two weeks of conception) up to and including the 12th week after the first day of the last menstrual period (LMP) - Eligible subjects must have documentation of an exposure to etanercept during the first trimester of pregnancy.

Cohort 2 Inclusion Criteria: Eligible subjects will be currently pregnant women residing in the US or Canada who have not taken etanercept or any TNF antagonist for treatment of RA, JRA, AS, PsoA or PsO at any time in the current pregnancy or within two months prior to the first day of the last menstrual period (LMP).

Cohort 3 Inclusion Criteria: Eligible subjects will be pregnant women who were residing in the US or Canada who had not been diagnosed with RA, JRA, AS, PsoA or PsO and had not been exposed to a known human teratogen during the index pregnancy.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00116272

Locations
United States, California
Research Site
San Diego, California, United States
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00116272     History of Changes
Obsolete Identifiers: NCT01017016
Other Study ID Numbers: 20040246 
Study First Received: June 28, 2005
Results First Received: May 29, 2015
Last Updated: August 19, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Amgen:
pregnancy
Autoimmune Disease

Additional relevant MeSH terms:
Autoimmune Diseases
Immune System Diseases
Etanercept
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antirheumatic Agents
Gastrointestinal Agents
Immunologic Factors
Immunosuppressive Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Sensory System Agents

ClinicalTrials.gov processed this record on May 25, 2016