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Phase 3 N=1,203 Randomized Triple-blind Treatment

Thyroid Therapy for Mild Thyroid Deficiency in Pregnancy

Subclinical Hypothyroidism · Hypothyroxinemia · Pregnancy

Enrolled (actual)
1,203
Serious AEs
0.9%
Results posted
Jan 2019
Primary outcome: Primary: Intellectual Function of Children at 5 Years of Age in Women Diagnosed With a) Subclinical Hypothyroidism or b) Hypothyroxinemia During the First Half of Pregnancy, or Death. — 97; 94; 94; 91 score on a scale — p=0.71

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Levothyroxine (Drug); Placebo for Levothyroxine (Drug)
Age
Pediatric, Adult, Older Adult
Sex
Female
Sponsor
The George Washington University Biostatistics Center
Primary completion
Aug 2015

Outcome Measures

OutcomeResultp-value
PRIMARY
Intellectual Function of Children at 5 Years of Age in Women Diagnosed With a) Subclinical Hypothyroidism or b) Hypothyroxinemia During the First Half of Pregnancy, or Death.
97; 94; 94; 91 0.71
SECONDARY
Week of Gestation at Delivery
39.1; 38.9; 39.0; 38.8 0.57
SECONDARY
Number of Participants With Preterm Delivery
9; 10; 10; 7; 31; 37 0.81
SECONDARY
Selected Cognitive Abilities From the Subscales of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III)
97; 95; 94; 92 0.89
SECONDARY
Cognitive and Achievement Levels From the Differential Ability Scales (DAS II)
90; 90; 90; 89 0.90
SECONDARY
Cognitive and Achievement Levels From Two DAS-II Subtests (Recall of Digits Forward and Recognition of Pictures)
84; 84; 91; 74; 74; 74 0.60
SECONDARY
Cognitive, Motor and Language Scale Scores From the Bayley Certified Scales of Infant Development III Edition
100; 100; 100; 100; 97; 97 0.63
SECONDARY
Behavioral Problems and Social Competencies at 36 and 60 Months of Age, as Measured by the Child Behavior Checklist (CBCL)
46; 46; 48; 48; 44; 44 0.99
SECONDARY
Attention Deficit Hyperactivity Disorder (ADHD) Index Score From the Connors' Rating Scales (Parent-S) - Revised
48; 49; 50; 49 0.37
SECONDARY
Participants With Placental Abruption
1; 5; 3; 2 0.12
SECONDARY
Participants With Gestational Hypertension
33; 36; 20; 24 0.69
SECONDARY
Participants With Preeclampsia
22; 20; 9; 11 0.76
SECONDARY
Gestational Diabetes Mellitus
25; 22; 21; 24 0.66
SECONDARY
Participants With Composite Neonatal Outcome
7; 12; 5; 7 0.24
SECONDARY
Participants Who Experienced a Stillbirth or Miscarriage
4; 7; 2; 5 0.36
SECONDARY
Number of Neonatal Deaths
0; 1; 1; 1 0.50
SECONDARY
Number of Infants With Apgar Score 4 at 1 Minute and < 7 at 5 Minutes
6; 7; 6; 7; 2; 3 0.76
SECONDARY
Number of Infants Admitted to NICU
29; 21; 31; 31 0.24
SECONDARY
Infants With Birth Weight < 10th Percentile (Gestational Age z Score)
33; 27; 23; 20 0.45
SECONDARY
Neonatal Head Circumference (Centimeters)
33.9; 33.9; 33.9; 34.2 0.46
SECONDARY
Number of Infants With Respiratory Distress Syndrome
9; 6; 4; 5 0.45
SECONDARY
Number of Infants With Retinopathy or Prematurity
1; 0; 0; 0 1.00
SECONDARY
Number of Infants With Necrotizing Enterocolitis
1; 1; 2; 0 1.00
SECONDARY
Number of Infants With Bronchopulmonary Dysplasia
0; 1; 0; 1 0.50
SECONDARY
Number of Infants With Respiratory Therapy Greater Than or Equal to 1 Day
11; 11; 13; 12 0.99
SECONDARY
Number of Days in the Hospital Nursery
2; 2; 2; 2 0.43

Summary

The purpose of this study is to determine whether treating women, who are diagnosed with a mild imbalance of thyroid hormones during pregnancy, with thyroid hormone replacement affects their children's intellectual development at 5 years of age.

Eligibility Criteria

Inclusion Criteria

  • Subclinical Hypothyroidism as defined by an elevated TSH (≥ 3.00 mU/L) and a free-T4 in the normal range (i.e. 0.86 to 1.90 ng/dL) or Hypothyroxinemia as defined by a TSH in the normal range (0.08 to 2.99 micrometers (mU)/L) and a low free-T4 (<0.86 ng/dL)
  • Singleton Pregnancy
  • Gestational age at randomization between 8 weeks 0 days and 20 weeks 6 days

Exclusion Criteria

  • Major fetal anomaly or demise
  • Planned termination of the pregnancy
  • History of thyroid cancer or current thyroid disease requiring medication
  • Diabetes, on medication (insulin, glyburide)
  • Collagen vascular disease (autoimmune disease), such as lupus, scleroderma and polymyalgia rheumatica, on medication
  • Receiving anticoagulant therapy
  • Depression, currently on treatment with tricyclics or selective serotonin reuptake inhibitors (SSRIs)
  • Other known serious maternal medical complications including:
  • Chronic hypertension requiring antihypertensive medication (including diuretics)
  • Epilepsy or other seizure disorder, on medication
  • Active or chronic liver disease (acute hepatitis, chronic active hepatitis) with persistently abnormal liver enzymes
  • Cancer (including melanoma but excluding other skin cancers)
  • Heart disease (tachyrhythmia, class II or greater heart disease or on heart medication). Mitral valve prolapse without arrhythmia is not an exclusion.
  • Asthma, on oral corticosteroids
  • Known illicit drug or alcohol abuse during current pregnancy
  • Delivery at a non-network hospital
  • Participation in another intervention study that influences maternal and fetal morbidity and mortality, or participation in this trial in a previous pregnancy
  • Unwilling or unable to commit to 5 year follow-up of the infant
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00388297). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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