L-Thyroxine Supplementation for Preterm Newborns Less Than 32 Weeks of Gestation With Hypothyroxinemia

L-Thyroxine Supplementation for Preterm Newborns Less Than 32 Weeks of Gestation With Transient Hypothyroxinemia of Prematurity: a Prospective Randomized Double-blind Trial

Transient hypothyroxinemia of prematurity (THOP) is associated with neurodevelopmental impairment in preterm newborns < 32 weeks of gestation (WG). It is not known whether L-Thyroxine supplementation for preterm newborns <32 WG with THOP is beneficial.

The purpose of this study is to compare L-thyroxine treatment vs. placebo in newborn less than 32 WG with THOP.

The primary endpoint is the neurodevelopmental outcome at two years of life, assessed by the Brunet-Lézine score. The secondary endpoints are: death, bronchopulmonary dysplasia (oxygen therapy at 28 days of life and at 36 weeks of postnatal age), patent ductus arteriosus, shock requiring fluid loading or vasoactive treatments, enterocolitis, intraventricular hemorrhage, retinopathy of prematurity, deafness.

Study Overview

• Status: Completed
• Conditions: Hypothyroxinemia
• Intervention / Treatment: Drug: water; Drug: L-Thyroxine

Detailed Description

Preterm newborns <32 weeks of gestation (WG) are screened for THOP between day 5 and day 7 of life. THOP is defined by thyroid-stimulating hormone (TSH) < 20 mIU/L and FT4 < 0.80 ng/dL. After obtaining written consent from the parents, preterm newborns <32 WG with THOP will be included. Randomization is stratified by center and 2 age-groups (24-28 WG and 29-32 WG). One arm will receive L-thyroxine treatment and the other arm will receive placebo. Treatment will be started within one week after diagnosis and will last 6 weeks. TSH and FT4 will be assayed 2 weeks after stopping treatment.

The primary endpoint is the neurodevelopmental outcome at two years of life, assessed by the Brunet-Lézine score.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Basse Normandie
    • Caen, Basse Normandie, France, 14033
      • CAEN University Hospital
  • Nord- Pas De Calais
    • Lens, Nord- Pas De Calais, France, 62307
      • Lens Hospital
  • Picardie
    • Amiens, Picardie, France, 80054
      • Amiens University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 week to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Gestational age < 32 WG
• FT4 (5, 6 or 7 days of life) ≤ 0.8 ng/dL
• TSH (5, 6 or 7 days of life) < 20 mIU/L
• Written consent from the parents

Exclusion Criteria:

• Maternal thyroid disease
• FT4 (5, 6 or 7 days of life) > 0.8 ng/dL
• TSH (5, 6 or 7 days of life) > 20 mIU/L
• Grade III or IV intracerebral hemorrhage

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: water; Oral treatment with water for 6 weeks	Drug: water; Oral treatment with water. Equal number of drop of water as compared with the treatment arm (according to the body weight of the newborn) in the morning, once a day.
Experimental: L-Thyroxine; Oral treatment with L-Thyroxine for 6 weeks	Drug: L-Thyroxine; Treatment with L-Thyroxine:7,5 µg/kg/day. Oral treatment (one drop =5µg) in the morning, once a day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurodevelopmental outcome	Brunet-Lézine score	2 years old

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morbidity associated with management of newborns < 32 WG with hypothyroxinemia	Death; Bronchopulmonary dysplasia (oxygen therapy at 28 days of life and at 36 weeks of postnatal age); Patent ductus arteriosus,; Shock requiring fluid loading or vasoactive treatments; Enterocolitis; Intraventricular hemorrhage; Retinopathy of prematurity; Deafness	discharge, 1 year, 2 years

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire, Amiens
• Investigators: Principal Investigator: Pierre Tourneux, MD, Amiens University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2006
• Primary Completion (Actual): December 31, 2014
• Study Completion (Actual): December 31, 2017

Study Registration Dates

• First Submitted: February 28, 2011
• First Submitted That Met QC Criteria: February 28, 2011
• First Posted (Estimate): March 1, 2011

Study Record Updates

• Last Update Posted (Actual): August 10, 2018
• Last Update Submitted That Met QC Criteria: August 9, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Outcome; Thyroid; Infant, newborn; Infant, preterm; Newborns less than 32 weeks of gestation; TSH < 20 mIU/L and a FT4 < 0.80 ng/dL
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: PHRCIR07-DR-TOURNEUX