Impact of the Administration of Fludrocortisone in Very Premature Infants

NCT03001089 | Completed Phase 2

• 1 other identifier: P150905
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

Water and electrolytic homeostasis is remarkably controlled by the mineralocorticoid pathway (renin-angiotensin-aldosterone system acting on the renal tubule). However, the neonatal period in humans is characterized by a reduced ability of the kidney to ensure normal functions of urine concentration and maintenance of sodium and water balance. This renal functional immaturity, is associated in the very premature infants (VPT) (born \<32 weeks of amenorrhea (SA)) to an immaturity of the adrenal responsible for a default of aldosterone biosynthesis . This relative aldosterone deficiency induces difficulties for VPT to adapt to extra-uterine life when maintaining a positive sodium balance is essential for postnatal growth. The improvement of perinatal care (antenatal corticosteroids maturation, ventilation techniques and use of surfactant) have increased the survival of these children . Nevertheless, extreme prematurity (less than 32 weeks), which concerns nearly 2% of live births in France, remains associated with neurodevelopmental sequelae in nearly 40% of children at 5 years . Secondary hydroelectrolytic disorders with transient mineralocorticoid adrenal insufficiency is probably one of the factors responsible of these neurological deleterious outcomes as well as the occurrence of other complications (bronchopulmonary dysplasia, enterocolitis necrotizing) of extreme prematurity. Indeed, aside from the administration of antenatal steroids to induce maturation, the prevention of postnatal dehydration reduces the risk of intracranial hemorrhage in that population. However, high fluid intake are associated with an increased incidence of patent ductus arteriosus, of bronchopulmonary dysplasia and necrotizing enterocolitis. This necessitates the evaluation of preventive measures to avoid such fluid and electrolyte imbalances by a pharmacological approach based on mineralocorticoid administration in very premature infants, due to the relative aldosterone deficiency identified in this population.

Conditions

Partial Mineralocorticoid Deficiency

Keywords

Neonatology; Endocrinology

Outcome Measures

Primary Outcomes (1)

• Urinary sodium loss evaluated by the urinary ratio Na / creatinine

  Measurement of Na / urinary creatinine ratio at day 3 (evaluating the efficacity of Fludrocortisone action on the kidney by lowering sodium losses, that are very high in very premature infants) by collection of a urinary spot collected on a gauze compress, placed in the diaper of the newborn.

  day 3 (when urinary sodium losses are at their highest in very premature infants)

Secondary Outcomes (14)

• Urinary sodium loss evaluated by the urinary ratio Na / creatinine

  day1, day5, day8, day10 and day15

• urinary sodium and potassium concentrations

  day1,day3, day5, day8, day10 and day15

• plasma sodium and potassium concentrations

  day1, day3, day8 et day15

• plasma renin concentrations

  day1, day3, day8 et day15

• Number of blood tests

  day1,day3, day5, day8, day10 and day15

Study Arms (2)

Fludrocortisone 10 µg tablets

ACTIVE COMPARATOR

Oral Fludrocortisone (enteral) at a dose of 10 mcg 2 times daily (every 12 hours) for 8 days from day 1 (first administration between H24 and H30, and then every 12 hours) until day 8.

Drug: Oral Fludrocortisone (enteral)

placebo oral tablet

PLACEBO COMPARATOR

Oral placebo (enteral) at a dose of 10 mcg 2 times daily (every 12 hours) for 8 days from day 1 (first administration between H24 and H30, and then every 12 hours) until day 8.

Drug: Placebo Oral Tablet

Interventions

Oral Fludrocortisone (enteral) DRUG

Oral Fludrocortisone (enteral) at a dose of 10 mcg 2 times daily (every 12 hours) for 8 days from day 1 (first administration between H24 and H30, and then every 12 hours) until day 8.

Fludrocortisone 10 µg tablets

Placebo Oral Tablet DRUG

oral placebo (enteral) at a dose of 10 mcg 2 times daily (every 12 hours) for 8 days from day 1 (first administration between H24 and H30, and then every 12 hours) until day 8.

placebo oral tablet

Eligibility Criteria

• Age: 26 Weeks - 32 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Very premature newborns defined by a gestational age \<32 and ≥ 26 gestational weeks
• Eutrophic: birth weight between the 10th and 90th percentile of the French reference curves
• Absence of malformations or chromosomal abnormality identified
• Lack of adrenal, pituitary or gonadal diseases diagnosed prior birth
• Lack of participation in another research protocol
• "Inborn": born and hospitalized in the four neonatology departments participating in the study
• Informed consent of the holders of parental authority

You may not qualify if:

• Maternal treatment prior to pregnancy: systemic or inhaled corticosteroids, hormone therapy for adrenal or pituitary insufficiency, antihypertensive treatment (calcium channel blockers, beta blockers, angiotensin)
• Lack or incomplete treatment of antenatal glucocorticoids (betamethasone)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Robert Debré

Paris, 75019, France

Location

MeSH Terms

Interventions

Fludrocortisone

Intervention Hierarchy (Ancestors)

Hydrocortisone; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Martinerie Laetitia, PHD

  APHP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2016
• First Posted: December 22, 2016
• Study Start: June 1, 2017
• Primary Completion: September 8, 2020
• Study Completion: September 8, 2020
• Last Updated: February 16, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)