Clinical trial NCT05687500: Oral Glibenclamide in Preterm Infants with Hyperglycaemia (GALOP)
Official title: Oral Glibenclamide in Preterm Infants with Hyperglycaemia (GALOP)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Transient; Hypoglycemia, Neonatal
Preterm
Glibenclamide Adverse Reaction
Keywords: transient hypoglycemia
preterm
glibenclamide
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2023-01-18
Enrollment: 45
Sex: ALL
Maximum age (years): 34
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to confirm hypothesis that Glibenclamide can be administered orally and is an alternative to insulin therapy in treating transient hyperglycemia of premature newborns.

Detailed description: Transient hyperglycemia of premature newborns results from an overall decrease in insulin sensitivity, which is responsible at the beta cell level for abnormalities of intragranular cleavage of proinsulin into insulin, leading to reduced active insulin secretion. Intravenous administration of exogenous insulin can be used to combat insulin resistance and lower blood glucose, but it is difficult to manage in premature newborns and is associated with a substantial risk of hypoglycemia. Glibenclamide, which stimulates endogenous insulin secretion and can be administered orally, might be an alternative to insulin therapy in treating transient hyperglycemia of premature newborns.

Eligibility criteria: Inclusion Criteria:

* Newborn less than 34 week of amenorrhea corrected age
* Birth weight \< 1500 g
* Birth term \< 32 week of amenorrhea
* Hyperglycemia ≥ 10 mmol/l in 2 measurements, 3 hours apart after potential reduction of glucose intakes following each department's protocol
* Secure venous access point (umbilical venous catheter or epicutaneo-cava catheter)
* Enteral feeding considered before inclusion or already established
* Consent obtained from persons holding parental authority
* Beneficiary of social security

Exclusion Criteria

* Contraindication to enteral feeding (at the discretion of the clinician responsible for the child)
* Contraindication to glibenclamide according to current SPC
* Foetal growth restriction (FGR) birth weight \< 3rd percentile (AUDIPOG definition)
* Severe birth defect, including cardiac malformation associated with a risk of myocardial ischemia
* Severe sepsis requiring mechanical ventilation or haemodynamic support
* Severe renal dysfunction (serum creatinine \> 120 µmol/l)
* Severe hepatocellular failure (V factor less than the standard laboratory range for the age) and/or severe cholestasis (\> 50 µmol/L)
* Hyperglycemia associated with an error in administering glucose infusion
* Profound hypophosphoremia (\< 1 mmol/l)
* Hypersensitivity to glibenclamide or other sulphonylureas or sulphonamides, or one of the excipients
* Patient with continuous insulin IV administration
* Patient treated with miconazole

Primary outcomes:
measure: Blood glucose control
timeFrame: At 72 hours after the first administration
Secondary outcomes:
measure: Overall success of the treatment
timeFrame: At 36 week of amenorrhea corrected age
measure: Blood glucose profile on glibenclamide
timeFrame: At the end of treatment assessed up to 15 days
measure: Blood glucose profile on glibenclamide
timeFrame: At the end of treatment assessed up to 15 days
measure: Blood glucose profile on glibenclamide
timeFrame: At the end of treatment assessed up to 15 days
measure: Blood glucose profile on glibenclamide
timeFrame: At the end of treatment assessed up to 15 days
measure: Blood glucose profile on glibenclamide
timeFrame: At the end of treatment assessed up to 15 days
measure: Duration of glibenclamide treatment
timeFrame: At the end of treatment assessed up to 15 days
measure: Nutritional intakes and growth
timeFrame: At the end of treatment assessed up to 15 days
measure: Nutritional intakes and growth:
timeFrame: At the end of treatment assessed up to 15 days
measure: Nutritional intakes and growth:
timeFrame: At the end of treatment assessed up to 15 days
measure: Nutritional intakes and growth:
timeFrame: At the end of treatment assessed up to 15 days
measure: Nutritional intakes and growth:
timeFrame: At the end of treatment assessed up to 15 days
measure: Nutritional intakes and growth
timeFrame: At 36 week of amenorrhea corrected age
measure: Nutritional intakes and growth:
timeFrame: At 36 week of amenorrhea corrected age
measure: Nutritional intakes and growth:
timeFrame: At 36 week of amenorrhea corrected age
measure: Nutritional intakes and growth:
timeFrame: At 36 week of amenorrhea corrected age
measure: Nutritional intakes and growth:
timeFrame: At 36 week of amenorrhea corrected age
measure: Number of children with episode of hypoglycemia
timeFrame: At 72 hours after first administration
measure: Number of children with episode of hypoglycemia
timeFrame: At the end of treatment assessed up to 15 days
measure: Type of adverse reactions on glibenclamide
timeFrame: At 36 week of amenorrhea corrected age
measure: Number of adverse reactions on glibenclamide
timeFrame: At 36 week of amenorrhea corrected age
measure: Number of participants with co-morbidity
timeFrame: At 36 week of amenorrhea corrected age
measure: Mortality
timeFrame: At 36 week of amenorrhea corrected age
measure: Dose adjustment
timeFrame: At the end of treatment assessed up to 15 days
measure: ease of use by caregivers
timeFrame: At day one of treatment
measure: ease of use by caregivers
timeFrame: At day two of treatment
measure: ease of use by caregivers
timeFrame: At day three of treatment
measure: Plasma concentrations of glibenclamide
timeFrame: At 3 hours after the first administration
measure: Plasma concentrations of glibenclamide
timeFrame: At 6 hours after the first administration
measure: Plasma concentrations of glibenclamide
timeFrame: At 10 hours after the first administration
measure: Plasma concentrations of glibenclamide
timeFrame: At 24 hours after the first administration
measure: Plasma concentrations of glibenclamide
timeFrame: At 24 hours of blood glucose stabilization
Other outcomes:
Locations:
city: Paris
country: France
facility: Hopital Necker - Enfants malades
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Jacques BELTRAND, Pr
role: STUDY_DIRECTOR
affiliation: Assistance Publique - Hôpitaux de Paris
name: Michel POLAK
role: STUDY_DIRECTOR
affiliation: CHRU de Tours
name: Delphine MITANCHEZ
role: STUDY_DIRECTOR
References: