Oral Glibenclamide in Preterm Infants with Hyperglycaemia (GALOP)

Assistance Publique - Hôpitaux de Paris

Status and phase: Enrolling; Phase 2

Conditions: Transient; Hypoglycemia, Neonatal; Preterm; Glibenclamide Adverse Reaction

Treatments: Biological: C-peptide proinsulin ratio; Biological: Blood glucose on fluorinated tube; Drug: Glibenclamide; Biological: Pharmacokinetics study; Biological: glycose holter monitor; Biological: Routine biological monitoring

Study type: Interventional

Funder types: Other

Identifiers

NCT05687500

2021-005766-18 (EudraCT Number)

P160916J

Details and patient eligibility

About

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.

Full 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.

Enrollment: 45 estimated patients

Sex: All

Ages: Under 34 weeks old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

45 participants in 1 patient group

Glibenclamide oral

Experimental group

Description:

Amglidia®: glibenclamide oral suspension 6 mg/ml administered by gastric tube after dilution to 1/6th in human milk

Treatment:

Biological: Routine biological monitoring

Biological: glycose holter monitor

Biological: Pharmacokinetics study

Biological: Blood glucose on fluorinated tube

Drug: Glibenclamide

Biological: C-peptide proinsulin ratio