Oral Glibenclamide in Preterm Infants with Hyperglycaemia (GALOP)

Phase 2

Recruiting

• Conditions: Transient; Hypoglycemia, Neonatal; Preterm; Glibenclamide Adverse Reaction
• Interventions: Drug: Glibenclamide; Biological: Pharmacokinetics study; Biological: C-peptide proinsulin ratio; Biological: Blood glucose on fluorinated tube; Biological: Routine biological monitoring; Biological: glycose holter monitor

• Registration Number: NCT05687500
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Study Timeline

• Study First Submitted: 2022-12-07
• Study First Submitted QC: 2023-01-06
• Study First Posted: 2023-01-18
• Study Start: 2023-05-20
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-17
• Last Update Posted: 2025-01-20
• Primary Completion: 2026-11-20
• Study Completion: 2027-02-20

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 45

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Glibenclamide oral	Glibenclamide	Amglidia®: glibenclamide oral suspension 6 mg/ml administered by gastric tube after dilution to 1/6th in human milk
Glibenclamide oral	Pharmacokinetics study	Amglidia®: glibenclamide oral suspension 6 mg/ml administered by gastric tube after dilution to 1/6th in human milk
Glibenclamide oral	C-peptide proinsulin ratio	Amglidia®: glibenclamide oral suspension 6 mg/ml administered by gastric tube after dilution to 1/6th in human milk
Glibenclamide oral	Blood glucose on fluorinated tube	Amglidia®: glibenclamide oral suspension 6 mg/ml administered by gastric tube after dilution to 1/6th in human milk
Glibenclamide oral	glycose holter monitor	Amglidia®: glibenclamide oral suspension 6 mg/ml administered by gastric tube after dilution to 1/6th in human milk
Glibenclamide oral	Routine biological monitoring	Amglidia®: glibenclamide oral suspension 6 mg/ml administered by gastric tube after dilution to 1/6th in human milk

Primary Outcome Measures

Name	Time	Method
Blood glucose control	At 72 hours after the first administration	The primary evaluation criteria is 72 hours blood glucose control on glibenclamide treatment (success of the treatment). This is defined as the non-use of insulin and absence of severe hypoglycemia (\< 1.5 mmol/l) or persistent moderate hypoglycemia (\< 2.6 mmol/l in 2 successive measurements (dextro) at an interval of more than 3 hours)

Secondary Outcome Measures

Name	Time	Method
Nutritional intakes and growth	At 36 week of amenorrhea corrected age	Carbohydrate
Overall success of the treatment	At 36 week of amenorrhea corrected age	Overall success of the treatment defined by continuation to the end of treatment without recourse to insulin.
Duration of glibenclamide treatment	At the end of treatment assessed up to 15 days	Duration of glibenclamide treatment.
Blood glucose profile on glibenclamide	At the end of treatment assessed up to 15 days	Proportion of time spent in hypoglycemia (\< 2.6 mmol/l) during the period of glibenclamide treatment
Nutritional intakes and growth:	At 36 week of amenorrhea corrected age	mean weight gain ((g/kg/day)
Number of adverse reactions on glibenclamide	At 36 week of amenorrhea corrected age	evaluation of number of adverse reactions identified during the study
Number of children with episode of hypoglycemia	At the end of treatment assessed up to 15 days	Number of children with at least one episode of moderate (blood glucose \< 2.6 mmol/l) or severe (\< 1.5 mmol/l) hypoglycemia
Type of adverse reactions on glibenclamide	At 36 week of amenorrhea corrected age	evaluation of the type of adverse reactions identified during the study
Number of participants with co-morbidity	At 36 week of amenorrhea corrected age	Neonatal morbidity assessed at 36 WA corrected age: intraventricular haemorrhage, periventricular leukomalacia, retinopathy of premature newborns, haemodynamic disorders, ulcerative necrotising enterocolitis
Dose adjustment	At the end of treatment assessed up to 15 days	Number of dose adjustments, to evaluate the easy of use
ease of use by caregivers	At day three of treatment	Assessment scores by visual-analogue scale for ease of use by caregivers; 0 as the lowest score, 10 as the highest score
Plasma concentrations of glibenclamide	At 24 hours of blood glucose stabilization	Evaluated by the pharmacokinetics study
Mortality	At 36 week of amenorrhea corrected age	Mortality will be assessed

Trial Locations

Locations (1)

Hopital Necker - Enfants malades; 🇫🇷 Paris, France