RecruitingPhase 2NCT05687500

Oral Glibenclamide in Preterm Infants With Hyperglycaemia (GALOP)


Sponsor

Assistance Publique - Hôpitaux de Paris

Enrollment

35 participants

Start Date

May 20, 2023

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Max Age: 34 Weeks

Inclusion Criteria8

  • 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 Criteria12

  • 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

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Interventions

DRUGGlibenclamide

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

BIOLOGICALPharmacokinetics study

* For the first 10 patients during the test phase, four 0.2 ml samples will be taken at H3, H6, H10, and H24 (+/- 1 hour) after the first dose; an additional sample will be taken for patients whose blood sugar levels stabilize beyond 24 hours, after 6 hours of stable blood sugar levels (4-10 mmol/l); * For subsequent patients included during phase II: * 1 sample of 0.2 ml within the first 24 hours of treatment, during a care assessment. * 1 sample of 0.2 ml within the first 24 hours of treatment, during a care assessment * 1 sample of 0.2 ml per day at each daily check-up as part of care during the treatment period. * In centers that are unable to perform the samples and the appropriate techniques for centralizing these PK points, these samples will not be taken. PK parameters of glibenclamide will be determined using nonlinear analysis: area under the plasma concentration time curve (AUC), absorption constant, apparent clearance and volume of distribution.

BIOLOGICALC-peptide proinsulin ratio

blood sampling at before first administration and after 24 hours for measurement of C-peptide proinsulin ratio if it is impossible to collect both volumes, the C-peptide collection will be prioritized

BIOLOGICALRoutine biological monitoring

If there are not performed as part of standard care, biological monitoring of ALT, AST, complete blood count, hemostasis, urea, creatinine, blood ionogram, total bilirubin and conjugated bilirubin will be done before first administration at the following time frame : 48 hours after the first administration than each days during treatment period, and 48 hours after the end of treatment. Transaminases and hemostasis will be done only in case of clinical indication before the first administration.


Locations(1)

Hopital Necker - Enfants malades

Paris, France

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NCT05687500


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