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Oral Glibenclamide in Preterm Infants With Hyperglycaemia (GALOP) (GALOP)

Primary Purpose

Transient; Hypoglycemia, Neonatal, Preterm, Glibenclamide Adverse Reaction

Status
Recruiting
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Glibenclamide
Pharmacokinetics study
C-peptide proinsulin ratio
Blood glucose on fluorinated tube
Routine biological monitoring
glycose holter monitor
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Transient; Hypoglycemia, Neonatal focused on measuring transient hypoglycemia, preterm, glibenclamide

Eligibility Criteria

undefined - 34 Weeks (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hopital Necker - Enfants maladesRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Glibenclamide oral

Arm Description

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

Outcomes

Primary Outcome Measures

Blood glucose control
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

Overall success of the treatment
Overall success of the treatment defined by continuation to the end of treatment without recourse to insulin.
Blood glucose profile on glibenclamide
Time between the start of glibenclamide treatment and the 1st blood glucose < 10 mmol/l
Blood glucose profile on glibenclamide
Time between the start of glibenclamide treatment and the 1st blood glucose < 8 mmol/l
Blood glucose profile on glibenclamide
Proportion of time spent within the target blood glucose range (≥ 4 and < 10 mmol/l) during the period of glibenclamide treatment
Blood glucose profile on glibenclamide
Proportion of time spent above the target level (≥ 10 mmol/l) during the period of glibenclamide treatment
Blood glucose profile on glibenclamide
Proportion of time spent in hypoglycemia (< 2.6 mmol/l) during the period of glibenclamide treatment
Duration of glibenclamide treatment
Duration of glibenclamide treatment.
Nutritional intakes and growth
Carbohydrate
Nutritional intakes and growth:
lipid
Nutritional intakes and growth:
protein
Nutritional intakes and growth:
mean caloric intake (kcal/kg/day) during treatment
Nutritional intakes and growth:
mean weight gain (g/kg/day)
Nutritional intakes and growth
Carbohydrate
Nutritional intakes and growth:
lipid
Nutritional intakes and growth:
protein
Nutritional intakes and growth:
mean caloric intake (kcal/kg/day) during treatment
Nutritional intakes and growth:
mean weight gain ((g/kg/day)
Number of children with episode of hypoglycemia
Number of children with at least one episode of moderate (blood glucose < 2.6 mmol/l) or severe (< 1.5 mmol/l) hypoglycemia
Number of children with episode of hypoglycemia
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
evaluation of the type of adverse reactions identified during the study
Number of adverse reactions on glibenclamide
evaluation of number of adverse reactions identified during the study
Number of participants with co-morbidity
Neonatal morbidity assessed at 36 WA corrected age: intraventricular haemorrhage, periventricular leukomalacia, retinopathy of premature newborns, haemodynamic disorders, ulcerative necrotising enterocolitis
Mortality
Mortality will be assessed
Dose adjustment
Number of dose adjustments, to evaluate the easy of use
ease of use by caregivers
Assessment scores by visual-analogue scale for ease of use by caregivers; 0 as the lowest score, 10 as the highest score
ease of use by caregivers
Assessment scores by visual-analogue scale for ease of use by caregivers; 0 as the lowest score, 10 as the highest score
ease of use by caregivers
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
Evaluated by the pharmacokinetics study
Plasma concentrations of glibenclamide
Evaluated by the pharmacokinetics study
Plasma concentrations of glibenclamide
Evaluated by the pharmacokinetics study
Plasma concentrations of glibenclamide
Evaluated by the pharmacokinetics study
Plasma concentrations of glibenclamide
Evaluated by the pharmacokinetics study

Full Information

First Posted
December 7, 2022
Last Updated
June 14, 2023
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT05687500
Brief Title
Oral Glibenclamide in Preterm Infants With Hyperglycaemia (GALOP)
Acronym
GALOP
Official Title
Oral Glibenclamide in Preterm Infants With Hyperglycaemia (GALOP)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 20, 2023 (Actual)
Primary Completion Date
February 2026 (Anticipated)
Study Completion Date
May 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Transient; Hypoglycemia, Neonatal, Preterm, Glibenclamide Adverse Reaction
Keywords
transient hypoglycemia, preterm, glibenclamide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
45 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Glibenclamide oral
Arm Type
Experimental
Arm Description
Amglidia®: glibenclamide oral suspension 6 mg/ml administered by gastric tube after dilution to 1/6th in human milk
Intervention Type
Drug
Intervention Name(s)
Glibenclamide
Intervention Description
Amglidia®: glibenclamide oral suspension 6 mg/ml administered by gastric tube after dilution to 1/6th in human milk
Intervention Type
Biological
Intervention Name(s)
Pharmacokinetics study
Intervention Description
0.2 ml blood sampling at 3 hours, 6 hours, 10 hours and 24 hours after the first administration and after 24 hours of blood glucose stabilization. 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
Intervention Type
Biological
Intervention Name(s)
C-peptide proinsulin ratio
Intervention Description
blood sampling at before first administration and after 24 hours for measurement of C-peptide proinsulin ratio
Intervention Type
Biological
Intervention Name(s)
Blood glucose on fluorinated tube
Intervention Description
0.3 ml blood sampling at 3 hours, 6 hours, 10 hours and 24 hours after the first administration and after 24 hours of blood glucose stabilization.
Intervention Type
Biological
Intervention Name(s)
Routine biological monitoring
Intervention Description
If there are not performed as part of standard care, biological monitoring of ALT, AST, complete blood count, hemostasis, urea, creatinine, blood ionogram 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.
Intervention Type
Biological
Intervention Name(s)
glycose holter monitor
Intervention Description
glucose levels will be collected with a smarter continuous glucose monitoring system, placed on inclusion and until the end of treatment
Primary Outcome Measure Information:
Title
Blood glucose control
Description
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)
Time Frame
At 72 hours after the first administration
Secondary Outcome Measure Information:
Title
Overall success of the treatment
Description
Overall success of the treatment defined by continuation to the end of treatment without recourse to insulin.
Time Frame
At 36 week of amenorrhea corrected age
Title
Blood glucose profile on glibenclamide
Description
Time between the start of glibenclamide treatment and the 1st blood glucose < 10 mmol/l
Time Frame
At the end of treatment assessed up to 15 days
Title
Blood glucose profile on glibenclamide
Description
Time between the start of glibenclamide treatment and the 1st blood glucose < 8 mmol/l
Time Frame
At the end of treatment assessed up to 15 days
Title
Blood glucose profile on glibenclamide
Description
Proportion of time spent within the target blood glucose range (≥ 4 and < 10 mmol/l) during the period of glibenclamide treatment
Time Frame
At the end of treatment assessed up to 15 days
Title
Blood glucose profile on glibenclamide
Description
Proportion of time spent above the target level (≥ 10 mmol/l) during the period of glibenclamide treatment
Time Frame
At the end of treatment assessed up to 15 days
Title
Blood glucose profile on glibenclamide
Description
Proportion of time spent in hypoglycemia (< 2.6 mmol/l) during the period of glibenclamide treatment
Time Frame
At the end of treatment assessed up to 15 days
Title
Duration of glibenclamide treatment
Description
Duration of glibenclamide treatment.
Time Frame
At the end of treatment assessed up to 15 days
Title
Nutritional intakes and growth
Description
Carbohydrate
Time Frame
At the end of treatment assessed up to 15 days
Title
Nutritional intakes and growth:
Description
lipid
Time Frame
At the end of treatment assessed up to 15 days
Title
Nutritional intakes and growth:
Description
protein
Time Frame
At the end of treatment assessed up to 15 days
Title
Nutritional intakes and growth:
Description
mean caloric intake (kcal/kg/day) during treatment
Time Frame
At the end of treatment assessed up to 15 days
Title
Nutritional intakes and growth:
Description
mean weight gain (g/kg/day)
Time Frame
At the end of treatment assessed up to 15 days
Title
Nutritional intakes and growth
Description
Carbohydrate
Time Frame
At 36 week of amenorrhea corrected age
Title
Nutritional intakes and growth:
Description
lipid
Time Frame
At 36 week of amenorrhea corrected age
Title
Nutritional intakes and growth:
Description
protein
Time Frame
At 36 week of amenorrhea corrected age
Title
Nutritional intakes and growth:
Description
mean caloric intake (kcal/kg/day) during treatment
Time Frame
At 36 week of amenorrhea corrected age
Title
Nutritional intakes and growth:
Description
mean weight gain ((g/kg/day)
Time Frame
At 36 week of amenorrhea corrected age
Title
Number of children with episode of hypoglycemia
Description
Number of children with at least one episode of moderate (blood glucose < 2.6 mmol/l) or severe (< 1.5 mmol/l) hypoglycemia
Time Frame
At 72 hours after first administration
Title
Number of children with episode of hypoglycemia
Description
Number of children with at least one episode of moderate (blood glucose < 2.6 mmol/l) or severe (< 1.5 mmol/l) hypoglycemia
Time Frame
At the end of treatment assessed up to 15 days
Title
Type of adverse reactions on glibenclamide
Description
evaluation of the type of adverse reactions identified during the study
Time Frame
At 36 week of amenorrhea corrected age
Title
Number of adverse reactions on glibenclamide
Description
evaluation of number of adverse reactions identified during the study
Time Frame
At 36 week of amenorrhea corrected age
Title
Number of participants with co-morbidity
Description
Neonatal morbidity assessed at 36 WA corrected age: intraventricular haemorrhage, periventricular leukomalacia, retinopathy of premature newborns, haemodynamic disorders, ulcerative necrotising enterocolitis
Time Frame
At 36 week of amenorrhea corrected age
Title
Mortality
Description
Mortality will be assessed
Time Frame
At 36 week of amenorrhea corrected age
Title
Dose adjustment
Description
Number of dose adjustments, to evaluate the easy of use
Time Frame
At the end of treatment assessed up to 15 days
Title
ease of use by caregivers
Description
Assessment scores by visual-analogue scale for ease of use by caregivers; 0 as the lowest score, 10 as the highest score
Time Frame
At day one of treatment
Title
ease of use by caregivers
Description
Assessment scores by visual-analogue scale for ease of use by caregivers; 0 as the lowest score, 10 as the highest score
Time Frame
At day two of treatment
Title
ease of use by caregivers
Description
Assessment scores by visual-analogue scale for ease of use by caregivers; 0 as the lowest score, 10 as the highest score
Time Frame
At day three of treatment
Title
Plasma concentrations of glibenclamide
Description
Evaluated by the pharmacokinetics study
Time Frame
At 3 hours after the first administration
Title
Plasma concentrations of glibenclamide
Description
Evaluated by the pharmacokinetics study
Time Frame
At 6 hours after the first administration
Title
Plasma concentrations of glibenclamide
Description
Evaluated by the pharmacokinetics study
Time Frame
At 10 hours after the first administration
Title
Plasma concentrations of glibenclamide
Description
Evaluated by the pharmacokinetics study
Time Frame
At 24 hours after the first administration
Title
Plasma concentrations of glibenclamide
Description
Evaluated by the pharmacokinetics study
Time Frame
At 24 hours of blood glucose stabilization

10. Eligibility

Sex
All
Maximum Age & Unit of Time
34 Weeks
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Elsa KERMORVANT, Pr
Phone
01 71 19 61 75
Email
elsa.kermorvant@aphp.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Laure CHOUPEAUX, Master
Phone
01 44 38 17 11
Email
laure.choupeaux@aphp.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacques BELTRAND, Pr
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Michel POLAK
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Delphine MITANCHEZ
Organizational Affiliation
CHRU de Tours
Official's Role
Study Director
Facility Information:
Facility Name
Hopital Necker - Enfants malades
City
Paris
ZIP/Postal Code
75015
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elsa KERMORVANT, Pr
Phone
01 71 19 61 75
Email
elsa.kermorvant@aphp.fr
First Name & Middle Initial & Last Name & Degree
Elsa KERMORVANT, Pr

12. IPD Sharing Statement

Plan to Share IPD
No

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Oral Glibenclamide in Preterm Infants With Hyperglycaemia (GALOP)

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