Multicenter Randomized Trial of Non-inferiority Between Glyburide and Insulin for the Treatment of Gestational Diabetes (INDAO)

Assistance Publique - Hôpitaux de Paris

Status and phase: Completed; Phase 3

Conditions: Diabetes; Gestational

Treatments: Drug: Glyburide; Other: Insulin

Study type: Interventional

Funder types: Other

Identifiers

NCT01731431

P110104

Details and patient eligibility

About

This clinical trial aims to test whether glibenclamide is non-inferior to insulin for the treatment of gestational diabetes.

Full description

In patients with gestational diabetes, a therapeutic treatment with a diet, a blood glucose monitoring and, if necessary, treatment with insulin is associated with reduced neonatal complications. Although the effectiveness of insulin is proven, this therapy has many drawbacks, especially in terms of implementation and monitoring by women. An alternative is the use of oral antidiabetic agents like glibenclamide.

Assumption: Glibenclamide is non-inferior to insulin for the treatment of gestational diabetes.

Main objective: To test the oral Glibenclamide is non-inferior to subcutaneous insulin for the occurrence of perinatal complications in the management of pregnant women developing gestational diabetes and requiring treatment other than dietary.

Secondary Objective: To test the noninferiority of two treatments on maternal glycemic control and maternal complications.

Sample size: With a 80% power and a significance level of 5%, 450 subjects per group are required to show that treatment with glibenclamide is not considered inferior to treatment with insulin if the frequency of outcome composite does not exceed 25% with glibenclamide, whereas it was 18% with insulin (calculated with a non-inferiority margin of 7% and considering that 20% of patients treated with glyburide and Insulin for change half of the patients accept randomization).

Progress of the study: Inclusion of women between 24 and 34 weeks. Randomization between Insulin and Glibenclamide after failure of 10 days of dietary treatment well done. Failure defined by at least 2 abnormal values of glycemia: fasting glucose ≥ 0.95 g / l and/or a postprandial 2h ≥ 1.20 g / l.

Women will receive either insulin according to the usual protocol or Glibenclamide at an initial dose of 2.5 mg / once daily in the morning before breakfast. So long as the glycemic targets will not be reached doses are gradually increased stepwise every 4 days until day 21 (20mg/j) . Patients who have not reached the glycemic targets at this highest dose will have a change in treatment for insulin at day 21. Routine monitoring of pregnant women with gestational diabetes, up to a week after delivery Number of clinical sites: 15 Perspective: Use of Glibenclamide as a first line treatment of gestational diabetes requiring drug treatment.

Enrollment: 914 patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• gestational diabetes diagnosed between 24 and 34 weeks according to international criteria.

Exclusion criteria

• Multiple Pregnancy
• Chronic Hypertension
• Preeclampsia
• Renal impairment
• Hepatic insufficiency
• Long time corticosteroids treatment
• Allergy to sulfa drugs
• Pre-existing diabetes in pregnancy
• Abnormal result on screening test for gestational diabetes before 24SA
• Fasting glucose ≥ 1.26 g / l at initial diagnosis of diabetes
• The need for drug treatment contraindicated or not recommended with taking Glibenclamide
• Poor understanding of French
• Lack of Social Insurance

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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914 participants in 2 patient groups

Insulin

Active Comparator group

Description:

standard protocol of insulin treatment for gestational diabetes

Treatment:

Other: Insulin

Glyburide

Experimental group

Description:

initial dose 2.5 mg per day increased if necessary until 10mg twice a day if glycemia is not controlled

Treatment:

Drug: Glyburide